Bristol Myers wins two Phase 3 trials in one day, but a missed high dose sends its shares lower

Bristol Myers Squibb reported two successful late-stage trials on Monday, but its stock still fell 2.6% after the company said the higher dose of its experimental lung-fibrosis pill missed statistical significance and it released no detailed numbers for either study.

Two wins, one caveat

Bristol Myers Squibb put out two pieces of good trial news on Monday. Its experimental pill for idiopathic pulmonary fibrosis, admilparant, met the main goal of a late-stage study of roughly 1,255 patients. Separately, RYZ101, the radioactive cancer drug at the center of its RayzeBio purchase, beat standard treatment on progression-free survival at a planned interim look.

The stock still fell. Shares opened higher and touched $60.68, about 2.6% above Friday's $59.12 close, then reversed and finished at $57.58, down 2.6%. About 22.6 million shares changed hands, more than twice Friday's volume.

The reason sits in one sentence of the lung-disease release. ALOFT-IPF tested two doses against placebo. The 60-milligram dose, taken twice a day, produced a statistically significant benefit on the change in forced vital capacity — a standard measure of how much air a patient can exhale — after 52 weeks. The 120-milligram dose also slowed that decline, the company said, but the result was not statistically significant.

Why the higher dose matters

A drug that works at a low dose but not a high one invites questions, and the company has not yet released the numbers that would answer them. Bristol said it will complete a full evaluation, talk with health authorities about planned regulatory filings and present detailed results at a future medical meeting.

Analysts split on how much the missing dose response matters. In notes cited by BioSpace, Leerink called the result mixed and said the lack of a dose response raises questions about the drug's profile, even if the data could be enough for approval. BMO Capital Markets said the trial validates the drug's mechanism in a large registrational study but is unlikely to be viewed as entirely clean. William Blair was the most upbeat, estimating $1.3 billion in admilparant sales for the disease in 2032.

Safety was the other overhang. Earlier this month Bristol disclosed a death from multi-organ failure after acute liver injury in the admilparant program; William Blair said management told it the patient was in the 120-milligram arm and that an adjudication committee found the death unlikely to be related to the drug. On Monday the company said both doses were well tolerated and that discontinuations due to side effects were low and similar to placebo. Truist wrote that this addressed the liver concern. Bristol did not give a breakdown of individual safety events.

The commercial case rests on how few options patients have. Bristol says about 1.4 million people live with idiopathic pulmonary fibrosis worldwide, that pulmonary fibrosis has a median survival of three to five years after diagnosis, and that very few new therapies have been approved in more than 10 years. Admilparant blocks a receptor called LPA1, and Bristol calls it a potential first-in-class drug. A second Phase 3 study, ALOFT-PPF, in about 1,057 patients with progressive pulmonary fibrosis, is fully enrolled, with topline results expected in early 2027.

RayzeBio's first big test

The cancer readout carries a different kind of weight. Bristol agreed in December 2023 to buy RayzeBio for $62.50 a share in cash, an equity value of about $4.1 billion, to get into radiopharmaceuticals — drugs that carry a radioactive payload directly to tumor cells. RYZ101 was RayzeBio's lead program.

ACTION-1 enrolled patients with gastroenteropancreatic neuroendocrine tumors, a rare cancer of the gut and pancreas, whose disease had progressed after lutetium-177 radiopharmaceutical therapy, an approved treatment for these tumors. Patients received either RYZ101, which uses the alpha-emitting isotope actinium-225, or their doctor's choice of higher-dose or more frequent somatostatin analogue injections, everolimus or sunitinib. The study met its primary endpoint, with blinded central reviewers judging a statistically significant and clinically meaningful improvement in progression-free survival, and safety was in line with what was already known about the drug.

RayzeBio's chief medical officer, Amreen Husain, said these are the first Phase 3 results for a targeted radiopharmaceutical built on an alpha-emitting isotope, in any disease. The FDA granted RYZ101 orphan drug status for these tumors in August, and the company plans to talk with the agency about next steps toward a filing. Patients in the trial will keep being followed for overall survival. As with admilparant, Bristol did not say how large the benefit was.

The patient population is small: about 18,000 people in the United States are diagnosed with these tumors each year, according to the company. The strategic value is proof that the actinium platform Bristol paid for can win a randomized late-stage trial.

The rival that fell harder

The sharpest reaction came at Contineum Therapeutics, whose lead drug, PIPE-791, also targets LPA1 and is in a mid-stage pulmonary fibrosis study. Contineum shares closed down about 36% at $8.57, from $13.38 on Friday. William Blair argued the Bristol data were encouraging for other LPA1 developers, Contineum in particular. Investors sold anyway after the mixed dose result.

The full data will decide

For Bristol, the readouts arrive as it tries to restock its pipeline before it loses exclusivity on its best-selling drugs, Opdivo and Eliquis. More tests are close behind: a Cobenfy readout in Alzheimer's disease psychosis in early 2027 and topline results next year for milvexian, an oral blood thinner partnered with Johnson & Johnson and being tested in atrial fibrillation.

The next real information on Monday's two drugs will come with the full data. For admilparant, that means the size of the lung-function benefit at 60 milligrams, how the 120-milligram arm actually performed and the liver-safety detail. For RYZ101, it means the progression-free survival gap and, later, overall survival. Until then, both are positive topline results from the company, not approvals.