The U.S. Food and Drug Administration was forced to draw a line in the sand on Monday, with its approval of neratinib (Nerlynx), an adjuvant treatment for patients with early stage HER2-positive breast cancer.
Manufactured by Los Angeles, California-based Puma Biotechnology, neratinib polarized experts with its Phase 3 data showing marginal efficacy and high rates of side effects. Many have questioned whether the benefits really outweigh the risks.
On Monday, FDA (somewhat) settled that debate by granting it marketing approval.
A tyrosine kinase inhibitor, neratinib works by blocking multiple enzymes that would otherwise promote cell growth. It’s indicated for HER2-positive tumors, a gene expressed in approximately 15 percent of breast cancers.
Rather than treating the disease, neratinib is designed to lower the risk of a patient’s cancer recurring after treatment with trastuzumab (Herceptin). As such, it’s prophylactic: A majority of women wouldn’t have experienced a recurrence either way.
In a pivotal trial, more than 2,800 patients were randomized to receive neratinib or a placebo. After two years, Puma reported that 94.2 percent of patients treated with the active drug had not experienced cancer recurrence or death, compared to 91.9 percent of patients receiving placebo — a difference of 2.3 percent.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
As noted by Forbes’ Matthew Herper, that means that if 100 women were treated for two years, two would be spared cancer as a result of taking Puma’s drug.
On the other hand, nearly all patients experienced side effects, primarily diarrhea. In one study 96 percent had some degree of diarrhea and 40 percent of patients had Grade 3 diarrhea, which “may require treatment in the hospital or clinic.” Grade 4 is deemed life-threatening.
Experts from the Oncologic Drugs Advisory Committee (ODAC), which reviewed the merits of the drug in May, noted that these side effects were a concern “given the frequent dose interruptions, reductions and discontinuations observed.”
Puma’s VP of Clinical Development Susan Moran countered that the side effects were largely contained to the first eight days of treatment and ODAC ultimately voted 12-4 in favor or recommending the drug.
It was yet another inflection point for shares of the Nasdaq-listed company ($BPYI). Even for a biotech, its stock has experienced turmoil over the years as investors speculated over the drug’s potential to make it to the market. Trading was suspended on Monday in anticipation of FDA’s decision.
The question now is whether Puma can prove value to payers, physicians, and patients. Ultimately, only the latter can truly determine whether the benefits outweigh the risks. They now have the power to decide.
According to the National Cancer Institute (NCI), breast cancer is the most common form of cancer in the United States. Approximately 252,710 women will be diagnosed with breast cancer this year and 40,610 will die of the disease — though it’s important to note that men can also be affected.
Photo: Michail_Petrov-96, Getty Images
