RET Mutation-Positive Medullary Thyroid Cancer

The Gavreto baton is being passed on from Roche to Rigel Pharma. As Roche officially abandoned cancer drug Gavreto, its former partner Blueprint Medicines has found the RET inhibitor a new owner in the U.S. Rigel Pharmaceuticals will pay Blueprint $15 million to gain U.S. rights to Gavreto, the two companies said Thursday, just as Blueprint and Roche ended their collaboration. Under the new Rigel deal, Blueprint is also eligible to receive up to $102.5 million in future regulatory and commercial milestone payments, plus tiered royalties ranging from 10% to 30% depending on Gavreto’s sales level. In 2023, Gavreto generated about $28 million in U.S. sales, Rigel noted. Roche announced its intention to cut off Gavreto a year ago, with the termination going into effect today. After paying $775 million upfront to in-license the drug on the cusp of an FDA approval in 2020, Roche found that the drug wasn’t living up to its sales expectations. Then in July 2023, Roche decided to pull an accelerated approval for Gavreto in RET-mutant medullary thyroid cancer, citing an infeasible confirmatory trial. With Big Pharma support, Blueprint in January said it will discontinue work on Gavreto outside the U.S. and Great China, where CStone takes the charge. Thursday, Blueprint said it has also ended the ex-U.S. royalty interest deal it had signed with Royalty Pharma in mid-2022. The pact was based on Gavreto sales-related royalties from the Roche collaboration. For Rigel, Gavreto grows the California company’s oncology portfolio. The FDA in December approved Rigel’s Rezlidhia—which Rigel in-licensed from Forma Therapeutics—to treat IDH1-mutated acute myeloid leukemia. Rigel’s commercial offerings also include Tavalisse, which is indicated to treat adults with low platelet counts due to chronic immune thrombocytopenia. “The addition of Gavreto will be highly synergistic with our current product portfolio, leveraging our existing commercial infrastructure and enabling us to expand into solid tumors,” Rigel’s chief commercial officer, Dave Santos, said in a statement Thursday. Rigel will go up against Eli Lilly in the RET field. Last year, Lilly’s rival drug Retevmo ginned up $254 million in sales, including $175 million from the U.S. Retevmo also boasts a unique FDA nod to treat RET fusion-positive tumors regardless of their location. In October, phase 3 data showed that Retevmo reduced the risk of progression or death by 53.5% compared with the combination of Merck & Co.’s Keytruda and chemotherapy in patients with newly diagnosed RET fusion-positive non-small cell lung cancer. The Lilly med also aced its own confirmatory trial in RET-mutant medullary thyroid cancer. By comparison, Gavreto’s phase 3 AcceleRET-Lung trial in front-line RET fusion-positive NSCLC has yet to read out. Rigel and Roche have entered a transition period, in which Roche’s Genentech will still help ensure that patients can access Gavreto without interruption. Rigel expects to complete the transition and start recognizing sales from Gavreto in the third quarter of 2024. For its part, Blueprint expects the wind-down will significantly lower its operating expenses around Gavreto, though with little impact on the company’s overall numbers. Blueprint is currently focused on the systemic mastocytosis treatment Ayvakit, for which the company just dialed up the peak sales target to $2 billion.

