Hope in Focus Brings Voices of People Living with LCA Directly to the FDA

Allison Wolf, whose 9-year-old son Elliot lives with the encroaching blindness of Leber congenital amaurosis (LCA), spoke directly to staff from the country’s regulatory agency to help them understand the dire need for treatments for the rare inherited retinal disease.

“Elliot’s eyes are dying, Allison said. “They are dying, and we have nothing to help slow down the progressive loss of his eyesight,” she told the Foo d and Drug Administration (FDA).

“What would a timely and effective treatment mean? The whole world,” the mother of four said.

Allison and five others affected by LCA shared their stories with the FDA during a recent Patient Listening Session hosted by Hope in Focus.

We brought together the voices of people living with LCA, caregivers, and a clinician treating people with LCA to FDA staff members in a 90-minute online meeting Oct. 30, 2023. Simply put, we wanted the FDA to truly hear our community’s voices.

Our year-long planning resulted in a successful session to help regulators understand patient/caregiver experiences related to LCA. We requested the meeting to raise awareness with FDA staff about clinical differences of LCA genotypes, share patient experiences of LCA’s impact on the quality of their lives, given the scarcity of treatments, and communicate the extraordinary significance of vision stabilization for patients.

Raising awareness is key to advancing research

People in our community struggle daily to find ways to cope and try to live normal lives in a sighted world. Still, they never give up hope for new treatments and the possibility of a cure. As an advocacy organization, one of our biggest challenges is creating awareness of LCA.

Courtney Coates, our Director of Outreach and Development, introduced the Hope in Focus mission and said LCA affects about one in 33,000 people and presents early in life, resulting in total blindness. Twenty-seven genes have been identified to cause LCA, with treatment available for one form, while a handful of others are in clinical trials.

Co-founder and Board Chair Laura Manfre said as the parent and caregiver of their daughter Sofia living with LCA, raising awareness, searching out new treatments, and providing support to the growing LCA community became the mission of Hope in Focus.

Laura said she wanted to underscore the goals of treatment, in particular around the stabilization of vision for Sofia and others with LCA.

“While vision restoration would be fantastic, having access to a treatment that stabilizes her vision would be huge for her. Not having to constantly change her accommodations for her changing vision is a huge win, and not having to fall asleep every night worried that the next morning might be the one she wakes up without any vision at all. That would be life changing.”

Sharing a chart showing seven current clinical trials, she explained two are not recruiting at this time, two have been discontinued, and all seven represented only four LCA genetic variations.

“So, there is still a lot of work to be done to advance potential treatments.”

Caregivers and people living with LCA tell their stories

Six people from our community shared their experiences.

Elliot Wolf wearing red glasses and a red shirt — Elliot Wolf

Allison Wolf, who is 45 and from North Dakota, said doctors diagnosed her son Elliot with LCA13 (RDH12) when he was 6, and as he gets older, her challenges also grow.

“Nobody knows how to raise a visually impaired child. I must be taught. I must teach him the sighted world, while also dealing with the challenge of teaching him the non-sighted world,” she told agency staff. “My heart hurts when I hear Elliot say, ‘I just want to be done with all this work and I just want to play.’”

***

Mohamed Farid of Illinois is a 36-year-old entrepreneur, diagnosed with LCA5 at 40 days old. His mother quit her job to take care of him, and they moved back to Egypt. Preserving his sight concerns him the most, and his greatest fear is the risk of injury.

“For new treatments,” Mohamed told the FDA, “the first thing I would look for is something to stop any degradation – I sense that my functional vision has degraded slightly over time and would imagine there is something going on with my retina, but do not know.

I have been told by doctors that I will lose my sight in the next two to three years ever since I was 5, and that lack of a prognosis is a killer. Following conservation, I care most about night blindness, then field of vision. …

“I was lucky to have a huge support network of people, who went out of their way and had a lot of energy and stress tolerance. This does not mean that life was easy or that I would not want a cure, even a partial cure would be life changing. It does mean that the cost of LCA is high, but barely bearable.”

***

Joy Goodwine, 40, of New York is the mother of 7-year-old Jordynn, diagnosed at age 1 with LCA2 (RPE65), and received a new diagnosis last year of LCA1 (GUCY2D). She always wanted Jordynn to have some sense of normalcy.

Jordynn Erwin in pink dress with a hot pink background — Jordynn Erwin

“I’ve always asked family and friends to treat her like any other child,” Joy said. “I do not want people to feel sorry for her and I do not want her to have any special treatment because of her

visual impairment. Jordynn is being raised to know that she is capable of doing anything she wants with limitations…

“What I fear most as a parent with a child living with LCA is I worry that her kindness and vulnerability will lead to unwanted interactions when she gets old enough to go off on her own, or her eyes get worse if treatment is not available.”

***

Linda Wirth is 76 and lives in Colorado. Her vision loss remained a mystery until her diagnosis of LCA10 (CEP290) at age 68. As a child, she learned about the world around her by touching things and holding them.

“My family often told me, ‘Don’t touch that! You will break it. Don’t act strange. People will stare at you.’ So, I began to fake it, pretending I understood things which I did not in order to get along and not appear any different.”

One doctor early on told her: “You are blind! What do you want me to tell you? If you are looking for a miracle, there is none.”

A retired clinical social worker, Linda’s been angrily dismissed from jury duty and job interviews, ignored by waitstaff, and questioned whether she deserved to be a parent.

“Just as many differently abled folks, I have encountered individuals with various stereotypes and prejudices.”

***

DJ Broadbin of Connecticut is a 34-year-old mother and caregiver to 5-year-old Jace, who was diagnosed with LCA4 (AIPL1) at 10 months old. Through a Hope in Focus connection, she succeeded in getting compassionate use treatment in the UK for Jace. The treatment, which applied only to his specific gene mutation, has restored some of his sight in one eye.

“No matter what happens with his vision or developing new treatments,” DJ told the FDA, “I remain steadfast in having the same goal I had for Jace since the very second I found out I was going to be a mom – I just want him to be happy. And I will continue to fight for his inclusion in this world to make sure that he always is.”

She often finds herself exhausted by the constant stress of being a caregiver.

“I also wish sometimes,” DJ said as her voice broke, “I just got to be a mom. Not a medical coordinator, an occupational therapist, and a Teacher of the Visually Impaired all rolled up into one. Just mom.

“But then I think about all the things that Jace’s diagnosis has given me personally: Clarity. Patience. Compassion and empathy in a way that I myself was too blind to see in those earlier days.”

***

Mirielle St. Arnaud is 16 and lives in Illinois. She was diagnosed with LCA (IQCB1/NPHP5) at 6 months old. Her early diagnosis was possible because her older brother had been diagnosed with LCA.

Mirielle worries about her safety and struggles to fit in with her classmates because she misses social cues. She hopes her fairly stable vision will not get worse.

She shared a wish list with the FDA that included personal independence, the opportunity to participate in sports, and more certainty about achieving the career of her choice (she dreams of being a lawyer).

“Some of the more significant challenges I face because of visual impairment relate to jobs and getting hired. It takes longer for me to learn certain skills at a job. I have to rely on others when out in public, especially when traveling. I also struggle to find accommodations for my impairment. It seems that other people know my needs better than I do.”

