Brensocatib

With the failure of a phase 2 trial of Brinsupri in chronic rhinosinusitis without nasal polyps (CRSsNP), Insmed has discontinued its program to develop the newly approved, first-in-class DPPI inhibitor in the indication. Insmed has come up short in its attempt to expand its newly approved potential blockbuster Brinsupri into a new indication.With the failure of a phase 2 trial of Brinsupri in chronic rhinosinusitis without nasal polyps (CRSsNP), the New Jersey company has discontinued its program to develop the first-in-class DPPI inhibitor for the disorder, which would have brought a large patient population.The study did not meet any of its primary or secondary endpoints in either of the 10 mg or 40 mg treatment arms.As for the primary endpoint, Mizuho analyst Graig Suvannavejh, Ph.D., wrote in a note to investors that Brinsupri “failed spectacularly,” citing that patients had better outcomes with placebo than with either of the treatment doses.“Given that there are no animal models in this disease, the purpose of this proof-of-concept study was to determine if brensocatib could provide treatment benefit to patients with CRSsNP,” Martina Flammer, M.D., Chief Medical Officer of Insmed, said in a release. “While we are disappointed in the results, they provided us with a clear answer.”As a result, Mizuho sliced its peak annual sales projection for Brinsupri across all potential indications from $16 billion to $11 billion.After Insmed reported the failure late Wednesday, the company’s share price had fallen by 16% by mid-morning on Thursday.The lone positive from the trial is that Brinsupri was well-tolerated, with no new safety signals, including in the 40 mg arm, which is the highest dose the company has studied, exceeding its approved 10 mg and 25 mg dosages. In August, the FDA signed off on Brinsupri as a treatment for the rare respiratory disorder non-cystic fibrosis bronchiectasis (NCFB). In November, the European Union followed suit with a similar nod.In the same Dec. 18 release, Insmed announced the acquisition of Opsidio’s OpSCF, an investigational monoclonal antibody now known as INS1148. The company did not disclose financial details about the deal.Private Pennsylvania biotech Opsidio has been developing the antibody as a treatment for chronic inflammation. The program targets stem cell factor and was being developed in partnership with AbbVie.Opsidio was conducting a phase 2a trial of the asset in patients suffering from moderate-to-severe atopic dermatitis. Insmed is now picking up the program, which it believes has first-in-class potential for respiratory, immunological and inflammatory diseases with high unmet need, according to the release.Insmed said it plans on running phase 2 studies for INS1148 initially in interstitial lung disease and moderate-to-severe asthma. In the CRSsNP trial, which enrolled 288 participants across 104 sites, patients were randomized 1:1:1 for placebo, 10 mg Brinsupri and 40 mg Brinsupri. They received treatment for 24 weeks, which included the nasal spray background therapy mometasone furoate.As for the primary endpoint, the study used the patient-reported Total Nasal Symptom Score (TNSS), a 12-point measurement of a variety of nasal issues such as sneezing, runny nose, congestion and sleep disruption. While those on placebo reported a 2.44-point reduction from baseline, those in the 10 mg group reported a 2.21-point reduction and those in the 40 mg arm saw a 2.33-point reduction.Insmed is also investigating Brinsupri in the inflammatory skin disorder hidradenitis suppurativa (HS), with results from a phase 2 trial expected in the first half of next year. The company maintains an “optimistic view” in the indication because HS is a “strongly neutrophilic disease,” Muzuho reported, based on discussions with management on Wednesday night. Insmed has another lung disease drug on the market, Arikayce, which treats patients with mycobacterium avium complex (MAC). The amikacin liposome inhalation suspension treatment was approved in 2018 and generated sales of $364 million last year. In the first half of next year, Insmed expects to read out results from a trial of Arikayce as a first-line treatment for the disorder.  The company also boasts a promising treatment for pulmonary arterial hypertension (PAH). In June, after reporting eye-opening phase 2 results for treprostinil palmitil inhalation powder (TPIP), Insmed saw a 27% spurt in its share price.

Insmed said it is discontinuing work on Brinsupri in a form of chronic rhinosinusitis after the inflammation drug failed a Phase 2b study. The Bridgewater, NJ-based biotech also said Wednesday it’s bringing in an old AbbVie asset to treat respiratory diseases, and laid out Phase 2 plans for that drug. The company’s shares $INSM , which have more than doubled in the past year, fell 15% Thursday morning. The Phase 2b study for Brinsupri looked at two different doses in chronic rhinosinusitis without nasal polyps (CRSsNP), a common form of long-term sinus inflammation. The drug at both doses showed essentially no difference from placebo in improving sinus symptoms. The drug, which is known generically as brensocatib, also failed to hit secondary efficacy endpoints. “Given that there are no animal models in this disease, the purpose of this proof-of-concept study was to determine if brensocatib could provide treatment benefit to patients with CRSsNP,” Insmed chief medical officer Martina Flammer said in a press statement . “While we are disappointed in the results, they provided us with a clear answer.” Cantor analysts wrote to clients that peak sales of $500 million to $1 billion of Brinsupri in chronic rhinosinusitis were expected, and Wednesday’s trial failure “limits [brensocatib]’s potential as a pipeline-in-a-product story.” Before this study fail, Insmed had been having a whale of a year. The company was valued at over $40 billion before the negative study that sent its stock down. The drug developer in June reported promising results from a pulmonary arterial hypertension drug, and raised $750 million in one of the largest stock offerings of the year after the readout. Then, the FDA approved Brinsupri in August to treat a chronic respiratory disease called bronchiectasis, marking the first approval for a DPP1 inhibitor. The drug is meant to quell inflammation, and Insmed is also studying it in a skin condition called hidradenitis suppurativa. That Phase 2 study is expected to read out in the first half of next year. Insmed also acquired an antibody it’s calling INS1148, which targets stem cell factor 248 — a form of a growth factor that’s been implicated in inflammation. The old AbbVie drug was being developed by a private biotech called Opsidio. Insmed said it plans to study INS1148 in interstitial lung disease and moderate-to-severe asthma in Phase 2 trials. Insmed told Endpoints News it paid Opsidio $40 million upfront and the deal includes “customary” milestones and “mid to high single digits” in royalty payments.