FDA Commissioner Scott Gottlieb has been very public in expressing his desire to provide increased competition and greater choice to American consumers in a bid to drive down prices of prescription medicines. Recently, the agency he oversees took some unusual steps to back up those statements with action.
Last week, the FDA approved the use of the drug olaparib (Lynparza), sold by AstraZeneca and Merck, to include ongoing treatment of patients with recurrent ovarian cancer who have responded to platinum-based chemotherapy. It was widely expected that the drug would receive approval. What was a surprise to many of us was the broad label granted for the drug’s use, as well as the data the FDA used to grant its approval.
First some background: olaparib blocks the activity of the enzyme poly ADP ribose polymerase (PARP), and is termed a PARP inhibitor. In its regulatory filing submitted to the FDA, AstraZeneca showed that the drug was effective in patients who have hereditary BRCA mutations, which include some ovarian, breast, and prostate cancers. While those mutations can make patients more susceptible to cancers, they also make existing tumors more susceptible to treatment with olaparib.
Lynparza was granted accelerated approval for use as a single agent by FDA and European health regulators in December 2014. The FDA approval is in for germline BRCA-mutated advanced ovarian cancer that has received three or more prior lines of chemotherapy.
Less than three months ago, Gottlieb posted the following on the FDA’s blog:
“Too many patients are being priced out of the medicines they need. While FDA doesn’t have a direct role in drug pricing, we can take steps to help address this problem by facilitating increased competition in the market for prescription drugs through the approval of lower-cost, generic medicines.”
In his blog post, Gottlieb refers to the need for more rapid approval of generic medicines. Although innovation in pharmaceutical development is essential because it creates new and sometimes life-saving therapies, he added, access to lower-cost alternatives is also is critical to the nation’s health.
Notwithstanding the fact that olaparib is not a generic medicine, it’s interesting to consider the FDA’s action on Lynparza in the context of Gottlieb’s comments.
While a confirmatory trial (called the SOLO-2 trial) was conducted only in patients with BRCA-mutations, the FDA took the unusual step of approving olaparib to treat both BRCA- and non-BRCA ovarian cancer patients. This is noteworthy in that the FDA usually restricts the product label to the patient population studied in the clinical trial. In addition, in its approval, the FDA relied on data from another study (called Study-19) to support the broad label, but that study actually used a different dose and formulation of olaparib.
The FDA has indicated a willingness to grant broader approvals in orphan diseases, but this decision was uncommon in that U.S. health regulators had already approved another drug, Tesaro’s niraparib (Zejula)—which is also a PARP inhibitor—for the same population of patients with ovarian cancer. Historically, if there’s already another approved drug, there’s less of an argument of an unmet need, and the agency may be more restrictive.
In May, AstraZeneca signaled they would try to seek approval for the broader label, regardless of their BRCA status. Mika Sovak, executive director and Lynparza global development lead, commented that the company would try to convince FDA based upon a “totality of the evidence” approach.
Clearly, FDA was persuaded.
It’s difficult to know how FDA reached its decision. The agency has consistently maintained that patient safety is of paramount importance, and part of its olaparib decision may stem from the fact that Zejula is a drug of the same class and is already approved in the broader population.
With three PARP inhibitors on the market (Rubraca from Clovis, Zejula from Tesaro and Lynparza from AstraZeneca and Merck) and more in development, there’s likely to be intense competition for patients.
With the FDA’s action last week, Tesaro and AstraZeneca/Merck have similar labels, including both the BRCA mutant and non-mutant populations. One way the drug makers will be able to differentiate their products will be with lower prices. All three companies have rolled out similar prices, but the real-world price of the drugs (after discounts and rebates, for example) will depend on negotiations with payers.
Whether the increased competition achieves Dr. Gottlieb’s stated goal of bringing down drug prices remains to be seen. But, whatever the result, the Lynparza result signals a willingness on the part of FDA to think and act in new ways. I suspect this decision will motivate companies to seek broader approvals, which may lead to greater competition and, ultimately, more choices and lower prices for patients.