Convinced that their third Phase III trial assessing Fovista® (pegpleranib) in wet age-related macular degeneration (AMD) may be as unsuccessful as two earlier pivotal studies of the candidate, Ophthotech disclosed today that it has joined Novartis in revising the terms of the 2014 agreement through which they are co-developing the drug.
In a regulatory filing, Ophthotech cited two failed Phase III trials, OPH1002 and OPH1003, both designed to evaluate the safety and efficacy of 1.5 mg of Fovista in combination with Lucentis® compared to the Roche (Genentech)/Novartis-marketed drug vascular endothelial growth factor (VEGF) therapy alone. The trials enrolled a combined 1248 patients with wet AMD.
Following the trial failures, Ophthotech said it would slash its workforce by approximately 80%. The company had 156 full-time employees as of January 31, and expects to eliminate the jobs of 125 employees this year, Ophthotech stated in its Form 10-K annual report for 2016, filed February 28.
“The failure of two previously completed Phase III clinical trials conducted by Ophthotech, OPH1002 and OPH1003, to show any clinically meaningful visual benefit in adding 1.5 mg of Fovista to a monthly regimen of 0.5 mg of the anti-VEGF therapy Lucentis® (ranibizumab) and the recent failure of a competitor’s Phase II trial investigating the combination of a PDGF [platelet-derived growth factor] inhibitor and a VEGF inhibitor, may be indicative of a low likelihood of success for OPH1004,” Ophthotech disclosed today in a regulatory filing.
The competitor was Regeneron Pharmaceuticals. In September, Regeneron acknowledged that a combination therapy of its marketed wet AMD treatment Eylea® (aflibercept) and the company’s rinucumab, an anti-platelet-derived growth factor receptor beta (anti-PDGFR-beta) antibody candidate, failed the Phase II CAPELLA trial. The combination missed the trial’s primary endpoint of improvement in best-corrected visual acuity (BCVA) compared to intravitreal aflibercept injection monotherapy at 12 weeks.
In May 2014, Novartis acquired from Ophthotech exclusive rights to market Fovista outside the U.S., while retaining U.S. marketing rights, under a licensing and commercialization agreement designed to generate more than $1 billion for Ophthotech.
Holding Off Pending Data
In its filing today, Ophthotech said it agreed with Novartis to revise the agreement. Under the revised accord, the companies agreed to hold off on development, manufacture, and commercialization of Fovista products pending receipt of OPH1004 data and the determination of a regulatory strategy.
The revised agreement also cuts the time Novartis has to notify Ophthotech that it is ending the agreement, though the filing did not give details—and spells out a process for determining the scope and funding for additional clinical trial(s), if any, toward regulatory approval of Fovista.
If the companies cannot come to terms on funding for any additional clinical trial(s), Ophthotech and Novartis will each have to fund half of the cost and expense of such clinical trial(s), Ophthotech said.
Ophthotech permanently waived its right to terminate the agreement if the companies are barred from “materially” progressing the development or commercialization of Fovista products for a specified period due to government actions. Ophthotech said it had previously been liable to pay Novartis a “substantial” termination fee.
The revised agreement also gives Novartis a fully paid-up, royalty-free license to use data from the Lucentis monotherapy arms of Ophthotech’s Phase IIb OPH1001 trial and Phase III OPH1002 and OPH1003 trials outside the U.S. in connection with the development, manufacturing, and commercialization of Novartis-controlled anti-VEGF products.
That license shall continue until the fifth anniversary of the companies’ agreement, or the date the agreement expires or ends, whichever is later, Ophthotech added.