***

Our representative clinician, Rachel M. Huckfeldt, MD, PhD, of Massachusetts Eye & Ear, spoke about the difficulties of diagnosing and managing LCA and the small number of clinical trials. Identifying the responsible genes can be difficult, and the small number of patients severely limits opportunities for clinical trials.

Questions asked by FDA staff members focused on a few common themes: Have you participated in clinical trials? What are the key impediments to clinical trial participation? What are your deal-breakers to participation? What would a successful treatment look like to you?

One result certainly not on the agenda was the deep emotional impact of the stories shared by those living with LCA and caregivers. The session manifested itself as a profoundly moving event.

A full summary of the FDA Patient Listening Session will be available on our website.

Plans in the Works for Connecticut’s New Rare Disease Advisory Council and 2023 Rare Disease Day

Advocates for people living with rare diseases are collaborating with Connecticut Gov. Ned Lamont’s office and leaders of the Connecticut General Assembly’s Public Health Committee to build the state’s new Rare Disease Advisory Council (RDAC) that requires appointees, budgets, and bylaws be in place this summer.

Assistant Director of Advocacy for the National Organization for Rare Disorders (NORD) Kristin Angell joined Co-Ambassadors Katie Gillick and Lesley Bennett of NORD’s Connecticut Rare Action Network (CT-RAN) in hosting a Zoom conference with more than 30 people, including state legislators, patient advocates, doctors, researchers, industry leaders, health care providers, caregivers, and people living with rare disease.

The meeting included two representatives from Connecticut-based Hope in Focus and discussions about the range of needs to be addressed by the new council and the planning of next month’s celebration of Rare Disease Day on Feb. 28.

“We are working on it, and we will get it done,” Bennett said.

A rare disease is defined as one affecting fewer than 200,000 people nationwide. More than 7,000 known rare diseases affect an estimated one in 10 people in the United States, translating to about 30 million people or 10 percent of the country’s population. Globally, 300 million people live with rare diseases.

With the establishment of a permanent Connecticut RDAC, 13 members will be appointed to advise and make recommendations to the Department of Public Health, the Department of Social Services, and other state agencies about the needs of people living in Connecticut with a rare disease and their caregivers. Advisory councils may differ from state to state. Please click here to check whether your state has an RDAC or is working to establish one.

Hope in Focus, in its advocacy for people living with Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs), helped generate awareness of the need for an RDAC and for the legislation to make it happen.

The cause of many rare diseases is unknown, but about 80 percent are genetic, such as LCA and other IRDs, and about half of all rare diseases affect children.

Getting state agencies to understand the rare disease population is key to the RDAC. Even something as simple as putting links to national rare disease resources on state government departments’ websites would be a big step.

More than 40 people submitted applications to become part of Connecticut’s council, and six have been appointed so far. The names of the new members will be announced when all 13 have been appointed.

The group will include insurance, public health, and social services commissioners, or their designees, and 10 members appointed by the Governor and the Public Health Committee leadership.
Those 10 members will be:

a representative of an association of hospitals or a hospital administrator, and a physician with expertise in medical genetics
a representative of a patient advocacy group in the state representing all rare diseases, and a family member or caregiver of a pediatric patient living with a rare disease
a representative of the biopharmaceutical industry involved in rare disease research and therapy development, and an adult living with a rare disease
a member of the scientific community engaged in rare disease research, and a caregiver of a child or adult living with a rare disease
a physician who treats people living with a rare disease, and a representative, family member, or caregiver of a person living with a rare disease

Planning for Rare Disease Day

Following the midterm elections and changes in some legislative seats at Connecticut’s General Assembly, educating lawmakers is key to finding solutions for people living with rare disease to have the necessary access, resources, and educational tools to enjoy their best quality of life.

One person attending the meeting talked about the need for more doctors and patient advocates in Connecticut because people living with rare disease often must travel to another state for medical care. She also mentioned the potential of patients being charged for sending simple questions to doctors through computer health care portals, and whether lawmakers attending upcoming Rare Disease Day events could help mitigate or eliminate those costs.

Please share any ideas to help raise awareness for Rare Disease Day and your thoughts on bringing Connecticut’s RDAC to fruition by getting in touch with Kristin Angell at kangell@rarediseases.org, Katie Gillick at katie.gillick@rareaction.org, or Lesley Bennett at lesley.bennett@rareaction.org.

NORD and CT-RAN plan another meeting later this month to discuss updates on the RDAC and Rare Disease Day.

Let’s Chat About … Self-Advocacy and Supporting Your Child’s Education with Beth Borysewicz

Children living with visual impairment become more independent and empowered when parents set high expectations for their kids and challenge them every day.

Just ask Beth Borysewicz. In her role with Connecticut’s Bureau of Education Services for the Blind, she makes a living helping children with visual disabilities realize their potential as strong, self-determined adults. And she’s the first one to say, often with tears in her eyes, that her job is to work herself out of a job.

Beth Borysewicz

She described her work in helping children from birth to 22 years old with visual impairment or blindness become more independent as adults as part of the Hope in Focus “Let’s Chat About …” webinar series. Our March episode, moderated by Courtney Coates, Director of Outreach and Development, featured Borysewicz, an Education Consultant for the Department of Aging and Disabilities, Bureau of Education Services for the Blind.

We developed the series with those living with Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs) in mind, but we invite all members of our community, including those in research, industry, and the regulatory communities to join any of the sessions, as we look ahead to a common goal of advancing treatments for rare retinal disease. Click here to view this episode.

Borysewicz found her passion working with the blind and low-vision community unexpectedly 16 years ago, when she had a 3-year-old student named Sofia, who was diagnosed with LCA. Yes, that would be the same Sofia as in Sofia Sees Hope, our organization’s original name until a recent rebranding to Hope in Focus. Borysewicz also is Vice Chair of our Board of Directors.

She said parents need to be the biggest advocates for their children.

“If you think your child is not getting what they need, you can ask for it.”

She also encouraged connections with people who have been on this journey before, bringing to mind the Hope in Focus Family Connections program that helps ease feelings of isolation that can arise when a family member is diagnosed with a rare disease.

“It’s the people that have already gone through it who will help you the most, including Hope in Focus. That’s why I’m on the board. What Hope in Focus does for families is immeasurable.”

All the Little Things We Do Every Day

As a Teacher of Students with Visual Impairments (TVI), Borysewicz focuses on teaching students self-advocacy and exploring the Expanded Core Curriculum (E.C.C.), distinguished from a school’s standard core curriculum consisting of courses in math, science, reading, and the like.

E.C.C. comes from the perspective of teaching students with blindness or low-vision and encompasses nine areas: Compensatory Skills, Orientation and Mobility, Social Interaction, Independent Living, Recreation and Leisure, Sensory Efficiency, Assistive Technology, Career Education, and Self-Determination.

The curriculum is more than a checklist or lesson plans for learners with a visual impairment, according to The E.C.C. and Me website. It’s all the little things we do every day, done with intention so children with visual impairments can learn skills they need for a fulfilling life.

“I wish everyone would do what I do,” Borysewicz told her webinar audience. “There is a shortage worldwide of TVIs.”

She advised parents to set expectations high for their children, challenge them every day, and give them a safe place to learn.

“Children can do anything they set their minds to. Do anything you can do to empower them,” she said. “Celebrate everything. Celebrate every little thing.”

