Twenty four gene fusions in one drug approval

A first-in-class inhibitor of tropomyosin receptor kinase (TRK) won accelerated approval on 26 November from the Food and Drug Administration (FDA) for treating tumors bearing fusions in one of the three neurotrophic receptor tyrosine kinase genes that encode TRK family proteins, regardless of where the cancer originated in the body.

The FDA nod for Vitrakvi (larotrectinib) from Loxo Oncology and its development partner Bayer represents the second tissue-agnostic approval. The first went, in May 2017, to Merck’s Keytruda (pembrolizumab)—an already marketed immunotherapy drug—for patients with tumors exhibiting particular indicators of genomic instability (Nat. Biotechnol. 35, 297–298, 2017). But Vitrakvi is the first to receive a tissue-agnostic approval either for a gene-targeted therapy or for a new drug candidate in its initial clinical indication.

Earlier data met with great interest among the cancer community (Nat. Biotechnol. 35, 694–695, 2018). In the three trials leading up to the approval, researchers evaluated Vitrakvi in 122 children, adolescents or adults who collectively had 24 different types of TRK fusion–positive tumors. The latest results—presented at the European Society for Medical Oncology 2018 Congress in Munich, Germany, on 21 October—showed that the drug was safe and efficacious regardless of age, tumor type or the nature of TRK fusion. Overall, 63% of participants exhibited partial responses and another 17% experienced complete tumor disappearance.

This level of efficacy is unparalleled, says trial investigator Noah Federman, a pediatric hematologist-oncologist at the University of California, Los Angeles’s Jonsson Comprehensive Cancer Center. “This is a big deal in the pediatric and adult oncology world,” he says. “As trite as the word ‘game-changer’ is in oncology, this is one of the few times this descriptor is warranted in our field.”

Nichol Miller was the first patient in the world to receive Vitrakvi—in her case, for a metastatic sarcoma originating from the hip flexor muscle. She has now been on the drug with a durable response for close to 4 years and counting. “It’s absolutely incredible,” says Miller, a 45-year-old rideshare driver and mother of three from Beaverton, Oregon. Before the treatment, “I was in a wheelchair, on five liters of oxygen an hour, barely coherent and I was dying,” she says. “Six weeks later, I went horseback riding. The tumors just melted away.”

Now that Vitrakvi has won approval, Miller says it “warms my heart” to know that other cancer patients with TRK fusions—which are found in less than 1% of all solid tumors—will now have access to the drug. However, it won’t come cheap. According to Bayer, the wholesale monthly cost will be $32,800 for adults and at least $11,000 for children, although the company pledged to offer payment assistance for patients with poor insurance coverage and a money-back guarantee if the drug doesn’t provide clinical benefit in the first three months.