Flortaucipir F-18

Drug reviewers at the European Medicines Agency have given a thumbs up for Merck's PAH drug Winrevair and a second thumbs down to Apellis' geographic atrophy treatment Syfovre. For the second time in six months, Europe’s Committee for Medicinal Products for Human Use (CHMP) has given a thumbs down to Apellis’ Syfovre for the treatment of patients with geographic atrophy (GA) caused by age-related macular degeneration. In a release, Apellis noted that there were “multiple dissenting votes” by CHMP members to the opinion. The company added that it plans to seek a reexamination of the opinion, with a final decision expected in the fourth quarter of this year. “Although the studies showed that Syfovre slowed the growth of geographic atrophy lesions, this did not lead to clinically meaningful benefits for patients,” the CHMP said. “It was noted that benefits of a treatment should impact patients’ everyday functioning, and this was not demonstrated in the studies.” “In terms of safety,” the CHMP continued, “regular injections into the eye carry a significant risk of adverse events, including the development of other forms of AMD or inflammation in the eye, that could further worsen vision.”  In January of this year, the CHMP adopted its first negative opinion on Syfovre. The drug was approved by the FDA in February of 2023 and generated $275 million in sales last year despite early reports of inflammation for some users. In May, the company said that it holds an 85% share of the market in GA, but admitted to challenges with its launch. In the indication, Apellis is competing with Astellas’ Izervay, which has filed for approval in Europe. Mizuho Securities analyst Graig Suvannavejh noted that there was a 5% drop in Apellis' share price on Friday morning. "There have yet to be data convincingly demonstrating Syfovre use leading to clear, clinically meaningful functional benefit," Suvannavejh wrote in a note to clients. "Moreover, from a drug approval perspective, we view the European Medicines Agency as typically more conservative than the FDA. As such, we lower our probability of success for Syfovre's EU approval from 20% to 10%." Other CHMP rejections Syfovre was not the only drug that was beaten back by the CHMP more than once. The European drug reviewers have once again recommended not renewing the marketing authorization for PTC Therapeutics’ Translarna as a treatment for Duchenne muscular dystrophy. This negative opinion follows the European Commission’s May decision to not adopt the CHMP’s negative opinion from January. By that time, The CHMP had already reviewed and declined to renew the drug’s conditional nod twice. According to PTC, the scientific advisory group convened for the latest review concluded that the evidence of significant efficacy provided by the STRIDE trial "should not be ignored." And yet, the agency still maintained its previous stance. Now, PTC plans to request a reexamination of the CHMP’s third opinion. After that, the European Commission will make a decision. Based on the timeline of these procedures, PTC said it expects Translarna to remain on the market through the end of 2024 even if the negative opinion holds. Elsewhere, the CHMP also refused to recommend a marketing authorization for AB Science’s masitinib, a treatment for the nervous system disorder amyotrophic lateral sclerosis (ALS). The France-based company said it will ask for a reexamination. The CHMP also recommended that the marketing authorization for Advanz's Ocaliva be revoked for the treatment of patients with primary biliary cholangitis. Positive CHMP opinions Meanwhile, the CHMP this week issued positive recommendations for several therapies, including Merck’s blockbuster-to-be Winrevair for pulmonary arterial hypertension (PAH). Winrevair, which gained a high-profile approval from the FDA in March, is the first disease-modifying treatment for the condition. Winrevair, which was acquired by Merck in an $11.5 billion buyout of Acceleron in 2021, has been pegged by J.P Morgan analyst Chris Schott to achieve peak sales between $3 billion and $4 billion. The CHMP also recommended ARS Pharmaceuticals’ marketing application for the adrenaline nasal spray Eurneffy to be approved. It would become the first needle-free adrenaline option in Europe for the treatment of emergency Type 1 allergic reactions (anaphylaxis), which include those to food and insect bites. ARS expects to receive authorization from the EU in the third quarter and to launch Eurneffy in the fourth quarter. The company also hopes for approval of the product from the FDA, with a decision date set for October 2 of this year. The CHMP recommended Johnson & Johnson’s Balversa for the treatment of patients with unresectable or metastatic urothelial carcinoma, a type of bladder cancer. The FDA signed off on Balversa in the indication in January of this year, turning a 2019 accelerated approval into a full nod. Moderna’s respiratory syncytial virus (RSV) vaccine mRasvia has made the grade with the CHMP, too, gaining a recommendation for adults ages 60 and older. The shot, which was approved by the FDA four weeks ago, is the first mRNA vaccine targeting a pathogen other than the coronavirus to receive a positive opinion from the CHMP. Regeneron’s CD20xCD3 bispecific T-cell engager Ordspono (odronestamab) netted a positive opinion from the CHMP to treat two types of blood cancers—follicular lymphoma and diffuse large B-cell lymphoma. The thumbs up comes three months after the FDA sent two complete response letters to Regeneron for the same indications, questioning the timelines of the company’s confirmatory trials. The CHMP recommended Roche’s Piasky (crovalimab) for marketing authorization, just four days after the FDA endorsed it for patients age 13 and older with paroxysmal nocturnal hemoglobinuria (PNH), a rare, genetic life-threatening disorder of the immune system that causes premature breakdown of the red blood cells. The CHMP also has issued a positive opinion on Eli Lilly’s Tauvid (flortaucipir), the first drug used to image a characteristic of Alzheimer’s disease in the brain called tau pathology. The FDA signed off on Tauvid four weeks ago. Also making the grade from the CHMP was Celltrion’s Steqeyma, which is a biosimilar of J&J’s Stelara. It has been recommended for patients with Crohn’s disease, plaque psoriasis and psoriatic arthritis.

