A low-dose win could derisk a regulatory pathway for BMS’ LPA1 antagonist in idiopathic pulmonary fibrosis after a recently reported patient death, but a miss at the higher dose leaves analysts awaiting full data.
Bristol Myers Squibb’s late-stage lung disease asset has scored in a low-dose cohort while failing to improve exhalation capacity at a higher dose, leaving analysts wanting more.
The Big Pharma’s LPA1 antagonist, dubbed admilparant, ultimately met the primary endpoint of an idiopathic pulmonary fibrosis (IPF) study at the 60-mg dose, demonstrating a statistically significant improvement over placebo in patients’ absolute change in forced vital capacity (FVC) from baseline at week 52. But the 120-mg dose failed to reach statistical significance on the same measure. The company didn’t provide the data behind the results.
Leerink called the findings “mixed,” writing in a Monday note that the ALOFT-IPF Phase 3 results “could be sufficient to support admilparant regulatory approval, but the lack of dose response raises questions about its profile.
“We await detailed results to better understand the drug’s efficacy,” the analyst added.
William Blair was more bullish, estimating $1.3 billion in admilparant sales for IPF in 2032.
“While there will be some lingering questions on dose response and the magnitude of benefit for admilparant from the ALOFT-IPF study, we believe the success of the 60 mg dose is likely to open a blockbuster opportunity given we view the novel mechanism and non-overlapping toxicities with current therapies in IPF as positive for combination approaches,” William Blair wrote Monday.
BMS is still evaluating the data and plans on meeting with heath authorities to “support planned regulatory submissions,” according to its news release. Detailed results from the trial are expected for presentation at an unnamed future medical meeting.
The pharma’s stock fell 3% within the first hour of trading on Monday, from $60.11 per share at open to $57.14.
As for safety, BMS said the drug was well-tolerated across both doses in ALOFT-IPF and noted that discontinuations due to adverse events were comparable to placebo. The Big Pharma did not provide details on safety events, such as hypotension or liver toxicity risk. Earlier this month, BMS reported a death due to multi-organ failure after acute liver injury in its ALOFT program, which includes another Phase 3 trial for progressive pulmonary fibrosis that is expected to read out early next year.
BMS management told William Blair that the deceased patient was in the 120-mg admilparant arm, and an adjudication committee determined the death was unlikely related to study treatment, according to a Monday note from the analysts.
A limited number of liver events were observed in the ALOFT program, BMS told BioSpace earlier this month. Most were mild, transient and linked to other medical conditions or in patients taking other medications that have known liver risk factors.
“A key concern recently has been around liver safety and we think the data reported showing admilaparant [sic] was well tolerated across both doses with AE associated discontinuations low and similar to [placebo] on both active arms addressed this overhang,” Truist wrote Monday morning.
“All in, today’s update points to a derisked regulatory submission path for Bristol pending full data release,” BMO Capital Markets’ Evan Seigerman and colleagues wrote in a Monday investor note.
“Importantly, the result validates the LPA1 mechanism in a large registrational study; however, the data are unlikely to be viewed as entirely clean given the 120mg arm slowed FVC decline but failed to achieve statistical significance,” BMO said.
Pulmonary fibrosis is a chronic, life-threatening disease that occurs when lung tissue becomes irreversibly damaged, impacting the organ’s function. William Blair noted that BMS’ trial win is likely a positive for Contineum Therapeutics, which is also developing an LPA1 for pulmonary fibrosis and chronic pain.
As for BMS’ admilparant, the next step will be about “understanding the magnitude of benefit, consistency across subgroups and the explanation for the unexpected dose-response relationship,” the BMO group wrote Monday.
“Taken together, we view ALOFT-IPF as an incremental positive as we set up for a catalyst rich period,” the analysts added.
The Big Pharma is expecting a Cobenfy readout in Alzheimer’s disease psychosis in early 2027, plus topline results next year for milvexian, a Johnson & Johnson–partnered investigational oral factor XIa inhibitor, in atrial fibrillation.
Last month, Seigerman told BioSpace that he was bearish on BMS’ plans to restock its pipeline as exclusivity loss looms for best-selling drugs Opdivo and Eliquis.
“We remain on the sidelines as we continue to be wary of the binary risk setup for one of our major pharma names,” he wrote Monday.
BMS shared the IPF data on the same day it announced a Phase 3 win for RYZ101, the centerpiece of its $4.1 billion RayzeBio acquisition. The investigational radiopharmaceutical significantly improved progression-free survival for patients with gastroenteropancreatic neuroendocrine tumors.
