8 September 2020 - - The US Food and Drug Administration has approved Gavreto (pralsetinib) for the treatment of adults with metastatic rearranged during transfection fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test, US-based biotechnology company Genentech said.

This indication was approved under the FDA's accelerated approval program based on data from the Phase I/II ARROW study.

Genentech is a member of Switzerland's Roche Group (SIX: RO) (OTCQX: RHHBY).

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations.

RET-activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and medullary thyroid cancer, and treatment options that selectively target these genetic alterations are limited. In NSCLC, RET fusions represent approximately 1-2% of patients.

Biomarker testing for these fusions is the most effective way to identify people who are eligible for treatment with Gavreto.

The approval is based on the results from the Phase I/II ARROW study, in which Gavreto produced durable clinical responses in people with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement.

Gavreto demonstrated an overall response rate of 57% (95% CI: 46%, 68%) and complete response rate of 5.7% in the 87 people with NSCLC previously treated with platinum-based chemotherapy, and the median duration of response was not reached (95% CI: 15.2 months, not reached).

In the 27 people with treatment-naïve NSCLC, the ORR was 70% (95% CI: 50%, 86%) with an 11% CR rate. The most common adverse reactions were fatigue, constipation, musculoskeletal pain and increased blood pressure (hypertension).

Gavreto is now the sixth FDA-approved medicine in Genentech's portfolio of treatments for lung cancer.

The FDA granted Breakthrough Therapy Designation to Gavreto for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

The FDA has also granted Priority Review to Gavreto for the treatment of people with advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer, and is expected to make a decision on approval by February 28, 2021.

This New Drug Application was accepted for review under the FDA's Real-Time Oncology Review pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

For those who qualify, Blueprint Medicines will offer patient assistance programs for people prescribed Gavreto by their doctor through YourBlueprint.

ARROW (NCT03037385) is a Phase I/II, open-label, first-in-human study designed to evaluate the safety, tolerability and efficacy of Gavreto, administered orally in people with rearranged during transfection fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer and other RET-altered solid tumors.

The trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in people treated with 400 mg of Gavreto, once-daily.

ARROW is being conducted at multiple sites across the United States, European Union and Asia.

According to the American Cancer Society, it is estimated that more than 228,000 Americans will be diagnosed with lung cancer in 2020, and NSCLC accounts for 80-85% of all lung cancers.

It is estimated that approximately 85% of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

In NSCLC, RET fusions represent approximately 1-2% of patients.

Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations, regardless of the tissue of origin.

Preclinical data have shown that Gavreto inhibits primary RET fusions and mutations that cause cancer in subsets of patients, as well as secondary RET mutations predicted to drive resistance to treatment.

Blueprint Medicines and Genentech are also co-developing Gavreto for the treatment of patients with various types of RET-altered thyroid cancers and other solid tumors.

Gavreto (pralsetinib) is indicated for the treatment of adult patients with metastatic rearranged during transfection fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.