[Updated, 5/11/2020, 10:03 a.m. See below.] Eli Lilly received accelerated FDA approval Friday for a drug that treats advanced cancers carrying a certain genetic signature. It’s the latest targeted cancer therapy to pass the regulatory bar and the first that addresses tumors characterized by aberrations in one particular gene.
The gene in question, RET, produces a protein involved in cell signaling. Approval of the Lilly (NYSE: LLY) drug, selpercatinib (Retevmo), covers non-small cell lung cancer (NSCLC), thyroid cancer, and the rarer medullary thyroid cancer, which originates from different cells than other thyroid cancers. Those cancer cells treated by the Lilly drug must have a genetic alteration to RET—either a mutation or a fusion to another gene—that sparks the overactive cell signalling leading to tumor growth.
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Selpercatinib, a capsule taken twice daily, is designed to block an enzyme that is key to this tumor growth. But before a patient receives the Lilly drug, the RET gene alteration must be confirmed by a lab test. As of now, there is no FDA-approved companion diagnostic for detecting RET fusions or mutations.
The FDA decision was based on the results of a Phase 1/2 clinical trial that enrolled lung and thyroid cancer patients, both those who had previously been treated for their disease and those who had not. The study’s goals were to measure overall response to treatment and the duration of that response.
In NSCLC, the study enrolled patients that had RET fusion-driven cancers. In 105 patients previously treated with chemotherapy, the overall response to the Lilly drug was 64 percent, the FDA said. For 81 percent of those responders, the drug’s effect lasted at least six months. The clinical trial also tested the drug in 39 NSCLC patients who had never been treated previously. In that group, the overall response rate was 84 percent. In 58 percent of those responders, the drug’s effect lasted at least six months.
The medullary thyroid cancer portion of the study enrolled patients age 12 and older whose disease had RET mutations. The FDA said the overall response rate in 55 previously treated patients was 69 percent. In responders, 76 percent saw the drug’s effect last at least six months. In 88 previously untreated patients, the overall response rate was 73 percent; the six month mark was met in 61 percent of those responders.
In thyroid cancer, the study enrolled patients age 12 and older whose disease was positive for RET fusions. The overall response rate for the 19 patients, all of whom were previously treated, was 79 percent. The response lasted at least six months in 87 percent of responders. In eight patients who had not received previously treatment other than radioactive iodine, all of them responded to the Lilly drug; that response lasted at least six months in 75 percent of them.
The FDA said that the most common side effects included elevated liver enzymes, an increase in blood sugar, a drop in blood pressure, dry mouth, diarrhea, and an increase in the muscle waste product creatinine. More serious side effects included liver damage or injury. The drug’s label notes that serious liver problems occurred in 2.6 percent of patients and cautions that liver enzymes should be monitored. Treatment should be reduced or stopped depending on the severity of any liver problems. Hypertension occurred in 35 percent of patients and the drug should not be used in patients with uncontrolled high blood pressure, according to the label.
An FDA decision for selpercatinib was not expected until the third quarter of this year. The approval was made on an accelerated basis under a pathway that the regulator reserves for drugs that address serious or life-threatening conditions. But such approvals require companies to provide additional clinical data to confirm the drug’s benefit to patients. Lilly says it is currently enrolling two confirmatory Phase 3 studies.
Selpercatinib’s approval is the second accelerated decision this week in NSCLC. Novartis (NYSE: NVS) won a regulatory nod Wednesday for capmatinib (Tabrecta), a drug that targets cancers characterized by mutations to the MET gene.
Approval of the Lilly drug marks a payoff for the company, which added the therapy to its pipeline last year via an $8 billion acquisition of Loxo Oncology. The deal was a bet on Loxo’s targeted cancer approach, coming less than two months after the company secured FDA approval for larotrectinib (Vitrakvi), a drug targeting cancers that have fusions of the NTRK gene. That decision covered solid tumors as long as they have the NTRK fusion. At the time, it was the second FDA approval for a cancer therapy targeting a particular genetic signature regardless of where in the body tumors are found.
In getting the regulatory nod for selpercatinib, Lilly beats Blueprint Medicines (NASDAQ: BPMC) to the market. That Cambridge, MA-based biotech has also developed a RET inhibitor, pralsetinib. Last month, the company completed a a rolling submission to the FDA seeking approval for the drug in RET fusion-positive NSCLC. Based on preliminary Phase 1/2 data in medullary thyroid cancer, Blueprint plans to an additional submission in that indication this quarter. [Updated to clarify the regulatory status of pralsetinib.]
Lilly says it expects to make selpercatinib available through specialty pharmacies within the next week.
Photo by Eli Lilly.