NeuroPulse Wk 43: Roche’s MS Pill Cut Relapses by 55% and Is Under Priority Review
Roche’s fenebrutinib cut relapses by 55% against teriflunomide in pooled Phase III data at MSToronto2026, and FDA is reviewing it under priority review in both relapsing and primary progressive MS. Rapport’s epilepsy drug beat placebo in bipolar mania by 3.1 points, Alnylam lowered mutant huntingtin by up to 64% with one intrathecal dose, and FDA accepted Biohaven’s resubmission in spinocerebellar ataxia. ICER opened a review of Compass’s psilocybin, with a vote in May 2027.
fenebrutinib
placebo, RAP-219
in Q3
OrphanPulse
Roche’s fenebrutinib cut relapses by 55% against teriflunomide, and priority review could make it the first pill for primary progressive MS
Roche presented pooled Phase III data for fenebrutinib, its investigational oral BTK inhibitor, at MSToronto2026 on 21 October. Across FENhance 1 and 2 in relapsing MS, annualised relapse rate fell 55% against teriflunomide over 96 weeks (p<0.001), annual whole-brain volume loss fell 23% (p<0.001) and 12-week composite confirmed disability progression fell 16% (p=0.04). In a pooled analysis, 75% of patients on fenebrutinib showed no evidence of disease activity at nearly two years.
A late-breaking MRI analysis found slowly expanding lesion volume up to 30% lower in relapsing MS over 96 weeks and in primary progressive MS over 120 weeks (p<0.001), and accumulation of paramagnetic rim lesions 62% lower in relapsing MS against active comparators (p=0.001). FDA accepted the NDA in both forms of the disease under priority review, Genentech said on 29 September, and NeurologyLive reported that FENtrepid met noninferiority against Ocrevus in primary progressive MS (HR 0.88). No decision date has been given.
Roche is setting fenebrutinib against its own Ocrevus in primary progressive MS. FENtrepid showed noninferiority, not superiority, with a confidence interval that crossed 1, so the case is an oral alternative to an infusion, with the lesion data arguing for activity inside the central nervous system. Ocrevus has been the only approved disease-modifying therapy in primary progressive MS since 2017, NeurologyLive notes.
- The disability signal is the thinnest number. A 16% reduction at p=0.04 sits beside a 55% cut in relapses.
- Safety will shape the label. Liver enzyme elevations were more frequent than with ocrelizumab, a 2023 FDA hold followed two suspected drug-induced liver injuries, and Genentech acknowledged an imbalance in deaths across the three trials, NeurologyLive reported.
- The relapse figure is pooled. FENhance 1 and 2 reported cuts of 51.1% and 58.5% separately at topline.
- Ocrevus is still extending. Roche showed 90% of children relapse-free over two years in OPERETTA 2, after European approval in paediatric relapsing MS on 15 October.
Rapport’s epilepsy drug beat placebo by 3.1 points in bipolar mania, at the low end of what analysts call competitive
Rapport Therapeutics reported on 20 October that RAP-219, a negative allosteric modulator of TARPγ8-containing AMPA receptors, met its primary endpoint in a three-week inpatient Phase 2 in 253 adults with acute bipolar I mania. Young Mania Rating Scale scores fell 15.4 points on 0.75 mg once daily against 12.3 on placebo, a difference of 3.1 (p=0.045), and the CGI-BP severity score improved by 0.4 (p=0.024). Discontinuations for adverse events were 3.2% on drug against 0.8% on placebo, and agitation was the most common event, at 16.7% against 9.4%.
RAP-219 is an epilepsy asset first. FOCUS 1 and FOCUS 2, pivotal Phase 3 trials in focal onset seizures, are enrolling. Stifel told BioSpace the bipolar trial “just hits”, with 3.1 points at the low end of the three to four points it considers competitive.
- The market read it as a narrow win. Shares rose more than 25% before the open and were down about 2% once trading began, BioSpace reported.
- Phase 3 is a 2027 decision. Rapport plans an end-of-Phase 2 meeting with FDA in Q1 2027 and two Phase 3 trials from the second half.
- Tolerability held. There were no serious adverse events, and no orthostatic hypotension, akathisia or extrapyramidal symptoms over three weeks.
Alnylam’s intrathecal brezosiran cut mutant huntingtin by up to 64% after one dose, and a pivotal study is planned for 2027
Alnylam Pharmaceuticals reported initial Phase 1b data for brezosiran (ALN-HTT02) on 23 October at the EHDN Clinical Research Congress in Kraków. The intrathecal RNAi therapeutic, partnered with Regeneron, targets exon 1 of HTT mRNA to lower full-length mutant huntingtin and the shorter HTT1a fragment. In 48 participants across five single ascending dose cohorts, CSF mutant huntingtin fell in a dose-dependent way, by a mean 60% to 64% at month 3 in the highest dose evaluated, with a maximum individual reduction of 83%. Participants have been followed for up to 12 months, and a sixth cohort of 12 is still enrolling.
