Dive Brief:
- Bristol Myers Squibb has changed a late-stage study of its experimental pulmonary fibrosis drug admilparant to more closely monitor for liver-related side effects, following a “limited number” of instances of liver damage as well as the death of a participant from liver injury, a spokesperson said Wednesday.
- The change to the long-term safety extension to its Phase 3 “Aloft” trial raised investor worries about admilparant’s drug class, called LPA1R inhibitors, which are viewed as a new way to slow progression of the lung disease idiopathic pulmonary fibrosis. Shares in Bristol Myers as well as Contineum Therapeutics, the developer of a similar drug, fell sharply in late-day trading Tuesday before rebounding early Wednesday.
- A spokesperson confirmed that it’s unclear whether the patient who died received admilparant. Wall Street analysts also called the brief share pullback “overdone,” pointing to multiple factors that could’ve contributed to the death and the relatively mild nature of the other side effects observed. Bristol Myers expects to report study results by the end of the year, an announcement that could shed more light on the safety of admilparant and other drugs in its class.
Dive Insight:
LPA1R inhibitors have already had a difficult time in clinical research. Bristol Myers Squibb canceled work on an earlier drug because of liver toxicity. Amgen shelved another it had inherited in a buyout of Horizon Therapeutics.
Bristol Myers submitted the amendment to its trial practices for European Union sites in May. In it, the company called for liver injury to be a “newly classified important potential risk.” Bristol Myers also required closer monitoring of enrollees with abnormally high levels of liver enzymes to check whether they should stop treatment for safety reasons.
Most of the events reported were “mild, transient, or demonstrated patterns consistent with hepatic adaptation” to the drug therapy, according to the amendment. The one fatality resulted from “multi-organ failure,” with liver damage, immune damage to red blood cells and widespread clotting. The enrollee had underlying lung disorders and other complications.
The Bristol Myers spokesperson also reiterated that outside trial monitors have regularly reviewed unblinded safety data and, each time, have recommended that the study continue as planned.
Even with those caveats, the news is “likely to reaffirm historical concerns around liver toxicity” for LPA1R class, even though there are “too many variables to conclude” whether there’s a “true safety signal,” RBC Capital Markets analyst Brian Abrahams, who covers Contineum, wrote in a client note.
“It may not be a drug-related issue, let alone an LPA1-class issue,” added Leerink Partners analyst Roanna Ruiz in a separate note.
Stifel analyst Paul Matteis, who also covers Contineum, noted how the biotech’s drug is designed differently. Contineum is also testing a dose as low as 10 milligrams per day, which could reduce the chances of liver damage.
Admilparant’s Phase 3 trial is one of several coming study readouts that could change the narrative surrounding Bristol Myers, which is facing the patent expiration for its top seller Eliquis and steep revenue declines for many of its older drugs.
