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Lilly's Loxo buyout bears fruit as FDA clears cancer drug Retevmo.

The Food and Drug Administration on Friday approved a new drug for three types of cancer driven to grow by a certain abnormal gene, clearing Eli Lilly's Retevmo several months ahead of schedule.

Retevmo is the first approved therapy for lung and thyroid tumors with alterations in that gene, called RET, and adds to a lengthening list of genetically targeted medicines that have become standard treatment for some cancers.​

Previously known as selpercatinib, Retevmo was the chief draw in Lilly's $8 billion acquisition of Loxo Oncology early last year. The Indianapolis-based pharma hopes the addition of Loxo can reinvigorate its cancer drug business, which has lagged industry leaders like Merck & Co., Roche and Bristol Myers Squibb. Loxo had already won approval of a targeted cancer therapy prior to the deal and had several others in development, among them Retevmo.

Approval of Retevmo is therefore an important milestone for Lilly, as well as a test case for major changes the drugmaker made in December to how it organized its oncology division. Loxo executives, including the biotech's former CEO Josh Bilenker, were appointed leaders of a new group that merged Lilly's laboratories with Loxo's.

Development of Retevmo took just three years from when the first clinical trials began, reflecting the speed at which genetically targeted cancer drugs can be advanced. By matching treatments to patients most likely to benefit, drugmakers have designed smaller studies that the FDA has been willing to accept as sufficient evidence for faster-than-normal approvals. Drugmakers then have to run additional tests to confirm the results. Lilly, for instance, has two such confirmatory studies underway for Retevmo.

Approximately 2% of lung cancers harbor RET alterations, according to Lilly, as well as some 10% to 20% of thyroid cancers. Many fewer people are diagnosed with thyroid cancer than lung cancer in the U.S., meaning the number of patients who could benefit from Retevmo is small, likely around several thousand each year.

The FDA's approval clears Retevmo for use only in those patients whose lung or thyroid cancer has either spread or stopped responding to initial treatment. Confirmation of a RET alteration, done through biomarker testing, is required. There is no FDA-approved test for RET abnormalities, however, meaning a diagnosis must be made by local laboratory tests, such as those commonly available at major cancer centers.

Most patients with RET-driven lung cancer are treated first with either chemotherapy or chemotherapy combined with immunotherapy. If their tumors continue to grow, however, second-line options are limited and typically only work 10% to 15% of the time, according to John Heymach, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center.

In an email, Heymach said Retevmo would "clearly fill a niche similar to tyrosine kinase inhibitors for patients with ALK-positive or EGFR-mutant tumors," referring to two more common mutations in lung cancer.

Such drugs, like Roche's Alecensa and AstraZeneca's Tagrisso, have become go-to treatment options when those mutations are present, even as immunotherapies like Merck & Co.'s Keytruda are now more widely used.

Retevmo was tested in a single-arm study of 702 patients with RET-driven cancers. The drug, which is taken orally, helped to shrink tumors in 33 of 39 previously untreated lung cancer patients, and in 67 of 105 patients whose cancer had continued to grow after initial therapy.

Response rates ranged between 69% and 100% across several different groups of thyroid cancer patients tested in the trial.

Data on how long patients went without their cancers progressing is still incomplete, but initial results from Lilly suggest responses last at least six months. Among the 105 previously treated lung cancer patients, the median duration of response was nearly a year and a half. It's unclear whether those lengthy responses are helping extend patients' lives, however.

Retevmo can cause liver problems, as well as high blood pressure, heart rhythm abnormalities and bleeding.

The FDA's willingness to speed cancer drugs to market with no, or only limited information, on their survival benefit has become a point of some controversy. But the agency, as well as some cancer doctors, argue preliminary evidence showing patients respond to a drug can still make a strong case for benefit, particularly when genetic testing can match patients to treatment.

Gilberto Lopes, an oncologist at the Sylvester Comprehensive Cancer Center at the University of Miami, called overall response rate and progression-free survival "acceptable surrogate endpoints for the approval of targeted therapies in lung cancer."

"Historically ... we have never seen median survivals in excess of two years as commonly seen in recent trials of targeted agents in metastatic non-small cell lung cancer," Lopes wrote in an email to BioPharma Dive, referring in general to newer cancer therapies.

While cancer drugs like Retevmo offer a more specific approach than systemic treatment like chemotherapy, they are expensive. Lilly set the list price of Retevmo at $20,600 per 30 days of therapy, a sum in between the cost of similar, genetically targeted cancer drugs Vitrakvi and Rozlytrek.

Vitrakvi, which was originally developed by Loxo and is now sold by Bayer, costs $32,800 for roughly a month's worth of treatment, which Roche sells Rozlytrek for $17,050 a month.

Author: Ned Pagliarulo

Published: May 9, 2020

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