The revelation of a patient death in Bristol Myers Squibb’s phase 3 trial of a potential pulmonary fibrosis treatment has raised concerns ahead of the study’s readout, but analysts were quick to dispel worries about broader implications for the drug mechanism involved.
A May protocol amendment for European sites in the Aloft program describes multiple cases of liver toxicity, including a patient who died after “multi-organ failure involving acute hepatic injury.”
“Most events were mild, transient, associated with other medical conditions, and occurred in patients receiving concomitant medications known to cause elevations of liver enzymes,” a BMS spokesperson told Fierce. “Most events resolved with no change to study treatment.”
The drugmaker is unsure whether the patient who died received the treatment, an LPA1 inhibitor called admilparant, or placebo, as unblinding has yet to occur.
Despite the safety concerns, an independent data monitoring committee has recommended the program proceed, the spokesperson added, with BMS expecting topline data in idiopathic pulmonary fibrosis by the end of 2026 and in progressive pulmonary fibrosis early next year.
“We are pleased with the progress of the phase 3 Aloft program,” the spokesperson said.
Lysophosphatidic acid receptor 1 is involved in the healing of wounds and the creation of fibrotic scar tissue that is characteristic of pulmonary fibrosis. Admilparant is potentially first-in-class, as other attempts to drug LPA1—including from BMS and other pharmas like Amgen—have been unsuccessful.
Analysts largely dismissed concerns that the death spells trouble for the LPA1 mechanism writ large.
“We continue to believe there is minimal on-mechanism risk here and that this potential signal is molecule- and dose-specific, if anything,” William Blair analysts wrote in a note to investors yesterday. “Experts we have discussed the LPAR1 mechanism with remain optimistic about this new class.”
Analysts from Leerink agreed, though they acknowledged that the death “raises questions.”
“The details are murky and do not yet confirm a class-wide or even drug-related signal,” the Leerink analysts wrote yesterday. “The single fatality had multiple comorbidities, and the hepatic failure did not demonstrate a classic drug-induced liver injury pattern.”
The analysts were writing to assuage investor concerns around an LPA1 drug in the works at Contineum Therapeutics, known as PIPE-791. In addition to the caveats above, analysts also noted that Contineum’s candidate has a “different chemical scaffold” and lower dosage than admilparant.