FDA Approves Blueprint Cancer Drug Targeting RET Genetic Signatures

[Updated, 9/8/2020. See below.] A Blueprint Medicines drug for cancers that carry a certain genetic signature has received FDA approval, making it the latest targeted therapy to pass the regulatory bar this year.

The late Friday decision for pralsetinib (Gavreto) covers non-small cell lung cancer (NSCLC). The drug was designed to address cancers characterized by fusions or mutations of the RET gene, which produces a protein involved in cell signaling. Genetic abnormalities to the gene drive many types of cancer, including NSCLC. To be eligible for treatment, the RET alterations must first be detected by a genetic test. The drug from Cambridge, MA-based Blueprint (NASDAQ: [[ticker:BPMC]]), a once-daily pill, is designed to block RET alterations.

In a clinical trial testing pralsetinib in 87 patients previously treated with chemotherapy, the overall response rate was 57 percent. Of those responders, 5.7 percent of them showed a complete response, meaning all signs of the cancer were gone. The duration of the response could not be estimated. In a group of 27 patients who were not eligible for chemotherapy, the overall response rate to treatment was 70 percent; the complete response rate was 11 percent. The median duration of the response was nine months.

Serious adverse reactions to the drug were reported for 45 percent of patients. The most common of these problems were pneumonia, inflammation of lung tissue, sepsis, urinary tract infection, and fever. The drug’s label includes warnings of potential lung and liver problems, hypertension, bleeding, and impaired wound healing.

Pralsetinib’s approval comes well ahead of the November target date for a decision. The accelerated approval pathway is reserved for therapies that address serious or life-threatening conditions. But these speedier approvals based on a thinner body of evidence than is typically required mean that a company needs to conduct additional clinical testing to confirm its drug’s benefit to patients.

The regulatory decision for the Blueprint drug comes four months after the FDA gave the green light to capmatinib (Tabrecta), a targeted cancer therapy from Novartis (NYSE: [[ticker:NVS]]) that addresses NSCLC characterized by mutations to a different gene, MET. Days later, the FDA approved the first RET-targeting medicine, selpercatinib (Retevmo), a twice-daily capsule from Eli Lilly (NYSE: [[ticker:LLY]]). In addition to NSCLC, the Lilly drug was approved for treating thyroid cancer and medullary thyroid cancer, which is caused by a different type of cells than other thyroid cancers. Blueprint is also seeking approval for its drug in thyroid cancer and medullary thyroid cancer.

[Paragraph updated with details from conference call.] Blueprint will bring pralsetinib to the market in partnership with Roche subsidiary Genentech. In July, Roche agreed to pay $675 million up front for global right rights to the drug, except for China. Under the deal, Blueprint and Genentech will collaborate on commercializing the drug in the US. Roche also made a $100 million equity investment in Blueprint, and the biotech could earn up to $927 million more in milestone payments. With the approval, Blueprint earned a $40 million milestone payment, CEO Jeff Albers said on a conference call Tuesday. The company has set a $19,250 price for a 30-day supply of the drug, which is below the $20,600 mark set by Lilly for a 30-day supply of its drug. Albers said that patients will benefit from more than one choice.

“Ultimately, these are really sick patients and having options is a good thing,” he said. “I’ve said it a hundred times. If, for whatever reason, a patient doesn’t tolerate one of our medicines, I hope there’s another therapy they can get.”

Pralsetinib is now Blueprint’s second product to win the FDA’s OK this year. The first, avapritinib (Ayvakit), was approved in January for treating gastrointestinal stromal tumors characterized by a particular genetic mutation.

Blueprint says pralsetinib should be available in the US within a week.

Image: iStock/Igor Kutyaev