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The subject of rumours earlier this year that Eli Lilly was interested in a multibillion-dollar takeover, Abivax this week unveiled a key trial readout that investors had been waiting to see for its ulcerative colitis (UC) candidate obefazimod before a planned FDA filing.Instead of celebrating, however, investors sent the French biotech's shares tumbling more than 32% on Tuesday after results from the ABTECT maintenance trial revealed several cancer cases among patients receiving the higher dose of the oral miR-124 enhancer. The safety concerns overshadowed what was otherwise a successful Phase III readout, according to analysts.The study enrolled 580 patients who had responded to treatment in the ABTECT-1 and ABTECT-2 induction trials reported last year. Those earlier studies showed that the higher 50-mg dose of obefazimod had met the primary endpoint of clinical remission at week eight, with pooled remission rates of 16.4% versus placebo.Remissions rates around 40%On Monday, Abivax announced that after 44 weeks of once-daily obefazimod, placebo-adjusted clinical remission rates were 39.3% and 40.3% in the 25-mg and 50-mg dose arms, respectively, achieving the primary endpoint of the maintenance study.Both doses met all key secondary endpoints as well. Placebo-adjusted rates for the lower and higher doses, respectively, were 42.5% and 51% for endoscopic improvement; 31.4% and 37.8% for endoscopic remission; and 35.1% and 38% for corticosteroid-free remission."The totality of the data reinforces obefazimod's potential to meaningfully change the treatment landscape for ulcerative colitis," Chief Medical Officer Fabio Cataldi said in a release Monday. The company plans to submit an FDA filing in the fourth quarter.Seven cancer casesHowever, attention quickly shifted to the trial's safety findings. Among patients receiving the 50-mg dose, investigators reported one case each of prostate cancer, breast cancer and colonic dysplasia, along with four cases of non-melanoma skin cancer (NMSC) divided evenly between basal cell and squamous cell carcinoma.Abivax said the prostate, breast and colon cases were "considered unrelated to treatment by investigators, and no organ-specific clustering was observed." For the skin cancers, the company noted that two cases were judged not or unlikely related to treatment; and of the remaining two cases, one had a prior history of skin cancer. The average age of patients who developed skin cancer was 62 years, compared to 42 years across the broader study population, a difference Abivax said was consistent with age-related risk of NMSC.'Complicates matters'Still, analysts said the findings could pose an obstacle as regulators — and potential M&A suitors — scrutinise the data package. "[The] cancer signal complicates matters," Jefferies analysts said. "Even if unrelated noise, we think the overhang will be real, especially considering absence of other value-inflecting data events over the next [year]."Damien Choplain of Stifel struck a more optimistic tone. "While the malignancy signal cannot be ignored, we view it as a potential labelling overhang rather than evidence of a clear causal safety risk," he said, adding that the efficacy results for obefazimod remained strong. He pointed out that other inflammatory disease drugs, such as AbbVie's oral JAK inhibitor Rinvoq (upadacitinib), carry malignancy warnings yet were nevertheless still commercially successful. Rinvoq itself had sales of $8.3 billion last year.In January, speculation surfaced that Eli Lilly was preparing a bid for Abvivax worth €15 billion ($17.5 billion), with one report suggesting the US pharma was weighing potential regulatory hurdles in France before moving forward.Abivax CEO Marc de Garidel declined at the time to comment on whether Lilly had approached his company, but said it would seek a partner to market obefazimod outside the US. More recently, he indicated that Abivax was in no hurry on the acquisition front despite the takeover chatter.

Dive Brief:Shares of Abivax tumbled Tuesday despite what the company described as landmark Phase 3 data, as safety concerns clouded findings showing its experimental therapy appeared more effective than other marketed drugs for inflammatory bowel disease.After 44 weeks, two different doses of its drug, obefazimod, were associated with placebo-adjusted clinical remission rates of about 39% and 40%, respectively, in patients with moderately to severely active ulcerative colitis. Those figures far surpassed investor expectations and represented what some analysts described as best-in-disease efficacy.However, investigators also detected malignancies in a few drug recipients treated with a higher dose of AbiVaxs drug. AbiVax said those events were deemed unrelated to treatment, werent clustered around a specific organ, and that it aims to file for approval in the fourth quarter. Company shares fell by a third on Tuesday, however, wiping out billions in market value.Dive Insight:AbiVax has had a meteoric rise over the last year thanks to the progress of obefazimod.The drug works differently than other available treatments for inflammatory bowel disease, boosting the expression of an important immune response regulator called miR-124. That approach is meant to dampen the inflammation associated with IBD, but without broadly suppressing the bodys defenses. As a once-daily pill, obefazimod could offer a convenience advantage over many approved IBD therapies, too.Large drugmakers have scooped up several makers of oral immune disease medicines in recent years on the potential that these kinds of drugs might match the potency of injectable therapies. AbiVaxs data has suggested obefazimod may even be superior to injectable counterparts, which typically show placebo-adjusted remission rates in the range of 19% to 32%, wrote Stifel analyst Damien Choplain in a Tuesday client note. Shares once worth less than $10 apiece closed on Monday at nearly $130 amid expectations obefazimod could upend IBD treatment or that AbiVax a rumored buyout target might be acquired along the way.The Phase 3 findings supported that potential, with treatment producing remission rates of around 51% at both tested doses, compared to about 10% for placebo recipients. Those findings met the studys main objective, clearly exceeded expectations, and separate obefamizod from competitors, wrote Leerink Partners Thomas Smith. The drug achieved all of its key secondary study goals, too.But the detection of a handful of malignancies of the prostate, breast and skin appears to have spooked Wall Street investors. While rare, sporadic in nature and of unclear cause, those events introduced uncertainty and represent a signal that cannot be ignored, Choplain wrote.Both analysts rallied to AbiVaxs defense. Smith noted how widely used IBD drugs like Stelara and Entyvio carry language on their prescribing information that notes the theoretical risk of a malignancy. Even if the Food and Drug Administration were to require similar labeling for obefamizod, the drug would remain commercially competitive given the compelling efficacy results and sales trajectory of other medications, he added.Choplain also noted how AbbVies Rinvoq, a different type of oral IBD medicine, has a boxed warning for malignancy but still generated $8.3 billion in sales last year. The drugs approval is likely, assuming the full data confirms no causal signal, he added. '