Arena's lead drug misses on PhII in AD, thwacking stock, but company soldiers on into Phase III
Amit Munshi’s tenure at Arena Pharmaceuticals has almost exclusively been one of success: Taking the reins of a company in the Nasdaq gutter, he’s steered it through multiple positive readouts and even bagged an $800 million upfront deal on a non-lead drug.
On Monday, though, the company announced a failure: Its lead drug, the S1P inhibitor etrasimod, missed the primary endpoint on a Phase II trial for atopic dermatitis, failing to reduce symptoms on a standard clinical scale better than placebo. Yet they will continue on with a Phase III, betting that aberrations at one trial site thwarted that endpoint and that they can repeat success on a metric the FDA uses to evaluate approval.
“We believe we have a molecule that is headed towards being a safe and effective oral opportunity,” Munshi told Endpoints News. “We think that’s going to be a potential game changer for this space.”
Investors, at least initially, weren’t buying it. Arena’s stock $ARNA fell from $87 to $70 post-market in the minutes after the announcement.
It’s not uncommon for companies to launch Phase IIIs after Phase II went bust, although the results are not always pretty. In the past few months, such turnaround attempts from Genfit and Aurinia each failed.
Munshi, though, says he has a case. The drug, he noted, hit on 4 different secondary endpoints, including the one FDA asks for to obtain approval: a clinical score called validated investigator global assessment.
They only failed on the primary endpoints — reduction on the eczema area and severity index, or EASI — because of a “slight anomaly,” CMO Chris Cabell argued.
Nine patients on the drug arm, most of whom were at a single trial site, were taken off the drug after their white blood cell counts fell.
Cabell said the company pointed out that reduced white blood cell counts were part of the drug’s mechanism of action and how it reduced symptoms of autoimmune diseases. The patients were put back on and responded to the drug again, he said, but never reached the level of response seen in other participants.
If you remove those patients from the calculus, the trial would hit the primary endpoint, Munshi said.
“The drug was doing exactly what it was supposed to be doing,” Munshi told Endpoints. “There were a handful of sites — particularly one site — that overreacted.”
Munshi said they got the data over the weekend and reached out to a half-dozen experts, who encouraged them to run the Phase III trials.
They’ll now have a chance to prove if it was just those 9 patients. The goal is to bring forward a drug that has the efficacy of Sanofi and Regeneron blockbuster Dupixent but in a more accessible oral form and without the safety concerns of JAK inhibitors. They’ve already brought the drug into Phase III for ulcerative colitis after a successful Phase II.