An Insmed drug developed for a serious chronic lung disorder with no FDA-approved therapies handily beat a placebo in a pivotal clinical trial, that set the stage for a regulatory submission planned for later this year. It could be the first of several. The drug is also in development for other inflammatory conditions, giving the drug multiple opportunities to achieve its blockbuster potential.

The first disease target of the Insmed drug is , a chronic lung disease characterized by excess production of sputum that’s persistently coughed up from the respiratory tract. Patients who have NCFB also experience frequent respiratory infections. There’s no single cause for the disease. “Bronchiectasis” refers to a group of pulmonary diseases with multiple causes that lead to bronchi that become irreversibly damaged and dilated. One cause of bronchiectasis is cystic fibrosis, a lung disorder that has several approved therapies. But with no drug specifically approved for treating NCFB, this condition is managed with drugs or techniques to break up mucus so it can be cleared from the lungs. Antibiotics offer another treatment option.

Insmed’s brensocatib is an oral small molecule formulated as a once-daily tablet. The drug is designed to block dipeptidyl peptidase 1 (DPP1), which activates key enzymes in a type of white blood cell called a neutrophil. These enzymes are associated with a range of inflammatory diseases. When neutrophils accumulate in the airways, the result can be excessive activity from the enzymes, leading to lung damage and inflammation. By blocking DPP1, brensocatib is intended to stop activation of those enzymes. In an , Insmed said the clinical trial results validate this mechanism of action.

Insmed reported that the low dose of brensocatib led to a 21.1% reduction in the rate of pulmonary exacerbations compared to placebo measured at 52 weeks; the high dose achieved a 19.4% reduction. The statistically significant results for both doses met the trial’s main goal. The company also reported both doses achieved statistical significance for secondary goals measuring the time to first pulmonary exacerbation and the increase in odds of remaining exacerbation free over 52 weeks. On another secondary goal measuring a change in forced expiratory volume (a measure of how much air a patient can exhale) in one second, only the high dose posted statistically significant results. Insmed reported its drug was well tolerated by patients. Adverse events reported in the study included the common cold, cough, and headache, but the rates of these problems weren’t much different than what was observed in the placebo arm.

In a note sent to investors on Tuesday, Leerink Partners analyst Joseph Schwartz wrote that there may be a role for both doses as clinicians have told the firm that some neutrophil elastase enzyme may be necessary for proper function and the proper amount of inhibition may be achieved with different doses. As for the drug’s commercial opportunity, Leerink estimates NCFB represents a market of about 450,000 patients in the U.S. That’s just the start.

“Diagnosed NCFB may just be the tip of the iceberg, which could expand several fold with a simple CT scan, potentially identifying more NCFB patients who are currently diagnosed with COPD (chronic obstructive pulmonary disease),” Schwartz said.

While acknowledging that it’s early for predictions, Schwartz said the success of Insmed’s drug in NCFB opens the door to additional indications. The opportunity is reminiscent of the Sanofi/Regeneron Pharmaceuticals drug Dupixent and AbbVie’s Humira, two blockbuster medications with approved uses in several immunology indications, he explained. Besides NCFB, Insmed is conducting a Phase 2b test of brensocatib in chronic rhinosinusitis without nasal polyps. A Phase 2 test of the molecule in the inflammatory skin disorder hidradentis suppurativa is planned to start in the second half of this year.

Brensocatib came from the labs of AstraZeneca, which had advanced the drug through Phase 1 testing. In 2016, Insmed paid $30 million up front to to the small molecule. Another $85 million is tied to the achievement of milestones. If Insmed develops brensocatib for a second indication, it could owe AstraZeneca up to $42.5 million in additional milestone payments starting with the initiation of a Phase 3 clinical trial in the second indication.

Developing brensocatib for more diseases won’t trigger any more milestone payments. However, the makes AstraZeneca eligible for royalties from Insmed’s sales of the drug. The deal also calls for one more $35 million payment when the drug achieves its first $1 billion in annual net sales. AstraZeneca may yet get a bigger piece of the drug’s upside. The agreement gave the pharma giant the option to negotiate a deal for the commercialization of brensocatib in COPD or asthma — two very large respiratory indications. In 2020, AstraZeneca exercised its first option, making it responsible for developing the drug through Phase 2b clinical testing. The deal includes a second option that would allow AstraZeneca to develop the drug in COPD or asthma beyond Phase 2b testing. Insmed retains global rights to the drug in all other indications.

For NCFB, Insmed said it plans to file a new drug application with the FDA in the fourth quarter of this year, setting a preliminary timeline — if all goes well — for a mid-2025 drug launch. The company will also pursue regulatory approvals in NCFB in Europe and Japan. Investors welcomed the drug’s topline results. Shares of Insmed closed Tuesday at $48.06 apiece, up more than 118% from the stock’s closing price Friday ahead of the Memorial Day weekend.

Photo credit: Jackie Niam, Getty Images