- The Food and Drug Administration approved a new cancer drug on Monday for tumors harboring a rare genetic alteration, marking the second time the regulator has permitted a therapy to be used based solely on the DNA makeup of a patient's cancer rather than where it originated in the body.
- Developed by Loxo Oncology, Vitrakvi is OK'd for patients with advanced solid tumors that test positive for an uncommon melding of a gene called NTRK with other genes. The resulting fusion produces an altered protein that can drive tumor growth.
- Only a few thousand patients in the U.S. are estimated to be affected by TRK fusion cancer each year. Vitrakvi's approval, though, carries broader significance for oncology research, signaling the growing use of biomarkers to guide therapy. The drug won't come cheap, with a list price that could reach as high as $32,800 per month.
Approval of Vitrakvi (larotrectinib) was largely expected, after clinical results showed an impressive 75% of patients with TRK fusion cancers responded to treatment. Notably, patients with a wide range of solid tumors experienced a benefit from Vitrakvi, underscoring the drug's utility as a so-called tissue-agnostic therapy.
"This type of drug development program, which enrolled patients with different tumors but a common gene mutation, wouldn't have been possible a decade ago because we knew a lot less about such cancer mutations," said FDA Commissioner Scott Gottlieb, in a statement from the agency on the approval.
The nod for Vitrakvi follows a landmark approval last May for Merck & Co.'s Keytruda (pembrolizumab) in patients with solid tumors whose cancer is judged to be microsatellite instability-high or mismatch repair deficient.
Until now, treating cancer has been rooted in where the disease originated in the body. The result has been a taxonomy defined by organs: lung cancer or colon cancer, for example. Targeted therapies have narrowed that lens to specific mutations within each tumor type — such as EGFR or ALK in lung cancer — but treatment has still been based on the site of origin.
Keytruda and Vitrakvi, by contrast, are seen as the leading edge of an effort to push science's improved understanding of cancer genetics one step further.
While broad in the genetic sense, Vitrakvi's approval is limited. Only patients with advanced solid tumors that test positive for the mutation without any known resistance mechanism, and who have either progressed following other treatment or have no other alternatives, are approved to receive the drug.
Loxo and its partner Bayer will also face significant challenges in achieving commercial success. NTRK fusions are extremely rare, making the companies' first task finding patients who are eligible for the drug.
Since patients need to be specifically screened for NTRK fusion, testing could present a bottleneck — particularly outside of major academic and clinical centers.
"If you get out into the rural community setting, testing just isn't being done for even some of the established genetic mutations today," said Jillian Scaife, a principal at Trinity Partners, in an interview with BioPharma Dive.
Scaife also noted payers will need to be onboard with covering the testing in the first place, too.
"Are payers really going to pay for expensive NGS testing for every single lung cancer patient to identify that 1% or 5% of patients that have this very rare genetic mutation?" she said, referring to next-generation sequencing.
Bayer estimates that TRK fusion cancer affects between 2,500 and 3,000 new patients each year in the U.S., but noted in a statement to BioPharma Dive that most currently go undiagnosed.
That small patient population underpins a list price that puts Vitrakvi in the top ranks of costly cancer therapies. Bayer, which co-promotes in the U.S. with Loxo, set the drug's list price for a month's supply of 100 mg capsules at $32,800 — putting the annual cost close to $400,000.
A liquid oral formulation of the drug for certain pediatric patients, based on body surface area, will cost $11,000 per month, however.
Bayer says it will refund the cost of the drug for eligible patients who "do not experience clinical benefit within 90 days of treatment initiation," but didn't define what constitutes a clinical benefit.
In clinical testing, responses to Vitrakvi lasted at least six months for about three quarters of responding patients, and at least 12 months in nearly 40% of responding patients.
Results submitted by Loxo for approval included efficacy data on 55 patients as well as safety results from a broader group of 176 patients. The drug's label warns of the risk of neurotoxicity, hepatotoxicity and embryo-fetal toxicity.