Partnership creates new research award to help people living with all types of RET-positive cancer WASHINGTON, Jan. 25, 2024 /PRNewswire/ -- LUNGevity Foundation is proud to announce the 2024 Request for Applications (RFA) for our first pan-cancer research award program— the RETpositive/LUNGevity Translational Research Award for RET-positive Cancer. Changes in the RET gene are found in several cancers. RET rearrangements, in which a piece of the RET gene is fused to another gene, are found in 1% to 2% of non-small cell lung cancer, papillary thyroid cancer, and cancers of the colon, breast, and other organs. RET mutations are found in medullary thyroid cancer. Currently, two RET tyrosine kinase inhibitors are approved for the treatment of cancers carrying the RET biomarker. In this award program, RETpositive, a patient-led advocacy group focused on increasing awareness and supporting research for RET-positive cancers, seeks to fund high-impact research that transforms the future for all patients diagnosed with RET-positive cancer by changing RET-positive cancer into a chronic or curable condition. "Because RET biomarkers can be found in so many different cancers, and each individual cancer may be rare, it has been difficult to gather interest in funding RET cancer research by the large federal research funding organizations," said Dr. Hilary Hammell of RETpositive. "This RFA is a great example of how patient-centric organizations like RETpositive and LUNGevity can raise funds and awareness to fill the gap. Without this award program, it's likely this research wouldn't happen. As a pan-RET cancer group, our community is invested in driving this research." Projects funded in 2024 are expected to have a direct impact on the outcomes of patients with advanced RET-positive cancer. In keeping with the mission of RETpositive, proposals focusing on multiple types of RET-positive cancers or with a clear impact on multiple types of RET-positive cancers will be given priority. Each award will be a maximum of $100,000 over two years ($50,000 per year). "Over the past two decades, we've seen progress in lung cancer treatments paving the way for treatments in many other types of cancer," said Upal Basu Roy, PhD, MPH, executive director of LUNGevity Research. "But there is also much to be learned from other types of cancers when thinking about treating lung cancer. The intention of this research award is to bolster pan-cancer collaborations and cross-pollinate the best ideas to improve outcomes for patients with all types of RET-positive cancers, including lung cancer." RETpositive and LUNGevity successfully partnered in 2022 to fund research focused on RET-positive lung cancer. LUNGevity is honored to be chosen by RETpositive for the second time, to assist with the scientific review process of the grant submissions and to fund the selected research projects. Letters of intent must be submitted by February 9, 2024. Additional details about the RFA for this award are available at Applying for a LUNGevity Award | LUNGevity Foundation. About RETpositive RETpositive is a 501(c)(3) patient-driven group that aims to improve the quality of life and life expectancy of RET-positive cancer patients through increased awareness, community support and advocacy, and medical research funding for RET-driven cancer. For more information about RETpositive, please visit About LUNGevity Foundation LUNGevity, the nation's leading lung cancer organization, is transforming what it means to be diagnosed and live with lung cancer. LUNGevity seeks to make an immediate impact on quality of life and survivorship for everyone touched by the disease—while promoting health equity by addressing disparities throughout the care continuum. Through research, we use an innovative and holistic approach to finding lung cancer earlier when it is most treatable; advance research into new treatments so people may live longer and better; and ensure a diverse, vital pipeline of investigators for the future of the lung cancer field. Through advocacy, we foster groundbreaking collaborations to ensure all people have access to screening, biomarker testing, and treatment breakthroughs. Through community, we educate, support, and connect people affected by lung cancer so that they can get the best healthcare and live longer and better lives. Comprehensive resources include a medically vetted and patient-centric website, Patient Gateways for specific types of lung cancer, a toll-free HELPLine for personalized support, international survivor conferences, and tools to find a clinical trial. All these programs are designed to help us achieve our vision—a world where no one dies of lung cancer. LUNGevity Foundation is proud to be a four-star Charity Navigator organization. Please visit to learn more. About Lung Cancer in the US About 1 in 16 Americans will be diagnosed with lung cancer in their lifetime. More than 238,000 people in the US will be diagnosed with lung cancer this year. About 60%-65% of all new lung cancer diagnoses are among people who have never smoked or are former smokers. Lung cancer causes more deaths than the next two deadliest cancers (colorectal and pancreatic) combined. Only 25% of all people diagnosed with lung cancer will survive 5 years or more, but if it's caught before it spreads, the chance of 5-year survival improves dramatically. SOURCE LUNGevity Foundation

Blueprint Medicines is deprioritising some lung cancer programmes, citing an "evolving external landscape, emerging clinical data and partnering considerations." In an update at the ongoing JP Morgan healthcare conference, Blueprint said it would be scaling back Gavreto (pralsetinib) in certain markets, and culling a pair of early-stage assets.Last year, Roche terminated a collaboration between the companies due to strategic considerations and handed back global commercialisation and development rights for Gavreto, which is approved in the US to treat RET fusion-positive populations of non-small-cell lung cancer (NSCLC) and thyroid cancer. Gavreto had also received FDA accelerated approval for RET-mutant medullary thyroid cancer, but the partners withdrew the oral RET inhibitor for the indication last summer.Another partner to the rescue?Citing a lack of global infrastructure in lung and thyroid cancer, Blueprint now says it has decided to discontinue global development and marketing of Gavreto in territories excluding the US and China. It expects to begin winding down activities in the first quarter of 2024. An alternate partner for Gavreto in the US may be waiting in the wings, however; Blueprint said it is working with the parties involved to define a scenario that would allow the drug to continue to be available in the country.The move won't affect the $175-million upfront payment Blueprint received under a 2022 financing agreement with Royalty Pharma.Meanwhile, Blueprint also hinted that "emerging clinical data" spurred a decision to discontinue investing in the early-stage therapies BLU-945 and BLU-451 for EGFR-mutant NSCLC. The company got hold of BLU-451 via its purchase of Lengo Therapeutics in 2021 for up to $465 million, elbowing its way into an increasingly crowded niche within lung cancer.It is now considering different options for the assets, including potential out-licensing. That leaves BLU-525, another EGFR inhibitor, as Blueprint's sole pipeline candidate for lung cancer, according to its website.