SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, Inc., a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) 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 (RET)-mutant medullary thyroid cancer (MTC) 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). 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.

“We are proud to partner with Blueprint Medicines to bring this important new option to people with certain types of RET-altered thyroid cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Gavreto is now approved across multiple RET-altered tumor types, underscoring our commitment to advancing personalized healthcare with treatments that target the underlying biology of each person’s cancer.”

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 (ORR) 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 (DoR) 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 (≥25%) were constipation, increased blood pressure (hypertension), fatigue, musculoskeletal pain and diarrhea.

The FDA reviewed and approved the application under its Real-Time Oncology Review (RTOR) 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^™. Please visit www.yourblueprint.com or contact 1-888-BLUPRNT for more information.

About the ARROW study

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 (RET) fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer (MTC), 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.

About RET-altered cancers

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.

About Gavreto

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.

Gavreto™ U.S. Indications

Gavreto^™ (pralsetinib) is indicated for the treatment of:

• Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.
• Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy.
• Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

Interstitial Lung Disease (ILD)/Pneumonitis occurred in 10% of patients who received Gavreto, including 2.7% with Grade 3/4, and 0.5% with fatal reactions. Monitor for pulmonary symptoms indicative of interstitial lung disease (ILD)/pneumonitis. Withhold Gavreto and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue Gavreto based on severity of confirmed ILD.

Hypertension occurred in 29% of patients, including Grade 3 hypertension in 14% of patients. Overall, 7% had their dose interrupted and 3.2% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Gavreto in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Gavreto. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Gavreto based on the severity.

Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.1% of patients treated with Gavreto. Increased aspartate aminotransferase (AST) occurred in 69% of patients, including Grade 3/4 in 5% and increased alanine aminotransferase (ALT) occurred in 46% of patients, including Grade 3/4 in 6%. The median time to first onset for increased AST was 15 days (range: 5 days to 1.5 years) and increased ALT was 22 days (range: 7 days to 1.7 years). Monitor AST and ALT prior to initiating Gavreto, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue Gavreto based on severity.

Grade ≥ 3 hemorrhagic events occurred in 2.5% of patients treated with Gavreto including one patient with a fatal hemorrhagic event. Permanently discontinue Gavreto in patients with severe or life-threatening hemorrhage.

Tumor Lysis Syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving Gavreto. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Gavreto has the potential to adversely affect wound healing. Withhold Gavreto for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Gavreto after resolution of wound healing complications has not been established.

Based on findings from animal studies and its mechanism of action, Gavreto can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with Gavreto and for 2 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Gavreto and for 1 week after the final dose. Advise women not to breastfeed during treatment with Gavreto and for 1 week after the final dose.

Common adverse reactions (≥25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea. Common Grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased AST, increased ALT, decreased platelets and increased alkaline phosphatase.

Avoid coadministration of Gavreto with strong CYP3A inhibitors or combined P-gp and strong CYP3A inhibitors. If coadministration cannot be avoided, reduce the Gavreto dose. Avoid coadministration of Gavreto with strong CYP3A inducers. If coadministration cannot be avoided, increase the Gavreto dose.

Please click here to see the full Prescribing Information for Gavreto.

Blueprint Medicines, Gavreto, YourBlueprint and associated logos are trademarks of Blueprint Medicines Corporation.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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