FDA Approves Vitrakvi (larotrectinib), First Tumor-Agnostic TRK Inhibitor with 75% Overall Response Rate in NTRK Fusion Cancers

VCBeat (WeChat: vcbeat) has learned that on November 26, 2018, U.S. local time, Vitrakvi (larotrectinib), a novel targeted anticancer drug jointly launched by Bayer and Loxo Oncology (hereinafter referred to as “Loxo”), received marketing approval from the U.S. Food and Drug Administration (FDA). This marks the FDA’s first approval of a TRK inhibitor and the first anticancer drug indicated irrespective of tumor type, for adult and pediatric patients with solid tumors harboring NTRK gene fusions. Clinical results demonstrated that Vitrakvi achieved an overall response rate of up to 75% across various cancers driven by NTRK gene fusions.

Image source: Loxo official website

Vitrakvi is an oral TRK inhibitor indicated for adult and pediatric patients with locally advanced or metastatic solid tumors harboring NTRK gene fusions, provided that no known resistance mutations have developed. Unlike other anticancer agents, Vitrakvi does not target cancer phenotypes but rather addresses the underlying driver of the disease—NTRK gene fusions. Cancers driven by this mechanism are collectively referred to as TRK fusion cancers.

NTRK gene fusions occur when the NTRK gene in the human body fuses with an unrelated gene, resulting in the production of a TRK protein. This protein can drive the growth and survival of solid tumors in various parts of the body. TRK fusion cancers are not restricted by cancer type or anatomical location (tissue, cell type, or site); the presence of an NTRK gene fusion is sufficient to cause TRK fusion cancer. Vitrakvi works by inhibiting these TRK proteins to treat patients with advanced-stage cancer. Although NTRK gene fusions are relatively rare, they occur across a wide range of cancer types.

Cancer types known to be driven by NTRK gene fusions include: lung cancer, thyroid cancer, gastric cancer (colon cancer, cholangiocarcinoma, pancreatic cancer, and appendiceal cancer), sarcoma, colon cancer, central nervous system cancers (glioma, glioblastoma), salivary gland cancers (secretory carcinoma with mammary analogue features), and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).

It should be noted that the drivers of cancer are diverse, and patients can undergo genetic testing to determine whether they have TRK fusion cancer.

According to data published by the FDA, clinical trial results for patients aged 4 months to 76 years with TRK fusion cancers showed that Vitrakvi achieved an objective response rate (ORR) of 75% (N = 55) (95% CI, 61%, 85%), a partial response (PR) rate of 53%, and a complete response (CR) rate of 22%. The trial results also indicated that, following treatment with Vitrakvi, 73% of patients had a duration of response of less than 6 months, 63% had a duration of response of less than 9 months, and 39% had a duration of response of less than 12 months.

Meanwhile, Vitrakvi is also associated with potential side effects, such as neurotoxicity, hepatotoxicity, and fetal toxicity. Approximately 20% of patients in clinical trials (regardless of attribution) exhibited varying degrees of anemia, fatigue, nausea, dizziness, cough, vomiting, constipation, and diarrhea.

The U.S. FDA granted Vitrakvi Breakthrough Therapy Designation, Rare Pediatric Disease Designation, and Orphan Drug Designation, and accorded it Priority Review.

Bayer and Loxo have engaged in an exclusive global collaboration since November 2017 for the development and commercialization of Vitrakvi and another drug, Loxo-195. Loxo-195 is also an NTRK inhibitor, designed to treat patients who have developed resistance to Vitrakvi. Following FDA approval, Vitrakvi will immediately enter the U.S. market, with both companies jointly promoting the drug. In August this year, Bayer also submitted a Marketing Authorization Application (MAA) for Vitrakvi to the European Union; the review process is currently ongoing.

Meanwhile, to ensure that patients in the United States have easier access to this medication, Bayer has launched the Vitrakvi Commitment Program. Under this program, if eligible patients do not achieve clinical benefit within 90 days of initiating treatment, Bayer will refund the cost of Vitrakvi therapy to payers, patients, and third-party organizations. Eligibility criteria include three aspects: 1) confirmed positive for NTRK gene fusion; 2) obtaining Vitrakvi through an in-network specialty pharmacy; and 3) failure to achieve clinical benefit within 90 days of starting treatment.

Bayer, founded in 1863 and headquartered in North Rhine-Westphalia, Germany, is a multinational pharmaceutical company with unique core competencies in the fields of healthcare and agricultural life sciences. In fiscal year 2017, the Group employed approximately 99,800 people and achieved sales of €35 billion.

Loxo, founded in 2013 and headquartered in New York, USA, is a biopharmaceutical company focused on developing targeted therapies for patients with genetically defined cancers.