- Allergan on Thursday touted data from two late-stage trials that showed a drug it in-licensed from a Swiss biotech proved non-inferior to Lucentis in the treatment of an eye disease known as wet-AMD.
- The SEQUOIA and CEDAR trials assessed vision loss, specifically how many letters on an eye chart patients could no longer read after a year of treatment. Patients were either given Allergan's drug, abicipar, at eight-week or 12-week intervals, or Roche 's drug given every four weeks.
- SEQUOIA found vision loss of 15 letters or fewer in 94.8%, 91.3% and 96%, respectively, for the three groups, while CEDAR found similar proportions at 91.7%, 91.2% and 95.5%. Adverse events were similar across the various treatment types, though there were more cases of intraocular inflammation in the abicipar arms. Allergan plans to file a Biologics Licensing Application (BLA) for its drug in the first half of 2019.
While the new Phase 3 readouts indicate abicipar's efficacy is about on-par with Lucentis (ranibizumab), that's not the drug that should concern Allergan. Regeneron's Eylea (aflibercept), rather, has become the dominant force across multiple eye disease indications, including wet-AMD and diabetic macular edema.
Pharma heavyweights like Roche and Novartis are trying to unseat Eylea with their own offerings, but the drug's impressive efficacy profile and relatively clean label have been difficult to outshine. What's more, Regeneron has moved quickly to block traditional competitor in-roads, such as less frequent dosing. U.S. regulators are currently reviewing a 12-week dosing schedule for Eylea, with a target action date of Aug. 11.
Key patents for Lucentis and Eylea don't run out for the next two to five years, meaning Allergan will need to differentiate in order to compete near-term.
One area it hopes to do that is in fewer cases of adverse events. On a July 19 investor call, company leadership noted that while there were higher incidence of intraocular inflammation in the Phase 3 abicipar arms, that could diminish over time as the manufacturing process becomes more polished. And an ongoing, open-label study called MAPLE should help iron out those details.
Within animal studies, Allergan "can look at the effect of the different formulations on the release of inflammatory mediators from white blood cells, and we can show that as we change the formulation, we have a dramatic reduction in the release of inflammatory mediators from white blood cells," said Chief R&D Officer David Nicholson.
Despite the reassurances, analysts on the call probed for more information about commercial prospects and how prescribers would view this new treatment compared to already marketed anti-vascular endothelial growth factor (anti-VEGF) agents.
"Anti-VEGF agents certainly have inflammation as a side effect. The rates vary, even after production, after being in process," Raj Maturi, an investigator in the CEDAR trial and associate professor of ophthalmology at the Indiana University School of Medicine. "For example Eylea most recently had a spate of increases in inflammation, which they weren't sure where it was exactly traced to possibly one batch and then it improved again. This happens on and off."
Maturi added that, in CEDAR, he observed "some inflammation, but it was reversible, it was easily treatable. The number itself at this point in development does not bother me in any way."
Allergan stock was down less than 1% to $174.95 per share at market's open Thursday, but fell further in morning trading — hitting a low of $171 per share.