Novartis Drug Wins FDA Approval for Lung Cancers With Specific Mutation

Xconomy National — 

As cancer research reveals the genetic basis of the disease, pharmaceutical companies are pursuing targeted therapies that address certain groups of patients. One such drug from Novartis won FDA approval Wednesday, making it the first therapy cleared by the agency to treat patients whose non-small cell lung cancer (NSCLC) carries a certain genetic mutation.

The FDA’s decision for the drug, capmatinib (Tabrecta), was made on an accelerated basis, a pathway the regulator reserves for drugs that address life-threatening conditions. In exchange for a speedy approval based on less data, Novartis (NYSE: NVS) will likely need to conduct additional studies to confirm the drug’s benefit to patients.

Approval of capmatinib covers patients whose non-small cell lung cancer has spread to other parts of the body. Those tumors must have a particular to mutation in the gene that makes MET, a protein involved in sending signals that regulate cell growth and survival. The mutant version of the protein is produced by exon skipping, in which a cell’s protein-making machinery misses certain pieces of genetic code.

NSCLC accounts for about 84 percent of lung cancers, according to the American Cancer Society. One of the critical events that lead to the spread of this cancer to other parts of the body is MET exon 14 skipping. The FDA says mutations leading to this type of exon skipping are found in 3 to 4 percent of lung cancer patients. The Novartis drug, a kinase inhibitor, blocks a key enzyme, which in turn helps to stop tumor growth, according to the FDA. The regulator on Wednesday also approved a companion diagnostic from Foundation Medicine that tests for the genetic mutation that leads to MET exon 14 skipping.

The FDA based its capmatinib decision on the results of an open-label Phase 2 study that evaluated the drug in 28 patients who have never been treated for their lung cancers as well as 69 patients who previously received treatment. The main goal was to assess the overall response rate to the twice-daily pill, assessed by measuring tumor shrinkage.

In the group of 28 patients who had never been treated, 68 percent showed some response to the therapy. Of those, 4 percent showed a complete response. The FDA said that 47 percent of patients in this group had a response to the Novartis therapy that lasted a year or longer. In the group of 69 previously treated patients, the overall response rate was 41 percent. All of those responses were partial. The FDA said that 32.1 percent of patients in this group had a response to treatment that lasted 12 months or longer.

The most common side effects reported from the study included leg swelling, nausea, fatigue, vomiting, shortness of breath, and decreased appetite. The FDA cautions that capmatinib may also lead to more serious side effects, such as a group of conditions that cause scarring in the lung, as well as inflammation of tissue in that organ. If those problems emerge, the FDA says treatment should stop. The drug may also lead to liver damage, and the agency advises physicians to monitor a patient’s liver function before starting therapy and throughout the course of treatment.

Capmatinib was discovered by scientists at Incyte (NASDAQ: INCY). In 2009, the Wilmington, DE-based company entered a multi-drug partnership with Novartis. The deal granted the Swiss pharmaceutical giant global development and commercialization rights to capmatinib, leaving Incyte the option of co-developing and co-promoting the drug in the US. Ruxolitinib (Jakafi), another drug covered by the pact, was approved for myelofibrosis in 2011.

The partnership initially paid Incyte $210 million. Milestones could bring the biotech up to $1.2 billion more. Incyte says approval of capmatinib triggers a $70 million milestone payment. According to the terms of the agreement, Novartis is responsible for all commercialization costs for the lung cancer drug.

Lung cancer metastasis image by the National Cancer Institute