For the second time in a span of four months, Insmed’s Brinsupri has come up short in a mid-stage trial designed to expand its use into a new indication.
The New Jersey biotech revealed that a phase 2b study of Brinsupri in adults with moderate to severe hidradenitis suppurativa (HS) has failed to achieve its primary or secondary endpoints for either of its 10 mg or 40 mg once-daily treatment arms. With the result, the company will terminate the program.
The flop comes after Insmed reported the misfire of another Brinsupri trial, testing the first-in-class dipeptidyl peptidase 1 (DPP1) inhibitor in patients with chronic rhinosinusitis without nasal polyps (CRSsNP).
That phase 2 study was similarly unsuccessful, as it failed to hit any of its primary or secondary endpoints with either the 10 mg or 40 mg dose. The result was conclusive enough that Insmed also discontinued Brinsupri’s development in that indication.
In the HS study of 214 patients, Brinsupri failed to top placebo, with those in the 10 mg and 40 mg treatment arms experiencing reductions in their total abscess and inflammatory nodule (AN) counts of 46% and 40%, respectively, compared to 57% in the control group. HS is an inflammatory skin condition that causes painful lumps, abscesses and scarring in the sweat gland areas.
Treatment-emergent adverse events (TEAEs) were more prevalent in the 10 mg arm, at 55%, than in the placebo (46%) or 40 mg (43%) groups, with three serious TEAEs among those in the 10 mg group compared to one each in the other treatment arms.
A lack of established animal models in HS “makes clinical development particularly challenging” in the indication, Insmed’s chief medical officer, Martina Flammer, M.D., said in a release.
“While we are disappointed in the results, we hope that insights gained from this study will contribute to the broader scientific understanding of HS,” Flammer added.
The "silver lining" of the trial, according to analysts at Mizuho Securities, is that it confirmed Brinsupri's "excellent safety/tolerability profile."
Insmed’s failure in the HS study “does not come as a surprise, given the challenges in HS clinical trials (particularly due to high placebo rates) and the lack of preclinical evidence to support DPP1 inhibition in the indication,” Matt Phipps, Ph.D., an analyst with William Blair, wrote in a note to clients.
With expectations “very low” for the readout, there is no change to Insmed’s valuation, Phipps said, adding that he anticipates “minimal impact,” on the company’s shares.
Insmed’s share price traded up nearly 1% before U.S. markets opened on Wednesday.
By contrast, when Insmed revealed in December that it had flunked in CRSsNP—an indication that would have brought a large patient population—analysts from Mizuho sliced their peak annual sales projection for Brinsupri from $16 billion to $11 billion.
Brinsupri was approved in August of last year as a treatment for a chronic lung condition, bronchiectasis. Despite being on the market for just four-plus months, Insmed reported Brinsupri’s sales at $173 million last year. Consensus estimates for first-quarter sales are at $198 million, according to Visible Alpha.