Loxo Oncology Seeks FDA Approval After Breakthrough Drug Larotrectinib Helped Almost Everyone Who Took It

June 5, 2017
By Alex Keown, BioSpace.com Breaking News Staff

STAMFORD, Conn. – Shares of Loxo Oncology have rocketed up more than 48 percent this morning after the company unveiled data from three trials that showed treatment with larotrectinib helped nearly three-quarters of patients battling a variety of cancers.

Loxo revealed the data at the American Society of Clinical Oncology meeting in Chicago this weekend. According to the company, 76 percent of patients who have tumors that harbor tropomyosin receptor kinase (TRK) fusions achieved an objective response rate (ORR). The data presented at ASCO includes adult and pediatric patients with RECIST-evaluable TRK fusion cancers.

David Hyman, chief investigator and chief of the early drug development service at Memorial Sloan Kettering Cancer Center Center, said larotrectinib delivered consistent and durable responses in TRK fusion patients across all ages, regardless of tumor context, and does so with few side effects.” With the high efficacy rate and the lack of side effects, Hyman said the Loxo drug “fulfills the promise of precision medicine.”

Hyman told Reuters that about 5,000 patients in the United States are diagnosed annually with the TRK-positive defect. He noted those numbers could climb if comprehensive genetic testing becomes more common.

“It is now incumbent upon the clinical oncology and pathology communities to examine our testing paradigms, so that TRK fusions and other actionable biomarkers become part of the standard patient workup,” Hyman said in a statement.

Larotrectinib, an orally-taken selective TRK inhibitor, was designed to address solvent front and other acquired resistance mutations to potentially induce new responses in TRK fusion dependent cancers with acquired resistance mutations. Loxo said data shows the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body.

The three Loxo trials studied followed 50 TRK fusion-positive patients with multiple cancer types, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor (GIST), infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. Overall results show that 76 percent of patients with confirmed response data showed an overall response rate, with 12 percent showing a complete response. When additional patients who were more recently enrolled in the larotrectinib trials were factored in, the overall response rate ticked up a bit to 78 percent with 13 percent showing a complete response.

ORR was generally consistent across tumor types, TRK gene fusions, and various diagnostic tests, Loxo said. In the pediatric setting, larotrectinib showed promising activity in the pre-surgical management of patients with infantile fibrosarcoma, with three patients treated to best response, which allowed for subsequent referral to surgery with curative intent, the company added.

The company said the data presented at ASCO will serve as the basis for a New Drug Application the company will file with the U.S. Food and Drug Administration by the end of 2017 or the beginning of 2018. The company said the primary analysis for the NDA will rely on independent review, which will be conducted later this year. Larotrectinib received Breakthrough Therapy Designation from the FDA in July 2016.

The majority of trial patients who responded to the treatment, 93 percent, remain on larotrectinib or received surgery with curative intent. Last month, the FDA approved Loxo’s Investigational New Drug application for LOXO-195. LOXO-195 is a TRK inhibitor. It was developed to treat patients with TRK fusion cancers who become resistant while receiving another TRK inhibitor, such as larotrectinib.

Shares of Loxo Oncology are trading at $70.91 as of 10:06 a.m., significantly higher than Friday’s closing of $49.73.