Physicians unsure about new IPF drugs

February 10, 2015

While physicians laud FDA’s approval of nintedanib (Ofev) and pirfenidone (Esbriet) for treating idiopathic pulmonary fibrosis (IPF)-the first approved medications to treat the disease in the United Sates-they don’t know how to use them.

While physicians laud FDA’s approval of nintedanib (Ofev) and pirfenidone (Esbriet) for treating idiopathic pulmonary fibrosis (IPF)-the first approved medications to treat the disease in the United Sates-they don’t know how to use them.

In mid-October, FDA approved Boehringer Ingelheim’s nintedanib and InterMune’s pirfenidone after-trial data showed that they slowed the decline in forced vital capacity and reduced progression of the disease. Pirfenidone is already available in Europe, Canada, Japan and other countries. FDA received criticism after initially rejecting InterMune’s pirfenidone in 2009.

“There is a lot of excitement here. For 50 years, there was no approved therapy, prior to [these recent approvals]. Then, 2 drugs were approved on the same day,” said Imre Noth, MD, professor of medicine and pulmonologist at the University of Chicago Medical Center. The previous available drugs physicians used to help manage IPF, such as azathioprine and prednisone, were unfortunately harming IPF patients, Noth said.

Other commonly prescribed drugs were cyclophosphamide (Cytoxan), a chemotherapy agent that can suppress inflammation, and mycophenolate mofetil (Cellcept and Myfortic), which modulates the immune system.

Since there were no drugs approved specifically for IPF, physicians previously focused on managing comorbid      dities-around one-third of IPF patients typically die of another disease, according to Noth. “If we made sure their hearts were in good condition, managing conditions such as hypertension and diabetes…then we can make them feel better.”

While the approval of pirfenidone and nintedanib is a major advancement for treating IPF, physicians are wary about the ways to utilize the drugs. “It poses a really challenging issue for the community, because there is no guidance about how these drugs should be used or when they should be used,” said Kevin Gibson, MD, professor of medicine and clinical director of the Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease at the University of Pittsburgh Medical Center.

Both drugs have been shown to slow the rate of profession of the disease in trials, but do not cure IPF, Gibson cautioned. “The data is probably driven by a group of 30% to 35% of the patients who responded [to the medications].”

“I would not recommend them for patients who are very stable,” Gibson agreed. “It is unclear if patients on the drugs are going to be more stable on the drugs versus not on them.”

Because the 2 treatments feature fairly equal pricing and efficacy, doctors treating IPF say they will base prescribing decisions on the patient’s progression of the disease and the different side effects of each medication. “There is nothing in the data that suggests one is superior to the other. One has pretty severe gastrointestinal effects, so patients have to take antidiarrheals,” Gibson said.

The most common side effects of nintedanib are diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, decreased weight, and high blood pressure. Pirfenidone side effects include nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness and vomiting, according to FDA.