She talked about self-determination, saying it’s her favorite part of the curriculum and the most important.

“It’s teaching a child to believe in themselves and just take that leap,” she said. “It’s taking that step off the curb to cross the street with a cane or initiating a conversation at a lunch table that builds self-confidence.”

Making Learning Fun and Exciting

Her work with people from birth to age 22 encompasses figuring out resources for newly diagnosed children, for school-aged students, and for young adults transitioning to the workforce or college.

“I switch hats from appointment to appointment every day,” she said. “As you can tell, I love my job.”

Working with individualized education plans (IEP), she and her team helps students become the best they can be in all the E.C.C. areas.

“It’s so important for the student to say, ‘This is what I need and why I need it,’ and just building those skills will make them successful as adults.”

And a lot of it is fun, especially with Borysewicz who excels in the Recreation and Leisure department. It goes back to when she was growing up and her dad always told her she was good at playing with people and should get a degree in play.

She implements that play degree often by creating board games to make math more fun or putting together programs to help students from prekindergarten through grade 3 explore the nine E.C.C. areas in their daily lives.

In an Expedition to Explore, students in the Young Passport Program worked on accumulating life skills at home over the summer. Each student has a passport consisting of pages designated for each of the nine E.C.C. areas, with a slant toward adventure. For example, “Career Education Caves” focuses on conversational skills, encouraging children to stay connected with their friends over the summer, known in the business world as networking, and holding mock interviews with their siblings or stuffed animals.

In “Self-Determination Safari,” a goal is to get the child to ask for help. A parent asks a child to do an unfamiliar chore, such as taking out the trash or putting toys away but doesn’t give guidance on how to do it or where to put the trash or toys, prompting or encouraging the child to ask for assistance or directions.

“Social Skills Glaciers” encourages children to spread kindness to neighbors and the community and recommends an online guide called “100 Acts of K i ndness for Kids.” Activities include listening, following directions, taking turns, ignoring distractions, cooperating, and showing empathy. (Sounds great for adults, too!)

Resources for People with Blindness or Low Vision

Borysewicz talked about her work from the perspective of Connecticut and said services may differ from state to state.

She authors a blog dedicated to professionals, families, and students called I Love Brl (Braille) and she provided webinar viewers this list of resources:

9 More than Core; The Independent Little Bee; Expanded Core Curriculum Ideas for Preschoolers and Early Elementary; Is My Child Getting a Quality V1 Program?; Integrating E.C.C. Activities into Literacy Instruction; Family Connect; and Wonder Baby.

Our New Name – FAQs

Why did we change our name?

It’s simple: we’ve grown and matured as an organization. And we’re looking ahead to how we can best position this organization for the future. We were never about one individual – we’ve always been for all of the Sofias – all the individuals, all the families, and all the genetic variants associated with LCA. The new name has simply evolved to reflect that.

Why change the name now?

The pandemic gave us an unintentional break from normal operations, kind of like many of us since early 2020. Unable to plan and go forward with public events, such as our Dinner in the Dark gala fundraiser and our LCA Family Conference, we had time to work on a new name.

Who decided to change the name?

Our President and Co-Founder Laura Manfre has been thinking about changing the name for a long time. Researchers asked her and her family to fundraise when she learned of Sofia’s genetic LCA diagnosis in 2012. She and others founded Sofia Sees Hope in 2014 to advocate and raise funds for all in the LCA and IRD communities, and Sofia came to represent all Sofias. The organization was founded to be inclusive, and we are now updating the name to reflect that inclusivity.

Has anything else about the organization changed?

Nope. Our mission is the same; only our name has changed, and we hope this will better position us to grow and extend the reach of our work and focus.

Why did we work with a branding firm?

We’ve come to know a lot about rare inherited retinal diseases, genetic testing, clinical trials, federal drug approval, 27 different forms of LCA, and tons more about rare inherited retinal diseases, but we needed professional help in the branding department.

We found that help through an old friend, Bonnie Southcott, who has been with us since the beginning and knows our people and our mission. She also is Director of Patient Engagement at Toolhouse, a digital marketing firm in the life sciences sector.

She describes the essence of rebranding or renaming as carefully identifying a brand’s DNA and then capturing it in the new words, look, and feel of the name, the logo, and the tagline. The three-month process involved our founders, board members, staff, donors, and the people we connect with in the LCA and IRD communities. We think she did a great job and hope you do, too!

How was the rebranding funded?

We are very fortunate to have generous supporters who donated their significant talent, and their time to our rebranding initiative. For the expenses we did incur, these were covered with grant funding designated for administrative expenses and capacity building as we position our organization for the future.

It is important to us that contributions received from individual donors are used solely for the benefit of research and genetic testing. Meanwhile, our education, outreach, and advocacy programs, as well as our capacity-building activities and administrative expenses are supported by grants and restricted contributions designated for those activities.

What does Sofia think about the name change?

She is excited for the update! She has always known that the organization’s mission was to serve the broader community, and she looks forward to continuing her involvement, which has included everything from leading a book club for middle schoolers to supporting fundraising to representing the organization at partner events.

Will Dinner in the Dark return?

YES! And here is the date to save: Saturday, October 8, 2022, at the Mystic Marriott in Groton, Connecticut. We cannot wait to gather safely again, for this, and for other in-person events like our LCA Family Conference, A Rare Opportunity, and more.

Sofia Sees Hope Rebrands with an Eye to the Future

Sofia Sees Hope this month unveiled a new name and logo — Hope in Focus — as the organization sets its course for the next decade of work to benefit the Leber congenital amaurosis (LCA) community.

Embracing and encompassing, Hope in Focus is our new name: Embracing because research advancements fuel hope and ease feelings of isolation that often accompany a rare-disease diagnosis, and encompassing because our global advocacy reaches all of those living with LCA and other rare inherited retinal diseases (IRDs).

Our organizational namesake, Sofia, was a little girl with LCA in 2014. She has now come of age, and so have we. Throughout the last seven years, Sofia Sees Hope has transformed from a small NPO into a robust, international organization, and that’s why we’ve taken the exciting step of evolving our name while keeping hope as its centerpiece.

“Hope is built on the bedrock of yearning; not an unrequited yearning, but the yearning for what we know can be,” President and Co-Founder Laura Manfre said. “Hope is fuel, driving us to action. It binds us together and soothes our souls when darkness falls. Hope is our Polaris; the brightest star in the IRD constellation.”

Hope also is empowering and a strong motivator. It is the role of Hope in Focus to make sure we hear those voices of the patients, families, and community, and we help craft compassionate, forward-thinking policy.

“Without hope there is not a chance you’re going to advance treatment,” Manfre said. “We cannot sit back and wait for it like manna from heaven because that’s just not going to work.”

Why The Name Change?

As Sofia Sees Hope grew from its beginnings, so did its reach geographically and genetically with those living with LCA and IRDs. The development and 2017 federal approval of LUXTURNA®, a vision-restoring gene therapy, marked an incredible milestone in the rare retinal disease world. Several factors powered the name change.

Sofia Sees Hope established steady grant funding and strong corporate partnerships over the years to support advocacy programs, such as our LCA Family Conferences, quarterly newsletter, and monthly webinars.

