- A long-shot bid from Lexicon Pharmaceuticals to reverse a March rejection of its diabetes drug Zynquista was denied by the Food and Drug Administration, sending shares in the Texas-based biotech down by as much as 15% Monday.
- Apparently undeterred, Lexicon said it would escalate its appeal to the FDA's Center for Drug Evaluation and Research, a higher division than the one that originally received the drugmaker's initial request.
- In March, the FDA knocked back Lexicon's application for approval of Zynquista in Type 1 diabetes. Mixed late-stage trial results in Type 2 announced four months later led Lexicon's big pharma partner Sanofi to exit its development partnership on Zynquista, leaving the biotech to advance the drug on its own.
While Lexicon isn't giving up on Zynquista (sotagliflozin), the drug's chances of getting approved in the U.S. appear slimmer after the FDA reiterated its initial rejection decision in Type 1 diabetes.
The biotech filed a formal dispute resolution request with the FDA in September, the same month it reached a settlement with Sanofi over the pharma's decision to end the companies' research collaboration. That settlement, which had Sanofi pay Lexicon $260 million, returned to Lexicon all rights to Zynquista, a type of diabetes drug that blocks two proteins involved in glucose regulation.
While Lexicon's CEO had previously described conversations with FDA on the company's appeal as constructive, those discussions did not sway the agency's Office of New Drugs, the division that received Lexicon's request.
Lexicon will appeal OND's decision to CDER, the next level in the FDA's departmental hierarchy. Investors, though, don't seem optimistic that effort will result in a different outcome, selling off Lexicon shares Monday.
While Lexicon's efforts to reverse the FDA's rejection are unusual, they're not without precedent. In 2016 and 2017, PTC Therapeutics attempted to secure U.S. approval for its Duchenne muscular dystrophy drug Translarna (ataluren), only to see its application first refused and then later denied by the agency. An appeal via the OND's dispute resolution mechanism led to a Feb. 2018 denial that included a request for new data.
Lexicon is taking its dispute one step further by appealing to CDER, however.
"We don't have any available historical data to gauge the success rate of CDER appeals following an initial OND denial (this is a very uncommon event) — but we're inclined to believe any data that does exist likely won't support much in the way of optimism here," wrote Stifel analyst Stephen Willey in a Dec. 2 note to investors.
Company executives expect to have a decision from the FDA by February 2020, according to Willey.
Lexicon may have another opportunity for Zynquista in Type 2 diabetes. Data from the first three Phase 3 trials of the drug in the later-onset form of the condition were mixed, but results from six other studies are still forthcoming. Pending those, Lexicon hopes to file for approval in the U.S. and in Europe, where Zynquista is already approved for people with Type 1.
It's that effort that Lexicon hopes will attract another pharmaceutical company partner.
"Regaining worldwide rights allows us to advance our efforts to realize the full value of the Zynquista program as we prepare for regulatory filings in the U.S. and in Europe in type 2 diabetes," said Lexicon CEO Lonnel Coats in a Sept. 10 statement. "We believe that this potential, along with a European approval in type 1 diabetes, offer an attractive opportunity for potential collaborators."