FDA Grants Breakthrough Therapy Status to Ofev for Sarcoidosis, Other ILDs

The U.S. Food and Drug Administration (FDA) has granted the designation of breakthrough therapy to Ofev (nintedanib) for the treatment of patients with sarcoidosis and other types of progressive fibrosing interstitial lung diseases (ILDs).

The breakthrough designation is given to medications that provide significant advantages over currently available options. It is intended to accelerate the development, review, and approval of medications to treat serious or life-threatening conditions.

ILDs comprise more than 200 disorders, including sarcoidosis and pulmonary fibrosis — a condition in which the lungs become irreversibly scarred and cease to work properly.

Ofev is an approved anti-fibrotic therapy (a medication that reduces lung tissue scarring), marketed by Boehringer Ingelheim, for the treatment of idiopathic pulmonary fibrosis (IPF) and scleroderma. The medication works by interfering with the PDGF and FGF signaling pathways, known to be overly active in patients with lung fibrosis (scarring).

The breakthrough designation for the treatment of progressive ILDs was granted based on findings from the Phase 3 INBUILD trial (NCT02999178).

The study, sponsored by Boehringer Ingelheim, enrolled 663 adult patients with progressive ILDs other than IPF who were randomly assigned to receive either Ofev (administered at a dose of 150 mg twice a day) or a placebo for one year (52 weeks).

The trial’s primary endpoint was to determine the annual rate of lung function decline by measuring changes from baseline to week 52 in patients’ forced vital capacity (FVC, the amount of air a patient is able to exhale after taking a deep breath).

Secondary endpoints included assessing changes from baseline to week 52 in the participants’ health-related quality of life, as well as the time patients lived until showing signs of disease progression, experiencing an acute exacerbation or death.

Findings from the INBUILD trial — recently presented at the European Respiratory Society (ERS) International Congress, and published in the New England Journal of Medicine — showed that it met its primary endpoint, with Ofev reducing patients’ lung function decline by 57% over the course of one year compared with the placebo.

The most common adverse event seen during the trial was diarrhea, which was more frequent among patients treated with Ofev (66.9%) than among those treated with the placebo (23.9%). This finding was consistent with observations from previous studies.

“We believe Ofev may help address an unmet medical need by providing a therapy for patients across a spectrum of ILDs with a progressive phenotype,” Thomas Seck, MD, senior vice president of medicine and regulatory affairs at Boehringer Ingelheim, said in a press release.

“We are encouraged by this breakthrough therapy designation and look forward to working closely with the agency to offer this therapy to patients for which there are no FDA-approved treatment options,” Seck added.

One of the expectations of experimental medications that receive the status of breakthrough therapy is that sponsors launch a compassionate use protocol to make the investigational treatment available to patients who may benefit from it. Boehringer Ingelheim has already launched a compassionate use program that allows those with progressive ILDs who are not eligible or unable to participate in clinical trials to have access to Ofev.

According to Boehringer, the company has also submitted regulatory applications for Ofev to other regulatory bodies, including the European Medicines Agency.