“We are grateful to our grantors and corporate partners, and, for the most part, that funding has remained steady and that’s what we use for outreach and for continuing to build a sustainable organization,” Manfre said.

Our advocacy group forged vital relationships with global organizations like Foundation Fighting Blindness and Retina International and with pharmaceutical and biotechnology companies, resulting in remarkable research advancements. These include improved access to genetic testing and the development of more than 30 clinical trials into retinal disease research.

“We’ve reached this level of organizational maturity where we’re well-known enough that we can manage a name change and continue to provide even better service to the community,” Manfre said. “We are well-positioned for the future and believe this name change will only help us to be more successful.”

Unintentional Opportunity of Time

Manfre said she didn’t necessarily want her daughter’s name attached to the organization because from the beginning it was about so much more than her. After Sofia received her confirmed genetic diagnosis of the gene causing her vision loss — IQCB1 — her family was asked to fundraise.

“Every year I would step back and question it. Is it time to change our name? It was never about Sofia specifically,” she said. “Since our incorporation, we provided funding to support a variety of research initiatives, including My Retina Tracker® Program.”

But then the COVID-19 pandemic set in, giving an unintentional opportunity to press the pause button for time to re-evaluate.

“COVID gave us time, although that’s not how we would have wanted to do it.” The name Sofia Sees Hope served our organization well once we established we were reaching out to people like Manfre’s daughter, Sofia, and people living with any one of the 27 known forms of LCA and a host of IRDs.

Now in the eighth year since our founding, research has advanced exponentially, and we wanted to be clear that we are there for the whole LCA and IRD community” she said.

“We are not changing who we are or what we do. We’re just changing the name.” Manfre said the name change also relieves the pressure on Sofia that comes with having her name be part of the organization. Sofia has supported at fundraisers, educational events, and most recently by leading a book club for middle schoolers with LCA and other visual impairments.

The Process Behind Our New Name

We had amazing help with finding the right name. Bonnie Southcott led the three-month project. Southcott is former Director of Patient Engagement at Toolhouse, a digital marketing firm in the life sciences sector, based in Washington state. Under her guidance, we developed a new name, Hope in Focus, a new tagline, “Seeing a cure for blindness,” and a new logo.

“I think it’s important to know that the organization itself hasn’t changed. The (new) name is more reflective of the greatest audience that they serve and of their vision for the future,” she said. “The other piece of it is that it takes away one of the questions, and that question was ‘Who’s Sofia?’ ”

Sofia represented people with LCA, but some might not get that and think twice before reaching out to our organization, thinking, ‘I don’t know who Sofia is, the organization might not be right for me.’

“That only has to happen once to have an impact,” Southcott said. “To take away that question was key.”

She describes the essence of rebranding or renaming as carefully identifying a brand’s DNA and then capturing it in the new words, look, and feel of the name, the logo, and the tagline. By involving representatives from each stakeholder group and planning a careful rollout, she said, the organization’s supporters, constituents, and staff become champions of the reimagined brand.

“Hope: That was almost like a life raft that people jumped into. You have to focus on hope. It is too central for what this organization stands for.”

The name also reflects the human connection the organization makes with the LCA and IRD communities: “The warm embrace that Hope in Focus stands for.” The name also differentiated our group nicely from others in the field and that’s important for messaging, important for fundraising, and important for growth, she said.

“Some do offer that sense of hope, but you don’t get that from the name. The new name really had to convey that, and it had to underscore that the purpose is not only Sofia, but all the Sofias. “The hope component — that sets us apart.”

Science and research comprised the other piece folding into the mix, thinking about microscopes and getting a clearer focus on treatments and cures, especially with one gene therapy on the market and more developing research in clinical trials.

Southcott and her colleague Chance Martenson began with 40 possibilities for names and narrowed them to 12 after conversations with our founders, board members, staff, donors, and the people we connect with in the LCA and IRD communities. From there, they recommended three for consideration.

The name change or rebrand of our organization stood out among other projects she has done. “It was more an evolution of what existed, as opposed to a revolution or the creation of something brand new, where nothing existed before.”

Finding the right name also meant not disenfranchising people involved with our advocacy group. “There is this real sense of dedication to the organization and a yearning to protect it from anything else, Southcott said. At the end of the day, it had to serve the people that support it and use it.”

Our Future

We at Hope in Focus will expand the reach in our advocacy efforts and continue to grow as a small team doing big things, Manfre said. The vision for Hope in Focus is far reaching, and we are developing exciting ways to engage our community members and bring them together as we support them, and they support one another.

“We’ve been powered by a small team of part-time consultants and volunteers, and we’ve just recently
brought on board a full-time development and outreach director,” Manfre said. “To be able to continue to expand to meet the needs and the demands of the LCA and IRD communities, we need to keep growing. I view this as the first step in that growth.

“We’re checking all the boxes, working to fill unmet needs. This is much bigger than me and much bigger than Sofia. We only began something that is going to continue to grow, and we’re very excited about where it will go.”

Let’s Chat About … Patient Registries and My Retina Tracker

Join the My Retina Tracker® registry and you’ll be contributing to science by driving research to help improve your quality of life and to find treatments and cures for Leber congenital amaurosis (LCA) and other rare inherited retinal diseases (IRDs).

The free and secure online registry launched six years ago by the Foundation Fighting Blindness is being updated and your feedback is needed. The organization currently is conducting a “user-experience” survey of its membership to glean new ideas to make the registry more effective for patients and for researchers, according to the Foundation’s Todd Durham.

Now, through at least the end of June, you can contribute by taking the survey on the registry’s website and updating your profile. If you’re not already part of the registry, click here to join. The global registry has more than 18,000 members and is open to anyone with an inherited retinal condition and/or adult caregivers of children.

As the Foundation’s Vice President of Clinical & Outcomes Research, Durham is responsible for directing the organization’s Clinical Consortium of retinal experts, developing strategies to enhance product development, partnering with industry, and providing technical input on partnered programs and investment decisions.

The Foundation is the world’s leading private funder of retinal disease research and collaborates with patients, caregivers, researchers, and biopharmaceutical companies. That funding has been a driving force behind the progress toward cures, including the identification of more than 270 genes linked to retinal disease, and the launch of 42 clinical trials for potential treatments.

Durham discussed the patient registry and survey in our May webinar episode: “Let’s Chat About … Patient Registries and My Retina Tracker®.” Sofia Sees Hope Director of Marketing and Communications Elissa Bass moderates the free monthly webinar series. You can watch the webinar here.

Durham earned a Bachelor of Science in Public Health, a master’s in biostatistics, and a PhD in health policy and management (Decision Science and Outcomes Research) from the University of North Carolina School of Global Public Health. He has more than 25 years of drug-development experience.

Understanding Patients and Retinal Disease Through Data

A patient registry is a planned collection of data around a disease. My Retina Tracker distinguishes itself from others by focusing on inherited retinal degenerations or diseases with the purpose to understand genetics, prevalence of conditions, and impacts of IRDs on individuals’ lives.

The registry also enables researchers to find people for clinical trials, especially challenging work in the rare disease world of LCA and other IRDs.

Registry subsections include assistive devices, driving, visual symptoms, and the recently added “My Health Today,” a series of questions developed by the National Institutes of Health (NIH) to assess physical and mental health.

