3 December 2020 - - The US Food and Drug Administration has approved Gavreto (pralsetinib) for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic rearranged during transfection -mutant medullary thyroid cancer who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate), US-based biotechnology company Genentech said.

Genentech is a member of the Roche Group (SIX: RO) (OTCQX: RHHBY).

These indications were approved under the FDA's accelerated approval program based on data from the Phase I/II ARROW study. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Approximately 10-20% of people with papillary thyroid cancer (the most common type of thyroid cancer) have RET fusion-positive tumors, and roughly 90% of people with advanced MTC (a rare form of thyroid cancer) carry RET mutations.

Biomarker testing for RET fusions and mutations can help identify people who are eligible for treatment with Gavreto.

The approvals are based on results from the Phase I/II ARROW study, which demonstrated durable clinical activity in people with or without prior therapy and regardless of RET alteration genotypes.

Treatment with Gavreto led to an overall response rate of 60% (95% CI: 46%, 73%) in 55 people with RET-mutant metastatic MTC previously treated with cabozantinib and/or vandetanib, and the median duration of response was not reached (95% CI: 15.1 months, not estimable).

In 29 people with RET-mutant advanced MTC who were cabozantinib and vandetanib treatment-naïve, the ORR was 66% (95% CI: 46%, 82%), and the median DoR was not reached (95% CI: not estimable, not estimable).

In nine people with RET fusion-positive metastatic thyroid cancer, Gavreto demonstrated an ORR of 89% (95% CI: 52%, 100%), and the median DoR was not reached (95% CI: not estimable, not estimable).

In ARROW trial patients across RET-altered tumor types, the most common adverse reactions were constipation, increased blood pressure (hypertension), fatigue, musculoskeletal pain and diarrhea.

The FDA reviewed and approved the application under its 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.

In September, the FDA also granted accelerated approval to Gavreto for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.

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

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

Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations. Gavreto is jointly commercialized by Genentech and Blueprint Medicines in the United States.

For those who qualify, Blueprint Medicines offers 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 cancers 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.

RET gene alterations, such as fusions and mutations, are key disease drivers in many types of cancer, including NSCLC and several types of thyroid cancers.

Approximately 10-20% of people with papillary thyroid cancer (the most common type of thyroid cancer) have RET fusion-positive tumors, and roughly 90% of people with advanced MTC (a rare form of thyroid cancer) carry RET mutations.

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

Oncogenic RET fusions also are observed at low frequencies in cholangiocarcinoma, colorectal, neuroendocrine, ovarian, pancreatic and thymus cancers.

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 co-developing Gavreto for the treatment of patients with various types of RET-altered cancers.