Let’s Chat About … the Importance of the Patient Voice in Rare Disease

We hear a lot these days about the necessity of the patient voice in developing treatments, especially for people living with rare disease, such as Leber congenital amaurosis (LCA) or other rare inherited retinal diseases (IRDs).

So, how does the voice of the patient manifest in helping speed up the process of drug development and bringing treatments to market?

In several specific ways, according to Jill Dolgin, PharmD, Head of Patient Advocacy at a clinical-stage biotechnology company. Here they are:

• Get a confirmed genetic diagnosis through genetic testing to determine the underlying cause of the disease.
• Add your voice to science by joining a patient registry that gives researchers necessary information for clinical trials.
• Take part in Natural History studies that glean knowledge and an independent understanding of diseases over time.

People also should tell their stories and bring awareness to as many people as possible to help advance research.

Dr. Dolgin leads Patient and Professional Engagement Strategy at Applied Genetic Technologies Corporation (AGTC), headquartered in Alachua, Fla., with offices in Cambridge, Mass. The company develops transformational genetic therapies for IRDs, and Dr. Dolgin works to drive disease and clinical trial awareness efforts for the AGTC pipeline.

Sofia Sees Hope featured her in its September webinar episode: “Let’s Chat About…the importance of the patient voice.” Director of Marketing and Communications Elissa Bass moderated the monthly series.

Dr. Dolgin has more than 20 years of global pharmaceutical experience in Medical Affairs, Corporate Communications, Patient and Professional Advocacy, and Public Policy. She earned a doctorate in clinical pharmacy from the University of the Sciences in Philadelphia and a Bachelor of Science in pharmacy from The Ohio State University.

At AGTC, she ensures that patient needs are considered and incorporated into every aspect of drug development. Externally, she collaborates with patient advocacy groups, such as Sofia Sees Hope, to educate patients and families about the importance of taking part in clinical trials, gene therapy, and the value of listening to the voices of patients and their families to help the media, healthcare professionals, payors, and policymakers understand the challenges encountered by patients as they live with rare retinal conditions. 

Dr. Dolgin brings patient voices to the corporate table, noting AGTC’s mantra: “No decision about the patient without the patient.”

Genetic Tests, Patient Registries & Natural History Studies

Once a patient receives a clinical diagnosis of LCA, a genetic diagnosis via genetic testing is the next critical step toward advancing research. AGTC and Sofia Sees Hope provide funding to the Foundation Fighting Blindness (FFB) to help patients gain free access to genetic testing. 

More than 100 mutations could cause various forms of eye disease; a confirmed genetic diagnosis narrows the condition to one or more gene mutations. The next steps include finding whether a treatment exists for the condition, whether technology exists to correct the mutation, and/or whether clinical trials are underway for that condition.

That’s when joining My Retina Tracker® registry, a free and secure online registry launched by FFB, comes into play. Dr. Dolgin talked about the necessity of this bank of patient medical information that gives voice to the patient and a role in contributing to science by driving research for LCA and IRD treatment and cures.

With rare disease, where the history and progression of the disease over time is particularly poorly understood and unknown, Natural History studies should be conducted before beginning a clinical trial. 

Researchers gather specific information from patients to better understand a disease’s progression, using the data to assess whether an investigational treatment administered during a trial is affecting that progression. 

Incorporating the patient voice into the development plan goes beyond the clinical trial, she said. Patient and caregiver feedback should be considered throughout the development and commercialization of a product. For example, when developing the formulation of a product given by mouth, researchers need to keep in mind the specific needs of patients, whether they be children, elderly, or anyone with difficulty swallowing, and consider developing a liquid product.

They also should consider ease of use in product packaging. Just trying to open the medicine bottle can be daunting for someone with arthritis. She jokingly said safety caps should be labeled adult-proof, rather than child-proof, because they’re so often difficult to open. 

Becoming Part of a Clinical Trial

Dr. Dolgin’s job also includes discussing clinical trials as a treatment option and finding appropriate participants for clinical trials, a challenging task for developing treatments and cures for rare diseases with smaller pools of potential participants. A rare disease is one that affects fewer than 200,000 people. 

Patients considering taking part in a clinical trial need to understand the process of clinical development, the goals, and the expected outcomes for each stage of development, from pre-clinical animal studies to human studies, she said.

Researchers divide human studies into three phases. In rare disease studies, they combine Phase 1 and Phase 2 studies because of the small number of patients. They design these early-phase trials primarily to assess safety over a wide dosage range and to assess potential biologic activity or efficacy in a small number of patients. 

The final phase before Food and Drug Administration approval is Phase 3, in which researchers enroll a larger number of patients and administer the highest and safest dose given in the Phase 1/2 trial. The goals are to further assess any safety issues and evaluate the potential efficacy of a product in a larger number of participants. In rare disease trials, often fewer than 100 patients take part in each trial phase.

Even when a lot of people initially make up a pool of potential participants, those big numbers shrink fast when people understand the burden of time required to take part in the trial, including multiple scheduled visits in the first year of the trial. 

Most IRD trials last 5 years to determine long-term efficacy and safety. The time commitment can impact childcare, time away from school, work, and family commitments. Time and expense for another person to accompany a clinical trial patient with vision loss is another variable. The trial’s sponsor generally covers travel and lodging costs, but patients should confirm whether that is the case before agreeing to participate.

A potential participant with a clinical and genetic diagnosis may not meet all the inclusion criteria because of the severity of their disease (either too good or too severe), or because they may have other medical conditions that might interfere with medications provided during the trial or the medication under investigation. 

While more than a thousand gene therapy developers are out there, with 50 dealing with ophthalmologic drug development, Dr. Dolgin said, the road to a marketed drug is long and arduous, often taking 10 to 15 years from laboratory and animal studies to final approval for use in humans.

About a hundred trials for various eye diseases are in preclinical stages, with about 60 ongoing clinical trials. It’s a big trial-and-error process, she said, citing trial failure rates of 80 to 90 percent.

She described the two kinds of gene therapies on the market and in development, the first being gene addition, in which doctors insert a functional copy of the gene, and the second, gene editing, by removing the mutating gene and inserting the correct one.

Current AGTC Research Highlights

Along with AGTC’s patient advocacy work, Dr. Dolgin said the company has made exciting progress with three advanced clinical trials: 

The first deals with X-linked Retinitis Pigmentosa (XLRP). Retinitis Pigmentosa (RP) describes a group of rare genetic eye diseases that damage light-sensitive cells in the retina, leading to loss of sight over time. Of the 200,000 RP patients, about 10 percent have X-linked RP, in which a mother passes down the non-working gene to her male children.

AGTC just completed Phase 1/2 of the XLRP clinical trial and is currently  enrolling in a Phase 2 expansion trial and screening for participants for its Phase 3 trial to be initiated soon. 

Achromatopsia (ACHM), an inherited condition caused by mutations in one of several genes, is the subject of two separate Phase 1/2 clinical trials for individuals with a mutation in either the CNGA3 or CNGB3 genes. ACHM is associated with extremely poor visual acuity, extreme light sensitivity, and complete loss of color discrimination. 

AGTC completed Phase 1/2 clinical trial enrollment for both the CNGA3 and CNGB3 trials.