To become a member, click on ‘Register Now’ and follow the prompts to establish a username and password and to answer questions to build your personalized retinal health profile. You are then guided through a series of questionnaires developed by retinal clinicians, geneticists, genetic counselors, and rare inherited retinal disease researchers.

The registry becomes your personal retinal health record, updated by you and your doctors. Your history and testing results create a critical resource in tracking the progress of your disease and becoming part of a comprehensive database. It employs state-of-the-art technology to protect privacy and adheres to the highest standards of confidentiality and ethics.

Your disease information is accessible only to you, Foundation registry staff, and researchers who meet a rigorous scientific review application process to use the data for studies and to reach individuals to participate in clinical trials, Natural History studies, or focus groups. Your personal information is never shared with researchers.

It’s important to update your profile because the data unique to those living with LCA and other IRDs gives researchers a trove of opportunities for studies. The more complete the profile, the more likely you are to be contacted about a research opportunity.

“Many of our research collaborators may approach us with a research idea and a certain criterion they want to apply to their study, and we use as much data in the profile as we can to help find the right target for that study,” Durham said. “As your vision changes, as your life situation changes, we’d like to know the milestones along the way. That’s informative information.”

Enhancing Patient Registries through Survey Feedback

An important improvement to the registry would be the ability to highlight to its members the research emanating from the information given by registrants. Completing the survey and giving specific feedback will help accomplish this.

“The key focus right now is delivering back to the members some information that they find useful, that shows that they are contributing to science.”

The Foundation also wants to engage its registry membership more regularly with information tailored to profiles.

“Speaking with a number of individuals involved with the Foundation, they say ‘it sure would be nice if when I tell you that my gene is, let’s say, EYS that you could tell me more about people like me.’ We’re looking into some ways that we can collect that data, put it in a way that’s understandable, digestible, presentable, and make that available to our membership, the registry.”

Results from the user-experience survey will be central in making the registry more valuable.

“As much as possible we really want folks’ feedback and, in this survey, we ask about their experience not just with the registry itself, but also with our genetic testing program, which many people have been able to take advantage of.

“We’re in a rapidly evolving research field; we’ve got new therapies coming all the time. To me, it’s important to put in mechanisms where we can learn along the way, and we’ll want to get as many indicators as possible.”

Patient Registries: Making a Difference Through Research

Every month, six or seven researchers contact the Foundation for access to the registry, Durham said. One proposed study would look at patient experience with genetic testing and counseling.

“How did that counseling session change the way they view their life, what impact did it have on them? This is very promising and interesting research. When we saw this, we thought this is very relevant for our members and for our community in general because we believe genetic testing is hugely important.

“From my conversations with individuals, that moment when you have the clarity of a genetic diagnosis is kind of a day that you remember. It is now the time where I can at least ask the question, ‘what is the typical progression for folks like me? Are there research opportunities for me? What are the research prospects for people like me?’

“All this research can make a big impact.”

One project using registry data produced an analysis estimating the cost of illness for an IRD – an economic burden of up to $31.7 billion in the United States.

“When you see the paper as to the estimated cost to the U.S. of the IRDs, that study result came because people participated in the My Retina Tracker registry.”

The Foundation plans to prepare reports or peer-reviewed publications out of the registry over the coming years to show the research community how much can be learned about what life is like with an IRD.

Patient Registries Put People at the Center of Research

The registry also is an integral part of patient-focused drug development, a national concept organized by the U.S. Food and Drug Administration to put patients at the center of research.

“This is a unique thing that the Foundation is doing to make sure we don’t lose sight that there are humans, there are people and lives that are impacted by research.”

In a partnership as part of this patient-focused research, Sofia Sees Hope and the Foundation conducted intensive workshops on the CRB1 and IQCB1 genes that included the voices and perspectives of patients and their families, along with dozens of leading experts.

Another example of patient-centered research is the collaboration between the Foundation and the biopharmaceutical industry to study males with X-linked retinitis pigmentosa (XLRP), an incurable genetic disease that causes blindness in men and affects about one in 15,000 people.

“We’ll be surveying people through our registry and then convening a panel of experts and inviting the FDA to attend a workshop about results of the work and also inviting affected individuals and their caregivers to tell us what life is like with XLRP,” Durham said.

Living in a Time of Hope

Retinal research has come far, with more than 40 clinical trials underway.

“This is an exciting time, and I don’t think it’s an exaggeration to say, which should be a great time of hope, because 10 years ago there were not a whole lot of treatments to talk about,” he said, “and now even as the Foundation stands, we struggle to keep up with all the latest news amongst therapy developers.”

Not all therapies work out, but researchers learn a lot in the process of product development.

Also, conditions once thought to have been impossible to treat now have multiple therapeutic approaches, with even more in the pipeline.

Durham said, for example, neuroprotection, which is the relative preservation of neuronal structure and/or function, and neuroprosthetics,* implantable medical devices that provide some degree of vision to people with blindness.

“If we can just slow down the further degeneration of the photo receptors that could be really helpful, that could add hopefully years to vision. Gene therapy has the potential in many cases to restore vision that was lost. And you have even new technologies for later-stage disease, like (visual) neuroprosthetics.

“It’s pretty amazing technology that’s coming out.”

Sofia Sees Hope Scavenger Hunt

Welcome to the Sofia Sees Hope Scavenger Hunt! We are glad to meet you.

We are doing this to continue to raise awareness for rare inherited retinal disease and Leber congenital amaurosis, which is challenging during a global viral pandemic. We launched it last year because of the coronavirus crisis, when in-person fundraising went dark and we were unable to be with our family and friends in person. It was so fun that we are bringing it back this year, even as COVID restrictions are being lifted in many places. As always, we ask that you adhere to your local requirements, and practice social distancing and mask wearing where required or prudent.

Your entry fee will benefit Sofia Sees Hope, and the education, outreach and advocacy work we are engaged in. We will also make a donation from the entry fees to a 501(c)3 nonprofit of the winner’s choosing (up to $250)! This way you can help a charity in your community that is also doing important work.

Questions? Email us at info@sofiaseeshope.org

How it works

The Scavenger Hunt is open to anyone around the world! The maximum number you can have on your team is 5 (five) but they don’t all have to live in the same house! This could be a fun way to stay in touch with friends or family.

The only equipment you’ll need is a smart phone that can take photos/videos and a Facebook account.

To be officially entered, you must fill out this Google form. Once we receive your entry, you will be emailed confirmation and a link to make your suggested minimum team donation of $100. (Here’s the official rules, etc. you need to know.)

Sofia Sees Hope Scavenger Hunt poster info

The Scavenger Hunt runs from Friday, May 21 through Monday, May 31. On opening day, you will receive an email with the list of challenges. You must complete 10 (ten) of the challenges by 11:59 p.m. EST Monday, May 31 to be entered into the pool to win.

There will be 2 additional requirements in the game:

To begin, at least ONE member of each team must complete a quiz about rare disease. You will receive a link to the quiz in the confirmation email.
On the last day, Wednesday, May 20, at least ONE member of each team must share 3 facts about Leber congenital amaurosis or rare disease on their Facebook, Instagram or Twitter and tag Sofia Sees Hope (@sofiaseeshope on all platforms). It can be 3 facts included in 1 post, or 3 separate posts.