Pictured: Abstract visualization of human brain/iStock, bawanch An FDA advisory committee on Monday unanimously voted for the approval of Eli Lilly’s anti-amyloid antibody donanemab, concluding that the benefits outweighed the risk for Alzheimer’s disease patients. At the same time, thousands of physicians, technologists, lab professionals, scientists and others attended the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2024 annual meeting in Toronto. Many of the speakers at SNMMI 2024 discussed donanemab and other anti-amyloid drugs and the urgent need to properly diagnose Alzheimer’s so these therapies will benefit patients. Despite other targets, amyloid beta and tau remain critical to the Alzheimer’s treatment landscape, with Eisai and Biogen’s Leqembi in July 2023 becoming the first ever anti-amyloid antibody and disease-altering treatment to be granted traditional FDA approval. Mary Ellen Koran, assistant professor of radiology in the Nuclear Medicine Section at the Mayo Clinic Arizona, emphasized in an SNMMI 2024 presentation that the imaging of brain pathologies is critical, particularly with the advent of anti-amyloid drugs. “It turns out that clinically diagnosing Alzheimer’s disease is very difficult,” Koran said at SNMMI 2024. “Even in specialized dementia centers, there’s a misdiagnosis of Alzheimer’s disease of over a quarter of patients. This is really important now that we have therapies that are actually targeting these pathologies.” Koran pointed to a study published in JAMA Neurology that found as many as one-third of patients clinically diagnosed with mild to moderate Alzheimer’s disease had minimal amyloid accumulation in their brains and risked having limited or no benefit from anti-amyloid treatment. “If you’re giving them a drug based on clinical diagnosis, you’re not giving these patients the right drug, and you’re not giving the right patients the drugs for the clinical trials,” she said. “This is where imaging becomes so important.” The Amyloid PET Quandary Positron emission tomography (PET) scans are a particularly critical component of the diagnosis and treatment of Alzheimer’s disease (AD). Last week, ahead of Monday’s advisory committee meeting, FDA staffers noted that donanemab treatment “demonstrated a statistically significant effect on change from baseline in brain amyloid plaque as measured by PET.” The agency also said that “the use of reduction of amyloid plaques on PET as a surrogate endpoint [is] reasonably likely to predict clinical benefit in patients with early symptomatic stages of AD.” The Alzheimer’s Drug Discovery Foundation (ADDF) has called Lilly’s TRAILBLAZER-ALZ 2 donanemab trial “emblematic of a new era” in research in which patients most likely to benefit from treatment are identified in the early stages of AD. “A unique aspect of this trial was the use of both the Amyvid and Tauvid PET scans to enroll patients with confirmed amyloid plaques, allowing investigators to confirm clearance or reduction of the pathology in later scans,” according to ADDF. At SNMMI 2024, Koran similarly commented that in Lilly’s TRAILBLAZER-ALZ 2 trial, “there were multiple amyloid PET images taken throughout the course of treatment,” which is “pretty cool” for the Alzheimer’s imaging community as such “quantification” of images “may actually inform therapy.” On the reimbursement side, an October 2023 decision by the Centers for Medicare and Medicaid Services (CMS) expanded coverage of PET imaging for diagnosing AD, potentially enabling greater access to new therapies for patients. “It makes us, as nuclear medicine physicians, very relevant to the treatment of these patients,” Koran said. However, Satoshi Minoshima, chair of the Department of Radiology and Imaging Sciences at the University of Utah, provided a sobering assessment at SNMMI 2024 of the challenges facing anti-amyloid therapy in the U.S., including limited scanner capacity, shortages of radiologists and cognitive disorder specialists and unreliable PET interpretation. “Resource limitation is a major challenge for the health system,” Minoshima said, noting it’s a problem that will only get worse as anti-amyloid antibodies like donanemab come to market. The new CMS policy to pay for amyloid PET scans beyond clinical trials is already having a big impact. Minoshima provided a chart with the latest nationwide data on patient volume in the U.S., which showed a 5- to 10-fold increase since October 2023. “Amyloid PET imaging use is really escalating nationally,” he warned. It seems the dam is about to break. Greg Slabodkin is the news editor at BioSpace. You can reach him at greg.slabodkin@biospace.com. Follow him on LinkedIn.