Zidesamtinib

GSK CEO Luke Miels said the deal “will strengthen our operating profit ... through the dolutegravir loss of exclusivity period.”\n GSK has struck a deal to buy Nuvalent for $10.6 billion, securing two near-approval cancer therapies that could challenge products from Roche, Pfizer and other drugmakers. The FDA is set to rule on whether to approve Nuvalent’s ROS1 inhibitor zidesamtinib in September and reach a decision on the biotech’s ALK inhibitor neladalkib in November. With two near-approval assets, plus a phase 1 HER2 inhibitor and preclinical programs, the deal offers near-term growth drivers to ease the pressure GSK could face as generics erode sales of a key HIV drug from 2028 to 2030.“Subject to FDA approvals, the acquisition will deliver revenue growth from 2027. This is what our investors have been asking,” GSK CEO Luke Miels said on a call with the media early Tuesday morning. “It will strengthen our operating profit for GSK through the dolutegravir loss of exclusivity period.”Nuvalent filed for FDA approval of zidesamtinib in ROS1-positive non-small cell lung cancer (NSCLC) patients who have previously received a tyrosine kinase inhibitor (TKI). Before accepting GSK’s offer, the biotech said (PDF) it planned to apply to expand the label in the second half of the year to include patients without prior TKI exposure.Zidesamtinib could pose a threat to Pfizer’s TKI inhibitor Xalkori, which Nuvalent named as the first-line standard of care. Treatment guidelines also recommend (PDF) Roche’s Rozlytrek, Bristol Myers Squibb’s Augtyro and Nuvation Bio’s Ibtrozi, especially against brain metastases. Nuvalent has identified improved durability and reduced central nervous system side effects as ways to differentiate zidesamtinib.The FDA is reviewing neladalkib in TKI-pretreated, ALK-positive NSCLC. Nuvalent is enrolling patients in a phase 3 trial that is pitting the ALK inhibitor against Roche’s Alecensa in TKI-naive patients. Alecensa is the first-line standard of care and Pfizer’s Lorbrena is the preferred second-line treatment, according to Nuvalent. Miels named a recent seven-year analysis of Pfizer’s phase 3 Crown study as a driver of GSK\'s interest in neladalkib. The data showed Pfizer’s Lorbrena “has very good efficacy but a very, very difficult side effect profile to manage,” Miels said. Because patients are often relatively young, the downsides to a drug that impacts their ability to care for their kids and lead active lives are particularly severe, Miels said.The duration of treatment factored into GSK’s valuation of Nuvalent. The target mutations are found in a small subset of patients—about 3% to 5% of people with NSCLC are ALK-positive—but patients who are eligible for treatment spend longer on the drugs than is typical for many cancers. That means there are “very long tails to these products,” Miels said. About 1% to 3% of patients have ROS1 mutations. GSK sees “multiblockbuster potential” for zidesamtinib and neladalkib, leading it to agree to pay $124 a share to buy the biotech. Nuvalent’s stock closed at $88.49 on Monday. The outlay is well beyond the $2 billion to $4 billion deal range that Miels targeted after becoming CEO early this year. Yet the GSK leader maintained that the Nuvalent buyout is in line with the types of deals the company has been pursuing and striking. The difference is that instead of paying up to $4 billion for a biotech with one attractive asset, GSK is paying $10.6 billion for a company with multiple molecules of interest. “If you take apart the components, it\'s consistent with our approach so far,” Miels said. If zidesamtinib or neladalkib wins FDA approval, the deal will accelerate GSK’s entry into lung cancer and provide a potential launchpad for its B7-H3 antibody-drug conjugate (ADC) risvutatug rezetecan. GSK started a phase 3 trial of the ADC in small cell lung cancer last year.