You will post all your photos and/or videos in this Facebook group as you complete challenges. Once you are confirmed as entered in the hunt, you will be invited to join the Facebook group. The group is private, meaning that no one outside it can see who is a member, or any of the posts.

And the winner is …

Every team that completes 10 challenges by the hunt’s end will be entered into a random drawing for the winner.

The winner will be able to designate a 501(c)3 nonprofit of his/her choosing to receive a donation from Sofia Sees Hope!

The winner will be announced Friday, June 4 in the Facebook group, on our public social media platforms, and notified by email.

Let’s Chat About … Genetics and Inherited Retinal Disease

You or your loved one just received a clinical diagnosis of Leber conge n ital amaurosis (LCA), a rare inherited retinal disorder caused by a mutated gene. The disease causes severe vision loss at birth and affects the peripheral rod cells that allow night vision and the central cone cells responsible for fine detail and color vision. What now?

The next most important step is to get a genetic test for a confirmed genetic diagnosis to clarify the underlying genetic explanation of the disease. Finding the specific gene causing the defect is critical for moving forward with research and treatment.

Genetic counselors like Emily Place help navigate the complex world of gene mutations, genetic testing, and genetic diagnoses. She is among the more than 4,700 certified genetic counselors nationwide, and she specializes in counseling families living with inherited retinal diseases (IRDs).

Place, a Licensed Genetic Counselor and Research Study Coordinator at Massachusetts Eye and Ear (MEE), discussed her role in the ever-evolving world of genetics in our March webinar episode: “Let’s Chat About…the ins and outs of genetic testing.” Sofia Sees Hope Director of Marketing and Communications Elissa Bass moderated the monthly series, which you can watch here.

Place began her work at MEE’s Ocular Genomics Institute (OGI) in 2011, about the same time the first clinical trials were underway for a vision-improving gene therapy. Six years later, researchers identified, and regulators approved LUXTURNA®, the first gene therapy treatment for an inherited disease, and specifically for LCA2-RPE65, one of the more than 25 gene mutations associated with LCA.

Before OGI, Place worked as a pediatric genetic counselor at Children’s Hospital of Philadelphia, the same place researchers and Spark Therapeutics developed that RPE65 gene therapy.

She earned a Bachelor of Arts in Biology from the University of St. Thomas and her master’s degree in Human Genetics from New York’s Sarah Lawrence College, which in 1969 established the first graduate degree program in genetic counseling. With ever-expanding genetic studies, the profession dramatically increased with more than 50 programs now in the United States.

Basic Genetics

The Human Genome Project (HGP) began in 1990 as an international, collaborative quest to map and understand all the genes of human beings and their roles in health and disease. The project, completed in 2003, revealed there are probably about 20,500 human genes, referred to collectively as our genome, according to the National Human Genome Research Institute.

Scientists have since identified more than 30,000 genes in our body and more genetic causes of inherited conditions, and more research remains to be done to better understand the causes of inherited conditions and to identify more genes.

“Genes are instructions or blueprints that tell us how to grow and function,” Place said.

This genetic information is organized in our chromosomes and can be found in every cell of our body.

More than 200 genes have been identified as playing a specific role to help retina function.

“These inherited retinal conditions can arise because of a genetic variation or change within a gene that we know is important for retinal function and, what we really mean here, is that this genetic change is changing the genetic code in some sort of way that is causing the gene not to function properly within the retinal cells.”

With a few exceptions, she said, a general eye exam will not reveal the underlying genetic explanation for retinal disease.

“That’s where genetic testing is necessary to rule in or identify which one of these 200-plus genes could be the underlying explanation and thus, more definitively rule in an inherited condition and provide a more definitive specific genetic diagnosis.”

The most common pattern for inherited retinal diseases to occur is a recessively inherited condition, the result of inheriting a genetic variation in two copies of the gene, one of those copies inherited from mom and one from dad.

“In these recessive conditions, generally, there may be no family history of anybody else in the family with similar conditions, and that’s because individuals can be carriers, and they may carry one copy of a variation and one copy of their gene, but they have another that can compensate.

“Carriers can be asymptomatic and run through multiple generations and not even know that they’re carriers, and it isn’t until two carriers meet that there’s even a chance for both of them to pass on the genetic change.”

Specific Genetic Identification Versus No Clear Explanation

Counselors help in multiple ways as a family or patient is working toward a genetic diagnosis. Place can begin counseling families before testing, gleaning family history details, reviewing complexities of different inheritance patterns, and looking into what can and cannot be learned from testing.

“It’s also exploring with patients and families whether this is the right time for genetic testing. Is this something that the individual is ready to move forward with or is it something that maybe should be discussed or pursued a later time?”

Counselors can work with families after testing, reviewing the result, whether it be that the testing identified a specific gene or that no clear explanation was found, which happens 30 percent of the time, Place said.

No clear explanation could mean a negative result or an inconclusive result. A negative result can mean no genetic variations were identified. An inconclusive one could be that variants were identified within one to two genes, and the lab does not currently have enough data to classify those variants as disease-causing, but they also cannot be ruled out as not disease causing, she said.

“Sometimes additional testing of other family members may be helpful in resolving the significance of those variants, or that it’s going to take some time and more genetic knowledge is needed to better classify those variants.”

Working with a counselor also helps sort out next steps to take, including the possibility of periodically checking back with your genetic counselor to see if more recent research has updated results or new testing options.

“A True Privilege” To Create Relationships

Long-term relationships can develop between counselors and families after testing. If the test identified a specific gene, they discuss the result, assess the risk of other family members having the mutation, coordinate whether they should get tested, and maintain communications going forward about potential genetic-related treatments and therapies.

Place said it may not be the case with every counselor, but long-term relationships with families are the norm in her work.

“I think every clinic and counselor’s experience will be a bit different. I have the true pleasure of working within an IRD clinic where we’ve had long-term relations with the families, and I get to see families back over the course of their visits with us, and so it is a true privilege to be able to create these longer relationships with families.”

Her approach to testing is that a patient diagnosed with any type of IRD should undergo a full IRD panel testing so as not to miss a particular gene.

She also said it’s important for the patients and families to have back-and-forth relationships with their ophthalmologists.

“It’s definitely a two-way relationship, continuing to stay engaged with your providers, but your provider also thinking about being on top of the different testing options that are available.”

Getting Genetically Tested

A person needs a doctor’s order to be genetically tested. Diagnostic testing is done on a patient’s blood or saliva sample at a clinically certified lab that analyzes a specific set of genes identified to be the cause of retinal condition.

Whether you are living in a rural area or a city, you can find genetic counselors and information about testing through the National Society of Genetic Counselors (NSGC) or local genetic providers through the American College of Medical Genetics and Genomics (ACMG).

ACMG is a place to locate a Medical Geneticist (MD/physician), as well as medical genetics clinics. The search ‘Find a Genetic Service’ can be used to locate a genetic professional.

Search engines in both organizations bring up regional options by entering your zip code. Counselors can meet in-person with patients or, depending on the clinic, via telehealth, by phone, video conferencing, and other virtual methods.

Testing resources also can be found through medical or clinical genetics’ departments in your hospital system.

Also, Sofia Sees Hope has donated more than $140,000 to fund free genetic testing for individuals with inherited retinal disease through the My Retina Tracker® program, launched and managed by the Foundation Fighting Blindness. The program is an open access, no-cost genetic testing program for individuals with a clinical diagnosis of an IRD.

