FDA Approves Nintedanib for SSc-ILD

The US Food and Drug Administration (FDA) has approved nintedanib (Ofev) for the treatment of interstitial lung disease associated with systemic sclerosis or scleroderma (SSc-ILD).

The approval makes the Boehringer Ingelheim oral tyrosine-kinase inhibitor the first therapy approved for patients with the rare lung condition.

Scleroderma is a rare, life-threatening disease that thickens and scars tissue throughout the patient’s body, including in the lungs and other organs. ILD—one of the most common manifestations of scleroderma—is the leading cause of death associated with the condition, often results in patient loss of pulmonary function.

Of the approximate 100,000 US cases of scleroderma, about half of the patients have SSc-ILD.

The benefit of nintedanib was proven in the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial, in which patients were assessed over 1 year with 150 mg twice-daily therapy or placebo. Investigators—led by Oliver Distler, MD, of the Department of Rheumatology at the University Hospital of Zurich, and Kristin B. Highland, MD, of the Respiratory Institute at the Cleveland Clinic—assessed for primary endpoints of annual forced vital capacity (FVC) decline over 52 weeks.

Adjusted annual rate of FVC decline was -52.4 ml per year for patients on nintedanib—a notable reduction from the -93.3 ml average decline in patients on placebo (41 ml; 95% CI, 2.9 — 79.0; P = .04).

In an interview with MD Magazine® while at the American Thoracic Society (ATS) 2019 International Meeting this year, Highland explained the benefit of reduced FVC decline: it indicates retained lung function in patients, and increases their chance of survival.

“So forced vital capacity is really our best surrogate for overall lung function and it does track with what we see on chest CT; it does track with survival,” she explained. “This is an orphan disease—it would be a little difficult to power design the study to be a mortality study. So first vital capacity, at this point in time, is probably our best surrogate in in all comers with interstitial lung disease.”

This July, the FDA’s Arthritis Advisory Committee voted 10-7 to recommended the approval of nintedanib based on the findings of the SENSCIS trial. Prior to the committee support, it was granted Priority Review.

An ongoing continuation trial, SENSCI-ON, features a “vast majority” of the phase 3 study’s population, Highland said. The data is anticipated to help informed treatment effect stability measures while following patients for a few years.

“We'll have that data,” Highland said. “I anticipate that there'll be real-world registries of scleroderma patients that get treated.”