Obicetrapib

NewAmsterdam Pharma Company N.V., in partnership with the Menarini Group, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorisation for Ubeslo (obicetrapib 10 mg) and Evlarco (10 mg obicetrapib plus 10 mg ezetimibe fixed-dose combination). The recommendation covers the treatment of adults with primary hypercholesterolaemia, including both heterozygous familial hypercholesterolaemia (HeFH) and non-familial forms, as well as patients with mixed dyslipidaemia, offering a potential new oral treatment option for individuals who remain unable to achieve recommended low-density lipoprotein cholesterol (LDL-C) targets using existing therapies. The CHMP's positive opinion is based on data from NewAmsterdam Pharma's extensive clinical development programme, including the Phase 3 BROADWAY, BROOKLYN and TANDEM trials. The studies demonstrated that obicetrapib monotherapy reduced LDL-C levels by up to 40 percent compared with placebo, while the fixed-dose combination with ezetimibe achieved reductions of approximately 50 percent, with an overall safety and tolerability profile comparable to placebo. Commenting on the milestone, Michael Davidson, MD, Chief Executive Officer of NewAmsterdam Pharma, said the positive opinion represents an important step forward for patients who continue to face elevated cardiovascular risk despite current lipid-lowering therapies. He noted that the once-daily oral therapy has the potential to address a significant unmet need if approved by the European Commission. The recommendation will now be reviewed by the European Commission, which is expected to issue a final decision on marketing authorisation later this year. If approved, the medicines will receive a centralised marketing authorisation valid across all European Union member states, as well as Iceland, Liechtenstein and Norway. Elcin Barker Ergun, Chief Executive Officer of Menarini, welcomed the CHMP recommendation, stating that the company looks forward to making obicetrapib available to patients across Europe who require additional LDL-C lowering beyond currently available treatments. Under an existing licensing agreement, Menarini holds exclusive commercialisation rights for obicetrapib across Europe and is responsible for regulatory activities and commercial launch in the region. NewAmsterdam Pharma will receive tiered royalties on net sales and remains eligible for additional milestone payments tied to clinical, regulatory and commercial achievements. Obicetrapib is a novel, low-dose, oral cCholesteryl Ester Transfer Protein (CETP) inhibitor designed to overcome limitations associated with current LDL cholesterol-lowering therapies. Beyond the completed Phase 3 studies, the therapy continues to be evaluated in several ongoing late-stage clinical programmes, including the PREVAIL cardiovascular outcomes trial, as well as the REMBRANDT and RUBENS studies. The announcement comes as cardiovascular disease continues to be the leading cause of mortality worldwide. Despite the widespread use of statins and other lipid-lowering therapies, many patients remain above recommended LDL-C targets, underscoring the continued need for more effective and well-tolerated treatment options to reduce residual cardiovascular risk.

The EMA's drug advisory panel backed a dozen medicines for approval at its July meeting, including Johnson & Johnson's IL-23 antagonist Icotyde (icotrokinra) for plaque psoriasis, Roche's ocular implant Susvimo (rabinizumab) for wet age-related macular degeneration (wAMD), and several cholesterol-lowering therapies.Among the more closely watched decisions, the Committee for Medicinal Products for Human Use (CHMP) recommended Icotyde for adults and adolescents aged 12 years and older with moderate-to-severe plaque psoriasis. If approved by the European Commission, Icotyde would be the first oral medicine targeting the Il-23 receptor available in the region, and expand a class that is dominated by injectables at the moment.The drug was approved in the US in March, with J&J recently saying its product is off to a strong commercial start. For related analysis, see Physician Views Results: J&J's Icotyde may have an edge on Takeda's TYK2 hopeful and Spotlight On: As Stelara fades, J&J's IL-23 tag team steps up.The CHMP recommendation was supported by four Phase III trials involving roughly 2500 patients. Across three studies, between 50% and 57% of patients achieved at least a 90% reduction in Psoriasis Area and Severity Index (PASI 90) scores after 16 weeks, versus between 1% and 4% of placebo recipients. Additionally, 