The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to Ofev (nintedanib) as a potential therapy for progressive fibrosing interstitial lung disease (ILD) — which also affects systemic sclerosis patients — the treatment’s developer, Boehringer Ingelheim, has announced.
Breakthrough therapy designation is given to investigational compounds that have preliminary clinical evidence showing their therapeutic potential on at least one clinically significant endpoint over existing therapies in serious or life-threatening conditions. This designation is meant to expedite the clinical development (with more intense FDA guidance), review process, and entry into the market (if the treatment shows positive results in clinical trials).
“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,” Thomas Seck, MD, a senior vice president at the company, said in a news release.
ILD is a group of lung disorders in which the tissue in and around the lung air sacs — called the interstitium — becomes inflamed and scarred, affecting breathing and impairing the lungs’ ability to transfer oxygen to the bloodstream. It’s a frequent complication of systemic sclerosis (SSc) — a condition called systemic-sclerosis-associated interstitial lung disease (SSc-ILD) — and the leading cause of death among this patient population. Patients can develop a so-called “progressive fibrosing phenotype” that causes lung fibrosis (scarring), lung function decline, deterioration in quality of life, and early mortality, similar to idiopathic pulmonary fibrosis (IPF), the most common ILD.
Ofev, which works by blocking a group of growth factor receptors involved in lung fibrosis, is an approved treatment for IPF in more than 70 countries. It was also recently approved by the FDA for the treatment of SSc-ILD.
However, no approved treatments are currently available for people with a broad range of progressive fibrosing ILDs.
The breakthrough therapy designation was based on positive data from the Phase 3 INBUILD study (NCT02999178) — the first clinical trial in the field of ILDs to group patients with a variety of progressive fibrosing ILDs, other than IPF, regardless of their primary clinical diagnosis.
The results were recently published in the New England Journal of Medicine in a study titled “Nintedanib in Progressive Fibrosing Interstitial Lung Diseases,” and also presented at the recent European Respiratory Society’s International Congress, in Madrid, Spain.
The randomized, double-blind, placebo-controlled INBUILD study evaluated the safety and effectiveness of Ofev in 663 people with progressive fibrosing ILD. Patients were recruited at 153 trial sites across 15 countries, and randomly assigned to receive either 150 mg of Ofev or a placebo twice daily for a year.
The trial’s primary goal was assessing whether Ofev induced slower lung function decline than a placebo in these patients. Lung function was assessed by the annual rate of decline in forced vital capacity (FVC) — the total volume of air that can be blown forcefully following a full inhalation.
Results showed that after one year of treatment, patients receiving Ofev had a significantly slower decline in lung function (57% less decline in FVC) compared with those receiving a placebo.
Ofev’s overall safety was consistent with the therapy’s known safety profile, with diarrhea being the most frequently reported adverse event (in 66.9% patients, compared with 23.9% in the placebo group). Nausea, vomiting, abdominal pain, decreased appetite, and weight loss were also more frequently associated with Ofev treatment.
“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,” said Seck.
Boehringer has submitted regulatory applications for Ofev for the treatment of people with progressive fibrosing ILD to other regulatory bodies, including the European Medicines Agency.
In agreement with expectations for therapies with breakthrough designations, Boehringer has developed an expanded access program (NCT03843892) to provide Ofev to people with a variety of progressive fibrosing ILD other than IPF, who do not otherwise qualify or are unable to participate in clinical studies. Expanded access is also known as a compassionate use program.