Ranibizumab (Genentech)

Across the pond, European regulators handed down a pair of pivotal approval recommendations this week, making way for a new front in Novo and Eli Lilly’s oral GLP-1 showdown and endorsing Revolution Medicines’ potential pancreatic cancer game changer, which has received some investor scrutiny of late following the recent release of FDA review documents in the U.S. Both decisions—which cover Lilly’s oral GLP-1 treatment Foundayo and RevMed’s RAS inhibitor Rasonque—came by way of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which has recommended six new drugs for approval and jockeyed for five label extensions in its latest wave of regulatory action. CHMP’s approval recommendations are not the end of the road for a drug application in the European Union, with the decisions still subject to final sign-off by the European Commission. However, formal approval often follows the human medicines committees’ blessing. The marketing recommendation for Lilly’s Foundayo, which leverages the orally delivered GLP-1 molecule orforglipron, addresses both obesity and Type 2 diabetes for adults, coming on the heels of the weight management-only EU endorsement that Novo received for its rival Wegovy pill back in May. Novo has long sold a separate version of oral semaglutide for diabetes under the brand name Rybelsus, which the medicine still carries in Europe. Novo retired the Rybelsus brand in the U.S. and relaunched a slight reformulation of oral semaglutide in Type 2 diabetes under the Ozempic pill moniker earlier this year. The new EU endorsement for Foundayo, meanwhile, applies to treatment of obesity or overweight in adults with at least one weight-related health problem. In diabetes, Foundayo can either be taken alone when metformin isn’t a good fit for patients, or together with other diabetes meds, the CHMP explained in a Friday release. The CHMP based its obesity green light on a pair of studies that found patients on Foundayo lost around 5% to 11% of their body weight after 72 weeks, dependent upon the exact dose received, versus a range of 2% to 2.5% on placebo. And in the four primary studies of Foundayo in Type 2 diabetes, Lilly’s GLP-1 tablet was linked to A1C reductions of around 1.2 to 1.9 percentage points—again dose-dependent—compared to a 0.4-to-0.8 percentage-point decline on placebo. Lilly also pitted its pill against AstraZeneca’s SGLT2 inhibitor Farxiga and Novo’s oral semaglutide at the 7- and 14-mg doses in Type 2 diabetes, coming out on top in those comparisons as well. Aside from the likely pent-up patient demand for another oral weight loss option in the EU, investors and industry watchers will be closely monitoring Foundayo’s performance in the transatlantic market. After gaining a notable market advantage over Novo’s bread-and-butter obesity injectable Wegovy with its own Zepbound in recent years, Lilly has struggled to gain a lead after launching second to Novo in the oral obesity drug space earlier this year. The other banner endorsement from the CHMP this week came for RevMed’s Rasonque as a second-line monotherapy in patients with metastatic pancreatic adenocarcinoma, rounding out a similar green light from the FDA in late August. Should Rasonque snare the European Commission’s blessing, it will become the first broad RAS-targeted treatment for this specific patient population in the EU, RevMed said in an Oct. 15 release. As in the case of the recent U.S. nod, RevMed leaned on its landmark RASolute 302 trial to support its approval ambitions in Europe. RevMed reported that Rasonque had doubled overall survival in the phase 3 study back in April and then revealed at ASCO that the RAS inhibitor had doubled progression-free survival , too, prompting a standing ovation from the conference’s sizeable audience. “Today’s positive CHMP opinion marks a major step toward making Rasonque available to eligible adults with metastatic pancreatic cancer in the European Union,” Mark Goldsmith, M.D., Ph.D., RevMed’s CEO, said in a statement. As major hopes ride on Rasonque, the drug faced some unexpected investor unease earlier this month with the release of FDA review documents, which led to questions about the drug’s positioning in a key KRAS subgroup. The shareholder jitters, which pressured RevMed’s stock last week, largely revolved around the medicine’s lower posted objective response rate in patients with KRAS G12D mutations, which represent the most common subtype of KRAS mutations in pancreatic cancer. Still, multiple analyst shops flagged the stock movement as an overreaction, with the team at Leerink Partners noting last week that the subgroup analysis “doesn’t change anything for Rasonque.” In a statement to Fierce, a RevMed representative stressed that overall survival remains “the gold standard endpoint in oncology and is what matters most to patients and physicians, particularly in pancreatic cancer.” Moreover, the analysts pointed to apparent other benefits in Rasonque despite lower ORR numbers in G12D and another subgroup of patients. Beyond Rasonque and Foundayo, other drugs to win favor with CHMP this week included Ascendis’ Yuviwel for pediatric achondroplasia and Orphelia Pharma’s glioblastoma multiforme and malignant glioma med Kizfizo, which has orphan drug status in the U.S.—plus endorsements for two separate biosimilar referencing Roche’s Lucentis (ranibizumab) and the neutropenia med filgrastim. The regulatory body also put its weight behind label extensions for AstraZeneca’s avian influenza vaccine, as well as Novo’s insulin icodec-semaglutide combo for Type 2 diabetes, Kyinsu, plus Johnson & Johnson’s Talvey, Ionis’ Tryngolza and Pfizer’s Tukysa.