Entrectinib

GSK could see speedy returns from its $10.6-billion buy of Nuvalent, thanks to an FDA nod Wednesday for the first programme from the takeout, Jideytro (zidesamtinib). The US regulator approved the ROS1 selective inhibitor for adults with locally advanced or metastatic ROS1-positive non–small-cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor. The purchase, announced in June and officially closed last week, handed GSK a pair of lung cancer treatments already under review at the FDA. Jideytro's clearance came about two months ahead of its Sept. 18 PDUFA date, while the second asset, ALK-selective inhibitor neladalkib, is nearing a Nov. 27 decision deadline for ALK-positive NSCLC (see – Spotlight On: The ASCO moment that sealed GSK's biggest deal in years)."The rapid progression of Jideytro from development to approval reflects both the strength of the underlying science and the urgent need for additional effective and tolerable treatments for ROS1-positive lung cancer," said GSK's Chief Scientific Officer Tony Wood. Analysts have projected nearly $2 billion in peak annual sales for the drug, a next-generation blood-brain-barrier–penetrant inhibitor designed to broadly address ROS1 resistance mutations while remaining highly target-selective. However, to reach that sales goal, Jideytro will have to overtake several competitors in the ROS1-positive NSCLC space, including Roche's Rozlytrek (entrectinib), Bristol Myers Squibb's Augtyro (repotrectinib) and Nuvation's Ibtrozi (taletrectinib) — though analysts at Jefferies have argued that the candidate's improved tolerability, as well as activity against resistance mutations and in the central nervous system, could lift provide the product with a differentiating edge (see – Spotlight On: Three things to watch at GSK). Response rate resultsJideytro was approved based on results from the Phase I/II ARROS-1 trial, which enrolled patients with previously treated, advanced ROS1-positive NSCLC. The therapy achieved an objective response rate (ORR) of 44% in the overall 117-patient population, while a subgroup of 55 patients who had received only one prior ROS1 inhibitor experienced an ORR of 51%. In patients treated with two or more prior ROS1 inhibitors, the ORR was 38%. In addition, Jideytro demonstrated a 69% duration of response rate at 12 months. A pooled safety analysis comprising 446 participants showed that the therapy's most common adverse reactions — those occurring in 15% or more of patients — were oedema, peripheral neuropathy, constipation, fatigue and dyspnoea.

GSK could quickly begin making money on a drug it just acquired in one of the years biggest biopharmaceutical acquisitions.The British drugmaker on Wednesday won approval from U.S. regulators to begin selling a therapy known as Jideytro. The Food and Drug Administration cleared that treatment, formerly called zidesamtinib, in people whose metastatic non-small cell lung cancer has alterations in the gene ROS1 and who previously received another targeted therapy. The nod comes well ahead of a Sept. 18 decision deadline, following a pair of breakthrough therapy and orphan drug designations that can accelerate reviews.For GSK, the approval kickstarts a return on an acquisition it completed just last week. In that deal, GSK paid $10.6 billion for Nuvalent, the maker of Jideytro as well as another medicine, neladalkib, thats currently under FDA review. That purchase was, by far, GSKs largest over the last eight years, BioPharma Dive data show.The Nuvalent buyout was also part of a broader effort by GSK best known for its HIV medicines, respiratory disease drugs and vaccines to grow an oncology business. Dealmaking helped GSK acquire the cancer medicines Jemperli and Zejula and the multiple myeloma treatment Blenrep. A partnership with Chinas Hansoh Pharma and buyout of startup IDRx yielded a combined three other medicines that are now in advanced testing. Jefferies analyst Michael Leuchten estimated in a recent research note that the Hansoh and IDRx drugs alone have a peak revenue opportunity of more than 6 billion pounds, or $8 billion.With Jideytro, meanwhile, GSK aims to make inroads in an area with plenty of competition and somewhat unclear sales potential. About 2% of people with non-small cell lung cancers are positive for ROS1 mutations. Multiple drugs like Pfizers Xalkori and Roches Rozlytrek are available but havent sold particularly well, raising skepticism about the commercial outlook for newer entrants.Jideytro is a next-generation alternative. Prior to its acquisition, Nuvalent had touted the medicines potential to last longer and carry fewer side effects than other therapies while also sidestepping drug resistance. GSK made similar assertions in its statement Thursday, pointing to Jideytros high selectivity, broad coverage of resistance mutations and ability to combat the brain metastases that are a leading cause of disease progression.Some 50,000 people worldwide are diagnosed with the disease, and many could stay on treatment for several years, the company said.The rapid progression of Jideytro from development to approval reflects both the strength of the underlying science and the urgent need for additional effective and tolerable treatments for ROS1-positive lung cancer, Chief Scientific Officer Tony Wood said in GSKs statement. '