Ibrutinib

Chinese authorities are already reviewing filings for potential approval of BeOne Medicines’ sonrotoclax. \n A phase 1/2 trial of BeOne Medicines’ sonrotoclax has hit its primary endpoint, furthering the biotech’s plans to launch the first BCL2 inhibitor for use in mantle cell lymphoma (MCL).The single-arm study enrolled 125 adults with relapsed or refractory MCL. Participants had previously tried anti-CD20 therapy and a BTK inhibitor. The study met its overall response rate primary endpoint and, in BeOne’s words, “showed promising results across several secondary efficacy endpoints, including complete response rate, duration of response and progression-free survival,\" according to an Aug. 29 release.BeOne is yet to share data from the trial but is confident enough in the results to start preparing to share its findings with the FDA and other global regulatory authorities. An approval for the candidate would establish BeOne in an indication that is free from competition from the leading in-class rival.Sonrotoclax hits the same target as AbbVie’s Venclexta. Pharmacyclics, part of AbbVie, ran a phase 3 trial to test Venclexta in combination with the BTK inhibitor Imbruvica in MCL. The regimen improved progression-free survival but never came to market. AbbVie and its partner Johnson & Johnson voluntarily withdrew Imbruvica in previously treated MCL in 2023. Having designed a BCL2 inhibitor that it claims is 14-fold more potent than Venclexta, BeOne identified the MCL market as one of the opportunities open to its drug candidate. Chinese authorities are already reviewing a filing for approval of sonrotoclax in relapsed or refractory MCL.Sonrotoclax is also being reviewed in China as a treatment for chronic lymphocytic leukemia and small lymphocytic lymphoma. Meanwhile, BeOne is testing the BCL2 inhibitor as a monotherapy and in combination with molecules including zanubrutinib and BGB-16673 in other blood cancers, reflecting its belief that it has unlocked multiple markets by trying to improve on Venclexta’s ramp-up and pharmacokinetics. 

BeOne doesn’t expect any meaningful impact this year from U.S. tariffs on pharmaceuticals because of the natural flow of inventory, the company’s CFO Aaron Rosenberg said. After beating AstraZeneca’s Calquence in quarterly revenue for the first time at the end of 2024, BeOne Medicines’ Brukinsa has pulled further ahead.Brukinsa’s second-quarter sales reached $950 million, which topped analysts’ expectations by about 5%. That compares with $872 million for Calquence during the same three-month stretch.The $78 million difference between the two newer BTK inhibitors marked an expansion from the $30 million advantage that Brukinsa had on Calquence in the first quarter of this year.“With our strengthening market position, we have seen competition aggressively discounted,” BeOne CFO Aaron Rosenberg said on an investor call Wednesday. “Despite this, given our broad access strategy and having protected class status, the vast majority of patients have unfettered access to Brukinsa and an even greater number achieve access upon appeal.”Despite its competitor’s discount strategy, BeOne expects stable Brukinsa U.S. net pricing for the rest of 2025, Matt Shaulius, general manager of North America, said on the call.“What we were conveying today is we are well aware of the environment,” Rosenberg said in an interview with Fierce Pharma after the investor call. “Our priorities are ensuring open access, but doing it in a way that recognizes the value of our innovations.”Brukinsa’s differentiated profile has been driving volume growth in the market, Rosenberg said.The medicine’s performance helped BeOne generate net income of $94 million during the second quarter after the company became profitable for the first time under GAAP standards in the first three months of 2025.BeOne officially changed its name from BeiGene and redomiciled from the Cayman Islands to Switzerland in May.The move was about the maturity of the company, Rosenberg said, describing Switzerland as a welcoming environment for the biopharma industry with its reliable trade and tax treaties.BeOne’s relocation comes as the entire biopharma industry braces for U.S. tariffs on pharmaceutical imports. During a CNBC interview Tuesday, President Donald Trump said the administration will install a small tariff on pharmaceuticals initially, growing to 150% in a year or a year and a half before eventually reaching 250%. The rate will be announced “within the next week or so,” he said. BeOne’s guidance, including an upgraded outlook of a gross margin in the mid- to high-80% range for 2025, already incorporates what’s known today about tariffs, Rosenberg said on the investor call.“That impact has largely been mitigated by how we’ve globalized and regionalized our supply chain,” the CFO said, pointing to the company’s U.S. production for Brukinsa and a new biologics facility in Hopewell, New Jersey, for potential commercial supply of Tevimbra and future medicines.BeOne currently partners with contractors to handle Brukinsa drug production and packaging in the U.S., but it does need to import active pharmaceutical ingredients, Rosenberg told Fierce. The company has two FDA-approved sources for Brukinsa API in the EU and China, and it’s looking to add another source in Europe.Meanwhile, the BeOne leadership team is monitoring the upcoming results from the Trump administration’s Section 232 investigation into the national security implications of pharmaceutical imports. But Rosenberg said the firm doesn’t expect any meaningful impact this year because of the natural flow of inventory.“We’ll assess what the results of those investigations and policy that comes from it,” Rosenberg said. “Like everything in our business, we’ll be agile and make sure we’re being as financially efficient as we can be, and most important, that we have a supply chain that can serve patients around the world.”In another potential regulatory uncertainty in the U.S., President Trump recently upped the ante on the implementation of the “most favored nation” drug pricing policy that aims to match the costs of prescription drugs in the U.S. to the lowest price offered in other developed countries.Companies like Novo Nordisk, Eli Lilly and Pfizer/Bristol Myers Squibb have rolled out direct-to-consumer models offering some of their medicines at lower costs directly to patients, and Roche has said it’s considering this approach.BeOne is studying the DTC model, but Rosenberg said it’s hard to say how suited it is to cancer drugs, including Brukinsa.“I think there potentially is applicability,” Rosenberg said. “Like anything in our business, we will assess it. And if there’s value there, and it helps patients, [it’s] something we’ll look at seriously."Meanwhile, additional competition is brewing for Brukinsa.Last week, Eli Lilly announced that its noncovalent BTK inhibitor Jaypirca matched up to AbbVie and Johnson & Johnson’s first-to-market covalent BTK drug Imbruvica in overall response rate in front-line chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The Lilly med also showed a nominal superiority, although the trial design didn’t give this analysis statistical power. But Lilly’s positive Bruin CLL-314 readout for Jaypirca is “highly unlikely to be practice-changing,” BeOne’s R&D chief, Lai Wang, Ph.D., said on the call.For one, the Lilly study has not reported progression-free survival data, which Lai said is the gold standard in first-line CLL/SLL. In addition, Jaypirca should be compared with Brukinsa, Wang argued, because BeOne’s medicine is the true standard now in the treatment-naïve setting. What’s more, given that CLL is a chronic disease, and because Lilly’s proposing continuous treatment, the company needs a longer follow-up to truly convince people of Jaypirca’s therapeutic benefit, Wang said.Because Jaypirca is currently the only noncovalent BTK that can be used sequentially after failure on a covalent BTK inhibitor, Wang expects doctors will reserve the Lilly drug for second-line treatment based on existing data.During Wednesday’s call, Wang again shrugged off first-line CLL competition from AstraZeneca’s fixed-duration option of two Calquence combinations, which have been approved in the EU and are under review at the FDA. On the fixed-duration front, BeOne is advancing its phase 3 Celestial 301 trial that pairs Brukinsa with the company’s BCL-2 inhibitor sonrotoclax. Editor's Note: The story was updated with the correct information on the source of BeOne's Brukinsa API supplies.