Do investors want the good news, or the bad news first? Bellus went with the good news, sharing that its chronic cough contender hit the primary endpoint in a Phase IIb trial, lining it up for a Phase III study in the second half of next year where it could pose stiff competition for Merck.
Amidst all the commotion, the Canadian biotech also revealed that the same candidate flunked a proof-of-concept trial in atopic dermatitis, and the company will now steer the program away from pruritic conditions.
Evercore ISI’s Josh Schimmer said the strong cough readout ‘more than offsets this miss,’ and investors seemed to agree — Bellus’ stock $BLU was up more than 60% Monday morning.
At two dose levels, BLU-5937, a P2X3 receptor antagonist, reduced patients’ chronic cough frequency by 34% compared to placebo at day 28 (p ≤ 0.005), Bellus announced Monday. Patients also reported few taste-related side effects, with 6.5% and 4.8% of participants experiencing taste alterations in the 50 mg and 200 mg groups, respectively.
A smaller, 12.5 mg dose did not reach statistical significance, reducing cough by 21% compared to placebo, but with a p-value of p=0.098.
The Phase IIb trial, dubbed SOOTHE, enrolled 249 patients across four arms (three dose levels and a placebo). Overall, the safety profile was similar to placebo, Bellus reported, with no treatment-emergent serious events and no reported complete or partial losses of taste.
‘Obviously this is a short trial,’ CMO Catherine Bonuccelli said during a call with investors on Monday. ‘You’re still seeing improvement out to the 28 days. So I do think you could see continued improvement when we extend further, and that of course will be tested in Phase III.’
The readout is welcome news for Bellus, which suffered a huge setback when BLU-5937 flunked a Phase II trial back in July 2020. The biotech tested four different doses in the mid-stage study, all of which fell short of the mark for placebo-adjusted reductions in coughing — several by a wide margin.
CEO Roberto Bellini attempted to shift the focus to a subgroup of ‘high cough count patients,’ where BLU-5937 did hit statistical significance. Those were patients who experienced a baseline median average of 32.4 coughs per hour.
SOOTHE looked at patients with at least 25 coughs per hour, a criterion that was not included in the older study but was an area where some data had suggested the program might be more effective.
Bellus plans on meeting with the FDA in Q2, which should set it up to launch into Phase III sometime in the second half of next year.
‘With no specific treatments approved for refractory chronic cough, patients and physicians struggle to manage this condition that significantly impacts the quality of life of those afflicted,’ principal investigator Jaclyn Smith said in a statement.
The drug could pose tough competition to Merck’s P2X3 receptor antagonist gefapixant, which is currently under FDA review and could win an approval by the end of the year. While it’s impossible to directly compare two trials, Merck’s candidate registered an 18.5% estimated relative risk reduction in 24-hour cough frequency (p=0.041). Gefapixant’s PDUFA date is coming up on Dec. 21.
There’s also Bayer’s eliapixant, which reduced 24-hour cough frequency by 27% compared to placebo after 12 weeks in a Phase IIb trial, the company said back in September. In an earlier Phase IIa study, Shionogi’s sivopixant reduced 24-hour cough rate by 30.9% (p=0.0386), according to results published in the European Respiratory Journal.
Meanwhile, it’s the end of the road for Bellus’ other BLU-5937 program in atopic dermatitis. The drug failed to significantly reduce itching in patients on the weekly mean Worst Itch-Numeric Rating Scale, according to Bellus. And while the drug was well-tolerated, the company’s putting that program back on the shelf.
https://endpts.com/bellus-soars-on-positive-mid-stage-readout-for-its-merck-cough-rival-despite-a-failure-in-atopic-dermatitis/