“So much has changed in terms of access to genetic testing for inherited retinal diseases over the last several years, and it’s more available to patients than it ever has been in the past. I would say this is really a good time to work toward getting a genetic diagnosis – getting genetic testing if you haven’t had it or re-engaging with your providers if you’ve had testing years ago without a positive result and discuss updated testing options.

“There are resources out there and available, so there are plenty of individuals like me that are available to help facilitate testing or get you in touch with the right counselor or medical geneticist to help facilitate testing for you.”

‘Give Us Hope’: Bringing Together Leber Congenital Amaurosis Researchers and Patients

Promising gene therapy research – characterized as having a good potential to restore vision – is underway to help visual impairment caused by a form of Leber congenital amaurosis (LCA) attributable to a mutation in the IQCB1 gene.

Amy Laster, PhD, Vice President of Science and Awards Programs for the Foundation Fighting Blindness, shared the research news as part of a recent LCA Research Update webinar summarizing results of an IQCB1/NPHP5-associated retinal disease Scientific Advancement Workshop conducted a week earlier.

Laura Manfre, Sofia Sees Hope Co-Founder and President, said more than 40 leading experts in ophthalmology and gene research gathered for the virtual workshop to share research and patient perspectives and identify the next steps to advance treatment for the patient community. Hope in Focus ( formally Sofia Sees Hope) and the Foundation Fighting Blindness hosted these Scientific Advancement Workshop to widen the circle of research awareness, build a framework or platform for sharing knowledge, foster collaboration among stakeholders, identify gaps, and set priorities for action. The format was based on a similar program run earlier for the RDH12 gene.

“Our objective today is to engage you and our IQCB1/NPHP5 community to seek to advance treatment for ourselves and our loved ones…” Manfre said in her introduction.

“There are no easy answers and there are no quick or fast solutions; just wanted to set that expectation up front even as we are very excited to share the news that we have for you.”

Early-stage translational research

The reported results are from early-stage translational research, which involves moving discoveries from basic science and animal models to applying them in human clinical trials.

The news comes after a successful proof of concept or feasibility study by Dr. Gustavo D. Aguirre, VMD, PhD. He is Professor of Medical Genetics and Ophthalmology at the School of Veterinary Medicine, University of Pennsylvania, and he identifies dogs with inherited eye and retinal degeneration.

Dr. Aguirre will be presenting results of his proof of concept gene therapy study on LCA-NPHP5 dogs in a paper soon to be published in a peer-reviewed journal. The research is detailed in bioRxiv (pronounced bio-archive), a repository for preprinting papers prior to publication.

Laster said the study showed that photoreceptors in treated areas had structural improvements and the dogs had improved visual function.

Researchers sent dogs through an obstacle course under dim light and under bright light. Navigating with their treated eye, the dogs had faster travel times and fewer collisions than when they navigated using their untreated eye.

She called the findings very promising, saying, “We’re excited about these results.”

Laster also cited ongoing clinical studies suggesting that the structure of the central retina or macula is preserved for many years despite having significant loss of vision.

“This, if you will, dissociation between the structure and function suggests that a gene therapy targeted at the central retina not only could work but has a good potential to restore lost vision,” she said. “So we build on this proof of concept and clinical knowledge toward translating these laboratory-based research concepts into clinical trials for patients.”

Next steps

The next steps include designing clinical trials and identifying relevant endpoints and outcomes to measure the safety and effectiveness of the gene therapy.

Webinar speaker Todd Durham, PhD, Vice President of Clinical and Outcomes Research at the Foundation, said the dog model studies began about four years ago. He said it is unknown when clinical trials would begin because more work needs to be done prior to launching them. Durham emphasized the importance of the research results, saying, “They’ve very much ticked off a major milestone in this proof of concept canine model.”

Scientific workshop participants also learned that Dr. Aguirre and his colleague, Dr. William A. Beltran, DVM, PhD, co-founded a Philadelphia-based biotechnology company called LuxFiat Therapeutics.

Laster said this would position the scientists to advance the gene therapy into clinical trials and said that the Foundation will continue to do all that it can to accelerate any clinical development.

The Foundation, the largest private funder of research for treatments and cures of blinding retinal diseases, has raised nearly $800 million since its inception and currently funds more than 80 research projects globally. Dr. Laster oversees the Foundation’s preclinical research portfolio consisting of research awards in funding programs that support career development, laboratory-based science research, translational research, and multi-investigator program projects.

In the question-and-answer session, Durham discussed a query from the audience as to whether it was unusual to receive an incorrect diagnosis of retinitis pigmentosa (RP) before later getting a confirmed genetic diagnosis of Leber congenital amaurosis from Spark Therapeutics.

Durham said it was not unusual and that it was great the audience member got a genetic diagnosis.

“The clinical manifestations of what many ophthalmologists observe when they do an exam can overlap quite a bit from various conditions,” he said. “Ultimately, at the end of the day, the fact that you got a genetic diagnosis is most informative for you, and that’s our hope that there will be more access to genetic testing. Just to reassure you, I don’t think your story is very unusual at all, unfortunately, but hopefully access to genetic testing going forward is going to make that a less frequent story.”

Supporting the Leber congenital amaurosis community

Manfre, responding to a question about help specifically for those with the IQCB1/NPHP5 mutation, said Sofia Sees Hope supports the entire Leber congenital amaurosis community and suggested looking at the website’s Resources page and joining a highly active IQCB1/NPHP5 Facebook group that she joined because her daughter Sofia has the same genetic variant.

Durham also devoted the beginning of the webinar delivering preliminary information from an ongoing patient survey on perspectives of people affected by LCA or RP and their caregivers.

He said the survey results will be available to the community after final analysis of the data.

Here are the topics addressed in the survey developed by Sofia Sees Hope and the Foundation:

Diagnostic Journey
Current Best Corrected Visual Acuity
Visual Symptoms
Other Related Conditions
Worries
Impact on Your Family Overall
Participating in Clinical Trials
Motivations for Participating in a Clinical Trial
Anything Else to Share with Researchers.

Under the last topic, a participant responded: “Time is vision. Please hurry for IQCB1. Give us hope.”

“Let’s Chat About …” Webinar Provides Insight Into How the FDA Handles Rare Disease Treatments

Researchers and regulators did not miss a single step in the fast-tracked federal process of developing successful COVID-19 vaccines. And the same goes for fast-tracking gene therapies for rare disease treatments, Dr. Wiley A. Chambers II of the U.S. Food and Drug Administration said during a recent webinar hosted by Sofia Sees Hope.

As the Supervisory Physician in the FDA’s Division of Ophthalmology, Dr. Chambers discussed vaccines and processes necessary for drugs to be approved for human use in our February 16 webinar episode: “Let’s Chat About…What it takes to receive approval for a new treatment for rare disease.” Sofia Sees Hope Director of Marketing and Communications Elissa Bass moderates the free monthly webinar series. You can watch the webinar here.

