pSivida announced positive topline results from its first phase 3 clinical trial evaluating the safety and efficacy of Medidur for the treatment of chronic noninfectious uveitis affecting the posterior of the eye (posterior uveitis), according to a company news release. The 129 patient, multicenter, randomized and double-blinded trial was highly statistically significant in meeting its primary efficacy endpoint of prevention of recurrence of disease at 6 months (P < 0.00000001; intent to treat analysis). Safety results were positive. Only 10.9% more Medidur-treated eyes than control eyes experienced an increase in IOP above 21 mmHg through 6 months, which was reduced to 6.1% through the most recent follow-up visits (some as long as 24 months). In the Medidur trial, 87 eyes were treated with Medidur, and 42 eyes were randomized to control and received a sham injection.
At six-months of follow-up:
- 18.4% of Medidur-treated eyes compared to 78.6% of control eyes had experienced recurrence of posterior uveitis (a statistically significant P < 0.00000001).
- 23.0% of Medidur-treated eyes compared to 4.9% of control eyes showed improvement in visual acuity gaining 15 or more letters from baseline on the Early Treatment Diabetic Retinopathy Study (ETDRS) Eye Chart (a statistically significant P = 0.011).
- 31.0% of control eyes compared to 4.6% of Medidur-treated eyes had lost 15 or more letters from baseline on the ETDRS eye chart for at least one observation (a statistically significant P < 0.0001).
- Of the 65 patients receiving systemic therapy (steroids, immuno-suppressants and biologics) at baseline, 52.4% of control patients compared to 18.2% of Medidur-treated patients were still being administered systemic treatment (a statistically significant P < 0.01).
- 27.6% of Medidur-treated eyes compared to 16.7% of control eyes had experienced an increase in IOP above 21 mmHg for at least one observation.
- Of the 64 study eyes with a natural lens at baseline, 9.5% of Medidur-treated eyes compared to 4.8% of control eyes had required cataract surgery.
“The results of this phase 3 trial are extraordinary. With a single injection, Medidur showed the ability to control the recurrence of posterior uveitis, improve visual acuity and prevent vision loss," Glenn Jaffe, MD, Duke University Robert Machemer Professor of Ophthalmology and Chief of the Division of Retinal Ophthalmology and principal investigator for this trial, said in the news release. “The high level of statistical significance achieved in this trial is dramatic and, along with the compelling benefit-risk ratio, suggests an important treatment option for patients who are typically treated with repeated systemic steroids, immuno-suppressants or biologics, often facing recurring attacks of the disease as well as systemic side effects.”
The IOP elevation results for Medidur compare favorably to the phase 3 trial results for Iluvien for diabetic macular edema, which comprises the same micro-insert as Medidur. Other safety results were also positive. Through 6 months, 2.3% of Medidur-treated eyes and no control eyes required an incisional procedure to reduce IOP. Through the most recent follow-up, 3.4% of Medidur-treated eyes compared to 2.4% of control eyes required an incisional procedure to reduce IOP.
“The results from this phase 3 trial indicate that Medidur has the opportunity to be an effective, safe and convenient treatment for this blinding eye disease, avoiding the potentially serious side effects and administration compliance challenges of the cycles of systemic steroids, immuno-suppressants and biologics now used to treat the disease,” Dr. Charles Foster, Clinical Professor of Ophthalmology at Harvard Medical School and Founder and President of the Massachusetts Eye Research and Surgery Institution, said in the news release. “The ability to administer a 3-year course of Medidur therapy for posterior uveitis in a single, in-office injection could allow many patients to significantly improve treatment outcomes and vision, reduce side effects and drastically simplify patient compliance as compared to current treatment alternatives.”
The primary endpoint of pSivida’s phase 3 trial was prevention of recurrence of disease at 6 months. All other efficacy and safety data analyses were exploratory. Topline results and exploratory analyses were all based on intent to treat population.
About Medidur Phase 3 Trials
pSivida is conducting two phase 3 trials to assess the safety and efficacy of Medidur for the treatment of posterior uveitis. These are randomized, sham injection-controlled, double-masked trials. The primary endpoint of both trials is prevention of recurrence of posterior uveitis at 6 months, with patients in both trials followed for 3 years. The first phase 3 Medidur trial, which enrolled 129 patients in 16 centers in the US and 17 centers outside the US, achieved its primary efficacy endpoint with high statistical significance (P < 0.00000001; intent to treat analysis). The second trial, which is still enrolling patients, will enroll up to 150 patients in approximately 15 centers in India. Assuming favorable results from the second phase 3 trial, an NDA is anticipated in the first half of 2017. pSivida plans to seek FDA approval of Medidur based on 6-month data from the two phase 3 trials and a short-duration utilization study of pSivida’s redesigned proprietary inserter, together with data referenced from the phase 3 trials of Iluvien for DME.