Moving emerging therapies through clinical trials and across the finish line is often challenging—and in some cases, harrowing. Many treatments never make it.
In early 2022, the future looked bleak for ProQR Therapeutics’ two RNA therapies in clinical trials. The biotech company reported that sepofarsen, its RNA therapy for LCA10 (IVS26 mutation in CEP290), did not meet its primary endpoint of improvement of at least three lines in best-corrected visual acuity or BCVA. (Improvement in BCVA was only on average two lines in the Phase 2/3 trial.) That news came despite vision improvements, some significant, for many patients. The endpoint misled ProQR to stop development of its ophthalmology assets—sepofarsen and ultevursen (exon 13 mutations in USH2A)—and attempt to find a company to acquire them.
Mike Schwartz, who was then vice president, global project leader, at ProQR, said, “That was devastating for me, the doctors, and the patients.” He noted that one patient with LCA10 in the trial with only light perception gained enough vision after receiving sepofarsen to see letters on an eye chart. Another LCA10 patient in the study returned to his work as a carpenter after treatment.
Fortunately, a year and a half later, the large European eye care company Théa acquired sepofarsen and ultevursen and formed the Sepul Bio business unit to move the therapies back into clinical trials. Many former ProQR staff went to Sepul Bio, including Mr. Schwartz, who is now their chief operating officer.
The global HYPERION Phase 3 clinical trial for sepofarsen and the LUNA Phase 2 trial for ultevursen are now underway. Using what was learned from the ProQR trials, the Sepul Bio team made significant changes to the designs (protocols) for the clinical trials, changes they believe will greatly improve chances for success. Mr. Schwartz thanked the Hope in Focus team for providing input from patients for the sepofarsen clinical development program.
One major change in the new sepofarsen clinical trial protocol has to do with the placebo. In most clinical trials with regulatory authorization, the treatment group is compared to a placebo or control group to ensure that efficacy is indeed a result of the treatment. In the original sepofarsen trial, treated eyes of LCA10 patients were compared to the eyes of untreated LCA10 patients (i.e., the control group). Comparing treated patients to untreated patients was less than ideal because of significant variations in vision loss among LCA10 patients. So, in the new trial, each LCA10 patient will have one eye injected with sepofarsen and the other will get a saline placebo injection. The patient won’t know which eye is getting the treatment. Sepul Bio believes comparing untreated and treated eyes for the same patient will lead to less variation and a stronger efficacy signal.
Keep in mind that sepofarsen injections are made into the vitreous, the soft gel in the middle of the eye. These intravitreal injections are performed routinely (e.g., monthly) and safely in doctors’ offices for treating age-related macular degeneration. In the sepofarsen clinical trial, patients will receive injections every six months.
Sepul Bio’s RNA therapies, known as antisense oligonucleotides (ASOs), are tiny pieces of genetic material that fix mutations in RNA—the genetic messages that cells read to make proteins critical to the cells’ health and function.
Stay tuned. We will report on updates from the trials as soon as we receive them.
For more information on the sepofarsen or ultevursen trials, send an email to: contact@sepulbio.com.