Dr. Chambers joined the FDA in 1987 as a primary reviewer for ophthalmic drug products and in 1990 became a Supervisory Medical Officer for Ophthalmologic Drug Products. He has supervisory responsibility for the clinical review of ophthalmologic drug products and ophthalmic therapeutic biologic products submitted to the Center for Drug Evaluation and Research.
He has clinically reviewed more than 100 ophthalmology drugs that have received FDA approval, including the first gene therapy, LUXTURNA®, approved in December 2017. The drug – administered through subretinal injection – is a human-engineered virus containing a healthy version of the RPE65 gene that causes blindness in patients with a form of Leber congenital amaurosis (LCA) called LCA2 (RPE65).

Vaccines: “We’ve Got That Down”

Talking about the recently authorized COVID-19 vaccines, Dr. Chambers said it wasn’t a matter of starting from scratch.
“We know how to make vaccines. We’ve been making vaccines for over a hundred years. We make new vaccines every year. The flu shots that come out are a change in the vaccine every year and we put a vaccine out every year that’s specific to different strains of the flu. Every year. So, we’ve got that down.”

The process did differ in two aspects because of the urgency to quell the pandemic.

“What happened with COVID is the federal government said, ‘You companies go make the vaccines. We’re still going to go through the normal process of testing it, having the FDA go and review it, but don’t wait to see if the product works or not before you make up all those doses. Make them now. And we’re going to pay you for them whether it works or not.’

“So, the companies went and did that. We didn’t skip any steps. We know how to make vaccines. We did what we typically know. We made a series of vaccines and at the same time the companies were mass-producing, as everybody would suggest now, not enough, but made a number of doses out so that when the products got approved, they already had doses made. They didn’t have to start manufacturing doses.”

The second distinction is COVID-19 – which has killed more than 550,000 Americans and more than 2.6 million people worldwide – created a public health emergency requiring urgent mitigation.

Rather than getting FDA approval or clearance, COVID-19 vaccines received Emergency Use Authorization (EUA), one of several tools the FDA is using to help make certain medical products available quickly during the pandemic. Under an EUA, the FDA makes a product available to the public based on the best available evidence, without waiting for all the evidence that would be needed for FDA approval or clearance.

EUAs are effective until the emergency declaration ends, and they also can be revised or revoked by the FDA as it continues evaluating available data and patient needs during the public health emergency.

Developing gene therapies to improve vision also meets fast-tracking requirements because vision loss is considered serious. Fast-tracking gene therapy in ophthalmology means extra meetings and FDA communication.
“But you’re not skipping any steps at all,” Dr. Chambers said.

Improving Visual Acuity

The FDA is a gatekeeper requiring that a product be safe and efficacious for its intended population before it can be marketed for human use. Dr. Chambers regularly talks with patients and solicits comments from groups about what is important to them in the search for potential treatments or cures. The information then can be modified into endpoints, or outcomes, measured scientifically through clinical trials.

“We strive to approve products that are going to benefit patients. That’s who’s going to take them. That’s who they’re for, that’s what we’re trying to go and match.”

Dr. Chambers said his personal preference is cures.

“I like diseases to go away. My endpoint, if given the choice, would be to have something go away. But I’ve got to have a product that’s capable of doing that too, so there’s a reality that sets in that I may not get a product that cures, that does everything I would like it to go and do, but we strive for as many of those things as possible and to then try to include them in the trials.”

As an example, he cited visual acuity (clarity of vision) and the ability to drive.

“For better or worse, in the United States, if you want to be independently mobile, as far as living alone in many parts of the country, you have to be able to drive…and every state in the United States has a visual acuity value that if you’re not at the visual acuity or better, you can’t get a driver’s license…

“We think visual acuity is an important thing to be able to improve for patients. Not because they say they want it but because we know if they don’t achieve that level, they’re not going to be able to drive and they’re not going to have the mobility that we know people want.”

Whether someone can see better in some aspect is an important endpoint, even if it means vision is not completely restored.
“I frequently make the comment that my head is going to hurt just as much if I get hit by a ball that I saw or that I didn’t see. If I have a blind spot and I can now not see a ball coming to me and I get hit with that ball, it’s going to hurt. It would have been nice if I had had the full field of vision so that I could see the ball coming and avoid it. So, if I improve my field of vision, even if it’s not dead center, even if it’s not visual acuity, it’s still a benefit to me.

“You’ll see us potentially approve products on things less than fixing the whole thing, but fixing some portion, and again, we’re absolutely open to suggestions by people of things that they think benefit them that we could use as endpoints.”

Research Models

Mice and rats, cats and dogs, rabbits and monkeys – they all play important roles in developing new treatments and drugs. With inherited retinal disease, dogs take the cake.

Researchers use animal models that most resemble humans, and in the case of LCA, studies showed dogs gained improved vision, leading to the federal approval of the groundbreaking drug LUXTURNA®.

Lancelot, a Briard descended from an ancient breed of large herding dogs in France, carried the same RPE65 gene that caused his blindness.

By contrast, rats would not make for good study models in retinal research because they do not have a macula.
“Rats are more interested in going around in the dark. Their eyes are different,” Dr. Chamber said. “You want to pick an animal that has similar receptors in that species.”

Lancelot and his cousins paved the way for FDA approval of the first-ever gene therapy for inherited disease in humans.

Road to Approval through Clinical Trials

The goal of the FDA is to approve a product proven to be safe and efficacious. The product’s potential adverse events are weighed against its benefits in the balancing act of risk versus reward.

The agency regulates interstate commerce, acting as a gatekeeper for any product intended for human use. Because a biotechnology company probably wants to ship the investigational drug to clinical investigators in many states, it first must seek an exemption from that legal requirement. The exemption is granted after the company submits its research for review.
“If we say nothing, they’re allowed to proceed. If we have an objection, we tell them in 30 days.”

The company can move forward with trials after the FDA assigns an Investigational New Drug (IND) number.

Beware of phony trials, Dr. Chambers said. The website clinicaltrials.gov lists both trials that have been issued an IND number and those overseen by the FDA. It also lists trials not reviewed by the FDA.

“First thing: Ask what the IND number is,” he advised. Dr. Chambers noted that clinical trials, for better or for worse, are never conducted for the people in the trial. They are geared to inform what is going to happen in the future with the product.
Rare diseases – such as the more than 25 forms of LCA and other rare inherited retinal diseases (IRDs) – present bigger challenges in finding participants for clinical trials because the rare disease community inherently represents fewer people. The definition of a rare disease in the United States is one affecting fewer than 200,000 Americans.

If only 30 people are studied, you are likely to see adverse events that occur in 10 percent or more of individuals, he said. If you study 300, adverse events can be picked up at a rate of 1 percent or above.

“It’s all about the numbers, numbers, numbers, numbers…It’s a numbers game.”

The process wends its way through more protocols, comparisons, studies, and trials until a company submits a marketing application reviewed by experts at the agency.

The FDA may hold Advisory Committee meetings for public comment from external reviewers, special government employees, patients, consumers, and advocates. In the case of LUXTURNA®, Sofia Sees Hope Co-Founder and Board Chair Laura Manfre testified at an Advisory Committee meeting on behalf of Spark Therapeutic’s application.

FDA oversight does not end after it approves a drug and a biotechnology company begins marketing it for human use.

“We now start monitoring for adverse events that might occur with the product,” Dr. Chambers said.

The process of receiving federal approval of products for human use can be long and expensive: LUXTURNA® research, development, and approval took 12 years and $500 million. The rewards, though, can be priceless, in helping children and adults see the world in a new light.