Dive Brief:
- Bristol Myers Squibb said Monday that its experimental lung disease drug admilparant succeeded in a Phase 3 trial in idiopathic pulmonary fibrosis, significantly slowing the decline of study participants’ breathing capacity when compared to a placebo over the course of a year.
- However, trial investigators only found a clear benefit among those who received a 60 milligram dose of admilparant. A 120 milligram dose was associated with an impact on disease progression, but the difference didn’t meet the threshold for statistical significance, the company said.
- The failure of the high-dose arm is “confounding and requires further explanation,” RBC Capital Markets analyst Trung Huynh wrote in a client note. Bristol Myers previously made certain trial revisions that sparked liver-related safety concerns about admilparant, too, although the company said Monday that the drug “demonstrated a well-tolerated safety profile” and treatment-related study discontinuations were similar between study groups.
Dive Insight:
Admilparant is the furthest along among a class of idiopathic pulmonary fibrosis, or “IPF,” drugs called LPA1 receptor antagonists. These treatments work by blocking a signaling molecule that plays an important role in lung scarring. They could emerge as alternatives to marketed drugs like Esbriet, Ofev and Jascayd, each of which has limitations.
“These admilparant results represent an important advancement as there remains a need for therapies that are both effective and tolerable for patients living with IPF,” Fernando Martinez, the trial steering committee chair and a medical professor at the University of Massachusetts, in a statement from Bristol Myers.
Earlier LPA1 drugs struggled in clinical testing. Bristol Myers scrapped one because of liver toxicity and Amgen canceled work on another after it fell short in a Phase 2 trial. News last month that Bristol Myers changed safety monitoring protocols in Europe for admilparant’s trial fueled additional consternation among Wall Street analysts and investors and heightened anticipation for the coming study readout.
The announcement Monday that a 60 mg dose helped meaningfully improve “forced vital capacity,” or the amount of air people can exhale from their lungs at once, when compared to a placebo would ordinarily be taken as positive. However, physicians and drug reviewers frequently look to see whether higher doses perform better than lower ones. The lack of this kind of “dose response” sparked debate about admilparant’s prospects.
The results “could be sufficient to support admilparant regulatory approval, but the lack of dose response raises questions about [admilparant’s] profile,” Leerink Partners analyst David Risinger wrote in a Monday client note. “We await detailed results to better understand the drug’s efficacy.”
Others were more positive. “While there will be some lingering questions on dose response and the magnitude of benefit for admilparant,” the success of the lower dose is “likely to open a blockbuster opportunity,” William Blair analyst Matt Phipps wrote in a separate note.
Bristol Myers shares initially climbed more than 6% in pre-market trading before reversing course and settling into a roughly 4% loss. The data were also taken as bad news by investors of Contineum Therapeutics, which has a different LPA1 drug in Phase 2 testing. Contineum’s stock price fell about 30% in Monday morning trading.
Bristol Myers separately claimed success in a different late-stage study testing a radiopharmaceutical called RYZ-101 against certain neuroendocrine tumors. The drugmaker gained control of RYZ-101 in a $4.1 billion buyout of RayzeBio.
