Lutetium Dotatate LU-177

Bristol Myers Squibb said Monday that the asset at the centre of its $4.1-billion purchase of RayzeBio — an experimental radiopharmaceutical therapy (RPT) dubbed RYZ101 — hit the primary endpoint of a Phase III study for certain patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). The ACTION-1 trial enrolled patients with somatostatin receptor-positive GEP-NETs who have progressed following treatment with lutetium-177 (Lu177)-based therapy. Participants were randomised to receive investigator's choice of standard of care or RYZ101, which comprises dotatate bound to the alpha-emitting radioisotope actinium-225. Top-line results from a planned interim analysis showed that the study achieved its main goal, with RYZ101 demonstrating a statistically significant and clinically meaningful improvement in progression-free survival. BMS noted that safety results were consistent with RYZ101's known profile. "The improvement in progression-free survival is a defining moment for RYZ101," remarked Amreen Husain, RayzeBio's chief medical officer. "These are the first results from a Phase III trial of an alpha-isotope based targeted RPT in any indication, and we are moving with urgency to bring these data to the FDA." Novartis' Lutathera (Lu177 dotatate) is currently approved for the treatment of patients with somatostatin receptor-positive GEP-NETs, with Curium more recently gaining FDA clearance in the same indication for Bexlutry (Lu 177 dotatate), a radioligand equivalent that references the Swiss drugmaker's product. Simron Singh, principal investigator of the ACTION-1 study, noted that while Lu177-based therapy is widely used for treating GEP-NETs, "the vast majority of patients will eventually progress," and, up until now, there has been no randomised Phase III evidence to guide the next steps. Along with ACTION-1 — detailed results of which are expected to be presented at a future medical meeting — RYZ101 is also being evaluated in earlier-stage trials in hormone receptor-positive metastatic breast cancer. The content above comes from the network. if any infringement, please contact us to modify.

Bristol Myers Squibb has reported phase 3 wins in a lung disease and a solid tumor, taking two steps on its path toward post-patent cliff growth. One phase 3 trial, Aloft-IPF, tested the LPA1 antagonist admilparant in adults with idiopathic pulmonary fibrosis (IPF). The other study, Action-1, evaluated a radiopharmaceutical therapy, RYZ101, in people with SSTR-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Both trials met their primary endpoints, albeit without fully resolving doubts about the programs. The 60 mg dose of admilparant had a statistically significant effect on forced vital capacity, a measure of lung function, at Week 52. Yet, while that result ensured a primary endpoint hit, the higher 120-mg dose failed to clear the bar for statistical significance. BMS has yet to share data from the trial. The “totality of the findings” supports admilparant’s potential as a clinically meaningful first-in-class treatment, BMS said. The drugmaker plans to talk to regulators about filing for approval of admilparant. In a note in August, Guggenheim Securities analysts called admilparant a $5 billion-plus opportunity for BMS in IPF and progressive pulmonary fibrosis. Admilparant was well tolerated, and discontinuations caused by adverse events were low and similar to placebo, BMS said. References to liver toxicity and a patient death in a protocol amendment recently raised concerns about admilparant’s safety. While BMS made no mention of liver safety in this morning's topline readout, William Blair analysts explained in a note this morning that the pharma's management had confirmed that the case of acute liver injury was in the 120 mg arm, and the adjudication committee had “determined it was unlikely related to study treatment.” Meanwhile, BMS announced that Action-1 had hit its primary endpoint at a planned interim analysis. Progression-free survival was significantly longer on RYZ101 than on investigator's choice of standard of care, teeing up talks with the FDA about the next steps toward a regulatory submission. Again, BMS has yet to share data from the trial. When it came to safety, the drugmaker only said the results were consistent with RYZ101’s known profile. The readout advances BMS’ efforts to establish RYZ101 as an option for patients who progress on Lutathera, one of Novartis’ Lutetium-177 (Lu177)-based radiopharmaceuticals. GEP-NET patients entered Action-1 after progressing on Lu177-based therapy. Lu177 is a beta emitter, while RYZ101 delivers an alpha emitter, actinium-225. Launching admilparant and RYZ101 could give BMS growth drivers at a time when its cornerstone drugs are nearing the ends of their life cycles. Eliquis and Opdivo accounted for more than half of BMS’ sales in the second quarter, but both drugs could lose market exclusivity in the U.S. in 2028. With Cobenfy, the schizophrenia drug BMS acquired through its $14 billion Karuna Therapeutics buyout, yet to make a significant revenue contribution, the drugmaker is under pressure to find other growth drivers. The wins for admilparant and RYZ101 go some way to easing the pressure, but BMS’ path to long-term growth remains dotted with pitfalls. Key readouts on the horizon include the phase 3 Librexia AF trial of milvexian, an oral FXIa inhibitor, in atrial fibrillation. Investors seemed in two minds about this morning's data, initially sending BMS' stock up 3.5% when the markets opened on Monday. But after an hour of trading, the stock was down 3% on Friday's closing price. William Blair analysts attributed the initial stock bump to the win for admilparant, a drug they estimated could reach sales of $1.3 billion for IPF in 2032. “While there will be some lingering questions on dose response and the magnitude of benefit for admilparant from the Aloft-IPF study, we believe the success of the 60 mg dose is likely to open a blockbuster opportunity given we view the novel mechanism and non-overlapping toxicities with current therapies in IPF as positive for combination approaches,” the analysts wrote in a Monday morning note. Where Big Pharma is placing its bets is one of the hot topics being discussed at Fierce Biotech's high-impact event in London next month. Find out more information and register by clicking on the banner below: