After NGM Biopharmaceuticals’ most advanced in-house program failed in a mid-stage study last year, the biotech said it would focus on drug candidates covered by a partnership with Merck, including an antibody in clinical development for a degenerative vision disorder without FDA-cleared treatments. The outlook for this NGM drug looks bleak after data reported on Monday showed it failed a phase 2 study.
NGM tested its drug, NGM261, in geographic atrophy, an advanced form of age-related macular degeneration. These retinal lesions are associated with excessive activity of a part of the immune system called the complement system. This activity damages the macula, causing the patient to lose central vision. Although this vision loss is irreversible, NGM and other biotech companies researching treatments for the disease are developing drugs to slow the deterioration associated with the disease. NGM261 is an antibody designed to block a complement system protein called C3.
The phase 2 study enrolled 320 patients diagnosed with geographic atrophy in one or both eyes. These participants were randomly assigned to receive the experimental NGM therapy injected into the eye every four weeks or every eight weeks, or a sham injection given at the same intervals. Geographic atrophy leads to the formation of lesions on the retina. The primary objective of the clinical trial was to measure the rate of change in lesion area after 52 weeks of treatment. In results announced Monday, NGM reported a 6.3% reduction in the number of people receiving treatment every four weeks and a 6.5% reduction in the number of people treated every eight weeks. However, these reductions were not statistically significant compared to the changes seen in those who received the dummy treatment.
Despite missing the primary endpoint of the trial, NGM pointed out that fewer patients in the treatment group developed choroidal neovascularization, the growth of new blood vessels that leads to loss of vision. In addition, NGM performs additional analysis of trial data that adjusts for what the company says is high variability in lesions. In an investor presentation, the company said excluding the quartile of patients with the largest lesions at baseline from the study shows greater reductions in lesion area over 52 weeks. The company described these results as “potentially encouraging findings warranting further evaluation.” However, the FDA generally frowns on post-hoc testing that seeks to find a positive result from a failed study. In such cases, the regulator usually requests another clinical trial.
NGM could be hoping for a similar outcome to what happened with Apellis Pharmaceuticals, a company that recovered from a stumble in a clinical trial. Just over a year ago, Waltham, Mass.-based Apellis reported that one of the phase 3 studies testing its drug had successfully met its primary endpoint at 12 months, while the another had failed. The company continued both studies and earlier this year reported 18-month data that showed a reduction in lesions. Apellis executives attributed the failure of the earlier clinical trial to some patients with a rapidly progressive form of geographic atrophy. In these patients, it takes longer for the drug to show an effect, which was evident at 18 months. In July, the FDA accepted the biotech’s drug application, including 18-month data. The agency has set a target date of Nov. 26 for a regulatory decision.
Charles Wykoff, research director at Retina Consultants of Texas and investigator on the NGM621 study, said in a prepared statement that there can be wide variability in results between complement inhibitor tests for geographic atrophy and as scientists are still learning how this variability affects the evaluation of experimental therapies for the disease. He added that the finding of choroidal neovascularization combined with signals from additional scans suggest that the drug NGM may play a role in the treatment of geographic atrophy. NGM said additional findings will be presented at the Retina Society’s annual meeting in November.
NGM began its alliance with Merck in 2015. The pharmaceutical giant paid NGM $94 million upfront and took a stake in its partner valued at around $106 million. Under the terms of the deal, Merck has the option to out-license NGM621 after Phase 2 testing is completed. Investors are not betting on that outcome in light of the clinical trial failure. NGM shares fell more than 70% on Monday.
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