65% to 71% of those given Icotyde achieved clear or almost clear skin, compared with 8% to 11% for placebo.Twice-yearly refillsMeanwhile, the Susvimo recommendation covers its use in adults with wAMD whose disease has stabilised following intravitreal anti-VEGF therapy. The treatment combines ranibizumab, which blocks VEGF, with a surgically implanted refillable ocular device designed to continuously release the drug.The implant is refilled every six months and would reduce the burden of monthly intravitreal injections that have been the standard for ranibizumab-treated patients since the drug was first approved in Europe nearly 20 years ago. If ultimately cleared by the European Commission, Susvimo would become the first implant of its kind approved in the EU.The recommendation was based on a Phase III study of 415 patients showing that Susvimo maintained visual and anatomical outcomes comparable to monthly ranibizumab injections. Common side effects included iritis, conjunctival bleb leak, cataract, vitreous floaters, conjunctival haemorrhage, conjunctival hyperaemia, eye pain and headache.Originally approved in the US for wAMD in 2021, Susvimo has since had its label expanded there to include diabetic macular oedema and diabetic retinopathy.Trio of anti-cholesterol drugsCHMP also backed approval of several cholesterol treatments for adults, including NewAmsterdam Pharma and Menarini's Ubeslo, a once-daily oral non-statin therapy containing low-dose CETP inhibitor obicetrapib, as well as Evlarco, a fixed-dose combination containing obicetrapib plus ezetimibe.Those positive opinions recommend the drugs for patients with primary hypercholesterolemia, both heterozygous familial and non-familial or mixed dyslipidemia based on Phase III data from the BROADWAY, BROOKLYN and TANDEM trials, which demonstrated significant LDL-C reductions reaching up to 40% with Ubeslo monotherapy and about 50% with Evlarco, when compared to placebo (see – KOL Views Q&A: NewAmsterdam's obicetrapib will elbow into LDL space pending two unknowns, says leading cardiologist).CHMP also adopted a positive opinion for LIB Therapeutics' Lyrokaul (lerodalcibep), an injection that patients can self-administer monthly. The third-generation PCSK9 inhibitor was approved by the FDA in December as Lerochol, based on data from the Phase III LIBerate programme showing sustained LDL-C reductions of 60% or more in patients with or at high risk of cardiovascular disease, and 50% or more in those with heterozygous familial hypercholesterolemia who have more severe LDL-C elevations.A first for cALDAmong medicines for rare diseases, CHMP recommended approval under exceptional circumstances for Minoryx Therapeutics and Neuraxpharm's Nezglyal (leriglitazone) to treat cerebral adrenoleukodystrophy (cALD) in patients aged two to 12 years with gadolinium-negative brain lesions.The opinion was based on the Phase II/III NEXUS study, where Nezglyal achieved the primary endpoint of clinical and radiological arrested disease at week 96 or at a visit prior to haematopoietic stem cell transplant, as well as additional real-world evidence from compassionate-use programmes.If regulators give the green light, expected in September, Nezglyal would become the first pharmacological treatment for cALD in the EU.Rare disease snubThe committee also issued negative opinions for three applications, including for Zevra Therapeutics' Meplyffa (arimoclomol citrate), which the company had been seeking approval for to treat Niemann-Pick disease type C in patients aged two years and older in combination with miglustat. "Due to the way the data had been handled and the results analysed, there were uncertainties about the reliability and robustness of the results. Moreover, no benefit was seen in terms of ambulation and cognition," the EMA said.The agency noted that data for a subgroup of patients who were also taking miglustat showed a treatment effect favouring Meplyffa, though this "was not considered robust since effectiveness had not been demonstrated in the overall population."Zevra, whose shares tumbled nearly 24% on Friday, said it is going to request a re-examination of the CHMP opinion.The oral heat shock protein amplifier was approved by the FDA in 2024 under the brand Miplyffa, after a bumpy regulatory journey. That decision was based on data from a 50-patient, placebo-controlled Phase II/III study where patients who received thrice-daily Miplyffa had slower disease progression than those on placebo, as measured by the 4-domain NPC Clinical Severity Scale (R4DNPCCSS).