Genentech Provides Update on Gavreto U.S. Indication for Advanced or Metastatic Medullary Thyroid Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the company, in partnership with Blueprint Medicines, is voluntarily withdrawing the U.S. indication of 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. 

Gavreto was granted approval for this indication under the U.S. Food and Drug Administration’s (FDA’s) Accelerated Approval Program in December 2020. Full approval was contingent upon demonstration of clinical benefit in the confirmatory Phase III randomized AcceleRET MTC study [NCT04760288] investigating Gavreto versus the standard of care in RET-mutant MTC. Genentech and Blueprint Medicines made the decision to voluntarily withdraw the U.S. RET-mutant MTC indication following consultation with the FDA, as the confirmatory AcceleRET MTC study could not be activated to fulfill the postmarketing requirement. 

This decision is not based on the efficacy or safety of Gavreto and does not affect the other approved Gavreto indications in the U.S. for RET fusion-positive thyroid cancer and non-small cell lung cancer. Genentech with Blueprint Medicines will work with the FDA over the coming weeks to complete the withdrawal process and notify healthcare professionals in the U.S. about this withdrawal. Patients in the U.S. being treated with Gavreto for advanced or metastatic RET-mutant MTC who require systemic therapy should discuss their care options with their healthcare provider.

About Gavreto® (pralsetinib)

Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations, regardless of the tissue 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 have been co-developing Gavreto for the treatment of patients with various types of RET-altered cancers. Earlier this year, Genentech discontinued its collaboration agreement with Blueprint Medicines for Gavreto. Under the terms of the agreement, the termination will be effective 12 months from the notification date of February 22, 2023. 

WHAT IS GAVRETO® (pralsetinib)?

GAVRETO® (pralsetinib) is a prescription medicine used to treat certain cancers caused by abnormal rearranged during transfection (RET) genes in:

  • adults with non-small cell lung cancer (NSCLC) that has spread 
  • adults and children 12 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread who require a medicine by mouth or injection (systemic therapy) 
  • adults and children 12 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy) and who have received radioactive iodine and it did not work or is no longer working

Healthcare providers will perform a test to make sure that GAVRETO is right for each patient.

It is not known if GAVRETO is safe and effective in children younger than 12 years of age.

GAVRETO was approved based on the percentage of patients whose tumor size shrank or disappeared after treatment and how long that response lasted. There are ongoing studies to confirm the benefit of GAVRETO.

IMPORTANT SAFETY INFORMATION

GAVRETO® (pralsetinib) may cause serious side effects, including

Lung Problems: GAVRETO may cause severe or life-threatening inflammation of the lungs during treatment, that can lead to death. Patients should tell their healthcare provider right away if they have any new or worsening symptoms, including shortness of breath, cough, or fever. 

High blood pressure (hypertension): High blood pressure is common with GAVRETO and may sometimes be severe. Patients should check their blood pressure regularly during treatment with GAVRETO. Patients should tell their healthcare provider if they have increased blood pressure readings or get any symptoms of high blood pressure, including confusion, dizziness, headaches, chest pain or shortness of breath. 

Liver problems: Liver problems (increased liver function blood test results) can happen during treatment with GAVRETO and may sometimes be serious. Healthcare providers will do blood tests before and during treatment with GAVRETO to check for liver problems. Patients should tell their healthcare provider right away if they get any signs or symptoms of liver problem during treatment, including yellowing of the skin or the white part of the eyes (jaundice), loss of appetite, nausea or vomiting, dark “tea-colored” urine, pain on the upper right side of the stomach area, sleepiness, bleeding or bruising. 

Bleeding problems: GAVRETO can cause bleeding which can be serious and cause death. Patients should tell their healthcare provider if they have any signs or symptoms of bleeding during treatment, including vomiting blood or if vomit looks like coffee-grounds, unusual vaginal bleeding, nose bleeds that happen often, pink or brown urine, drowsiness or difficulty being awakened, red or black (looks like tar) stools, confusion, coughing up blood or blood clots, headache, unusual bleeding or bruising of the skin, change in speech, or menstrual bleeding that is heavier than normal. 

Tumor lysis syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, an abnormal heartbeat, and may sometimes lead to hospitalization. Healthcare providers may do blood tests to check for TLS. Patients should stay well hydrated during treatment with GAVRETO. Patients should call their healthcare provider or get emergency medical help right away if they develop any of these symptoms during treatment with GAVRETO: nausea, shortness of breath, vomiting, muscle cramps, weakness, seizures or swelling. 

Risk of wound healing problems: Wounds may not heal properly during treatment with GAVRETO. Patients should tell their healthcare provider if they plan to have any surgery before or during treatment with GAVRETO. Patients should not take GAVRETO for at least 5 days before surgery. Healthcare providers should tell patients when they may start taking GAVRETO again after surgery.

Before taking GAVRETO, patients should tell their healthcare provider about all of their medical conditions, including if they: 

  • have lung or breathing problems other than lung cancer. 
  • have high blood pressure 
  • have bleeding problems  
  • plan to have surgery 
  • are pregnant or plan to become pregnant. GAVRETO can harm their unborn baby. 

Females who are able to become pregnant: 

  • Healthcare providers will do a pregnancy test before they start GAVRETO.
  • Should use an effective form of non-hormonal birth control (contraception) during treatment with GAVRETO and for 2 weeks after the final dose of GAVRETO. 
  • Birth control methods that contain hormones (such as birth control pills, injections or transdermal system patches) may not work as well during treatment with GAVRETO. 
  • Patients should talk to their healthcare provider about birth control methods that may be right for them during this time. 
  • Patients should tell their healthcare provider right away if they become pregnant or think they might be pregnant during treatment with GAVRETO. 
  • Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment and for 1 week after the final dose of GAVRETO. 
  • are breastfeeding or plan to breastfeed. It is not known if GAVRETO passes into breast milk. Patients should not breastfeed during treatment and for 1 week after the last dose of GAVRETO. 

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. GAVRETO may affect the way other medicines work, and other medicines may affect how GAVRETO works. 

The most common side effects of GAVRETO include: constipation, decreased levels of phosphate in the blood, high blood pressure, decreased levels of calcium in the blood, tiredness, decreased levels of body salt (sodium) in the blood, muscle and joint pain, diarrhea, abnormal liver function blood tests, and decreased white blood cell, red blood cell, and platelet counts. 

GAVRETO may affect fertility in males and females, which may affect the ability to have children. Patients should talk to their healthcare provider if this is a concern for them. 

These are not all of the possible side effects of GAVRETO. Patients should call their doctor for medical advice about side effects. Patients may report side effects to the FDA at 1-800-FDA-1088. Patients may also report side effects to Genentech at 1-888-835-2555. 

Please see the accompanying full Prescribing Information and Patient Information for GAVRETO.

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

 

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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.