Welcome to the Weekly Rundown where the DDN editors cover this week’s top biotech and pharma news.
Ulefnersen slows disease progression in Phase 3 ALS trial
Otsuka and Ionis Pharmaceuticals’ investigational RNA-targeted therapy ulefnersen has met the primary endpoint in a Phase 3 trial of FUS-associated amyotrophic lateral sclerosis (FUS-ALS), a rare and rapidly progressive form of the disease caused by mutations in the FUS gene. The FUSION study enrolled 89 patients, with 73 included in the primary analysis, and found that ulefnersen significantly slowed the combined measure of functional decline and survival at week 72 compared with placebo. The therapy also outperformed placebo on secondary measures, including a biomarker of neurodegeneration and time to death, permanent ventilation, rescue treatment, or withdrawal due to disease progression. Ulefnersen is designed to reduce the production of FUS protein by binding FUS pre-messenger RNA, including mutant forms that contribute to motor neuron degeneration. Otsuka plans to discuss the results with regulatory authorities and has launched an early-access program for eligible patients with genetically confirmed FUS-ALS who cannot participate in a clinical trial. There are currently no approved therapies specifically targeting the underlying genetic cause of FUS-ALS. – Bree Foster
Kyverna’s CAR T cell therapy appears effective over the long haul
On Thursday, Kyverna Therapeutics announced long-term data for their CAR T cell therapy, miv-cel, in the treatment of stiff person syndrome (SPS) and generalized myasthenia gravis (gMG). In SPS, over the course of one year, a single dose of miv-cel led to sustained improvements on a standard walking test and 92 percent of patients did not need to take chronic immunotherapies. In gMG, in a follow-up study up to 1.5 years, a single dose led to all seven patients achieving clinically meaningful improvements on a standard gMG assessment, and all remained off immunotherapies. In both indications, miv-cel was well-tolerated without safety concerns — a compelling result that comes on the heels of concerning safety signals, including three deaths, that led to paused autoimmune CAR T trials from Novartis and Bristol Myers Squibb earlier this month. "The durable clinical responses achieved in SPS and gMG, combined with a consistently favorable safety profile, set a new benchmark for autoimmune CAR T and reinforce miv-cel’s potential best-in-class profile and ability to transform the treatment landscape across neurologic autoimmune diseases," said Warner Biddle, CEO of Kyverna Therapeutics, in the press release. – Allison Whitten
Europe's drugmakers warn the region is losing the pharma investment race
Chairs of nine of Europe's largest drugmakers, including AstraZeneca, GSK, Novo, Novartis, Roche, and Sanofi, published an open letter this week warning that the region is losing the pharmaceutical investment race to the US and China. They urged the EU to speed up clinical trials, strengthen intellectual property protections, adopt pragmatic digital rules, and give member states fiscal room to spend more on health and innovative medicines, while stressing that the decisive levers sit with national governments. The numbers behind the alarm are stark: About 40 percent of new therapies never reach European patients, and those that do arrive after nearly 600 days. Europe's share of global pharma R&D has fallen from 43 percent in 1990 to 31 percent, its share of commercial clinical trials has halved to nine percent in a decade, and China has overtaken it in trials, patents, and new drug development. Europe spends about one percent of GDP on pharmaceuticals versus two percent in the US and 1.8 percent in China, and more than $600 billion in pharma investment has been announced across those two markets in the past two years. The chairs estimate that closing the clinical trial gap alone could unlock $70 billion and 82,000 jobs. – Andrea Corona
FDA panel backs GRAIL’s Galleri multi-cancer blood test
GRAIL’s Galleri multi-cancer early detection (MCED) test has received a mixed but favorable recommendation from an FDA advisory committee, which voted to support its safety, effectiveness, and overall benefit-risk profile in adults aged 50 years and older. The 10-member Molecular and Clinical Genetics Devices Panel voted unanimously that Galleri was safe, while six voted in favor and four against its effectiveness; the panel voted seven to two, with one abstention, that the test’s benefits outweigh its risks. Galleri analyzes cancer-specific methylation patterns in cell-free DNA from blood samples and is designed to detect more than 50 types of cancer, including cancers without recommended screening methods. However, several panelists questioned whether the available evidence demonstrates a clinical benefit, particularly whether detecting cancers earlier will ultimately reduce cancer deaths. The committee considered data from large studies including the 35,878-participant PATHFINDER 2 and the UK-based NHS-Galleri trial, which did not meet its primary endpoint of reducing combined stage 3 and 4 cancer diagnoses. The FDA is expected to make a final decision on GRAIL’s Premarket Approval application in the coming months and, if approved, Galleri would become the first FDA-approved MCED test. – Bree Foster
Acadia falls short in Phase 2 drug for Alzheimer’s disease psychosis, but will push ahead
Despite not hitting the primary endpoint of a significant improvement in Alzheimer’s disease hallucinations and delusions on a standardized scale, Acadia Pharmaceuticals announced in a press release that they still plan to move forward enrolling their Phase 3 program with once-daily remlifanserin, an oral small molecule 5-HT2A receptor inverse agonist. The company said they “narrowly missed” the primary endpoint and noted improvements over baseline scores compared to placebo that just barely missed significance, with a favorable safety profile. “This patient population has a significant need for an efficacious medication that is well tolerated, convenient to administer, and is compatible with the many concomitant medications commonly used by patients with Alzheimer’s disease. In particular, avoiding negative impacts on motor symptoms and cognition is encouraging, and such a medicine could be an important treatment option for patients,” said Jeffrey Cummings, Director of the Chambers-Grundy Center for Transformative Neuroscience, University of Nevada, Las Vegas, in the press release. – Allison Whitten
FDA nominee Overton sidesteps vaccine pressure at Senate hearing
Heidi Overton, a physician and White House domestic policy adviser nominated to lead the FDA, told senators at her confirmation hearing this week that she would "follow the law" on vaccines and mifepristone if pressured by the White House to change longstanding policy. Pressed by HELP Committee Chair Bill Cassidy, whose vote is key on a 12-11 panel, Overton called the MMR vaccine safe and effective despite having praised Trump's August executive order to split it into three shots and trim the childhood immunization schedule. On mifepristone, which she once called "dangerous," she acknowledged the FDA found it meets safety and efficacy standards but declined to prejudge an ongoing review. Overton also pledged to push initiatives like Operation Trailblazer to speed early drug research and counter China's biotech rise. If confirmed, she would replace acting commissioner Kyle Diamantas, who took over after Martin Makary resigned in May following a tenure marked by layoffs, staff departures, and accusations of politicized decisions. – Andrea Corona