Alnylam is making the case for dosing twice a year. Durability after one injection underpins that schedule, and the open-label extension will dose every six months for up to 36 months.
- No inflammation signal so far. Alnylam reports no dose-dependent rises in CSF inflammatory markers, neurofilament light or ventricular volume.
- The next test is clinical. A placebo-controlled pivotal study planned for 2027, subject to regulatory alignment, will ask whether lowering huntingtin slows progression.
- Key numbers are missing. The release gives no total huntingtin or HTT1a percentages and no adverse event counts.
FDA accepted Biohaven’s resubmission for Vyglxia in spinocerebellar ataxia and will convene an advisory committee before a decision in early 2027
Biohaven disclosed in a regulatory filing on 22 October that FDA had accepted its refreshed application for Vyglxia (troriluzole) in spinocerebellar ataxia, a group of rare genetic disorders that damage balance, coordination and speech, BioPharma Dive reported. FDA rejected the drug in November 2025, finding the key experiment unconvincing in part because of its design. The resubmission adds new supportive analyses, an advisory committee will review the evidence, and Biohaven expects a decision in the first quarter of 2027. Shares rose about 25%.
The advisory committee is the signal. TD Cowen’s Tyler Van Buren said scheduling one substantially increases the probability of approval, while RBC’s Leonid Timashev said the odds depend on how far FDA’s new flexibility extends.
- It would be a first. No medicine is marketed for SCA, and earlier data suggested Vyglxia might slow progression by as much as 70%.
- Europe has already said no. Biohaven withdrew its European application after evaluators questioned the supportive evidence.
- The new analyses are not public. Biohaven has not described them, so the evidence the panel will weigh is still unknown.
Kyverna’s one-time CAR-T kept 24 of 26 stiff person syndrome patients off chronic immunotherapy at one year
Kyverna Therapeutics presented the full one-year dataset from KYSA-8 at MSToronto2026 on 21 October. In the single-arm registrational Phase 2, 26 adults received one dose of miv-cel, an autologous CD19 CAR-T with CD28 co-stimulation. Median improvement in the timed 25-foot walk was 46% at week 16, the primary endpoint, and 49% at one year (p<0.0001), and 20 of 26 kept an improvement of at least 20%. There was no high-grade cytokine release syndrome or ICANS; five patients had grade 3 or 4 neutropenia and three had serious treatment-related events, all resolved.
A single arm of 26 will carry the filing. Kyverna says the data strengthen its SPS BLA package but gives no submission date. SPS has no FDA-approved treatment and an estimated 6,000 diagnosed patients in the US.
- Function moved beyond the walk test. The six-minute walk improved by a median 119 metres at one year, against a 20-metre threshold for meaningful change.
- Eight of 12 walking-aid users no longer needed one, a small subgroup.
- SPS is the lead, not the limit. Miv-cel holds RMAT designations in SPS, generalised myasthenia gravis and non-active secondary progressive MS, with a registrational trial running in gMG.
Clene filed CNM-Au8 for accelerated approval in ALS on neurofilament light, after two trials missed their primary endpoints
Clene said on 19 October that it had submitted an NDA for CNM-Au8, an oral gold nanocrystal suspension, seeking accelerated approval in ALS on reductions in plasma neurofilament light chain as a reasonably likely surrogate, NeurologyLive reported. The Phase 2 RESCUE-ALS missed its primary endpoint (p=0.43), and the HEALEY ALS platform trial missed its primary outcome (rate ratio 0.97). Clene’s case rests on open-label extensions: in HEALEY, plasma NfL fell 16% at 76 weeks (p=0.023) and estimated long-term mortality risk fell about 60% (HR 0.40).
FDA agreed the package could support a filing, not that it supports approval. Type C minutes in May 2026 said the data may support submission and review with NfL as a reasonably likely surrogate, after FDA called an earlier package insufficient in early 2024.
- Tofersen is the precedent. FDA approved Qalsody in April 2023 for SOD1 ALS on the basis of NfL reduction.
- The survival signals are uncontrolled. Both come from open-label extensions and comparisons with external controls, not randomised arms.
- A confirmatory Phase 3 starts in Q1 2027, and no review timeline or PDUFA date has been given.
argenx sold $1.7 billion of Vyvgart in a quarter as China approved a rival FcRn blocker from Harbour BioMed and CSPC
argenx reported third-quarter global Vyvgart net sales of $1.7 billion on 22 October, up 54% year on year, and FDA priority review for Vyvgart and Vyvgart Hytrulo in paediatric gMG, with a target action date in February 2027. The same day, China’s NMPA approved Harbour BioMed’s subcutaneous batoclimab for adults with AChR antibody-positive gMG. In the Chinese Phase 3, 58.2% of patients on batoclimab had sustained MG-ADL improvement in the first cycle against 31.3% on placebo (p=0.001), and CSPC’s NBP Pharma holds Greater China commercial rights.
Chinese payers now have a domestic FcRn comparator. Harbour calls batoclimab the first anti-FcRn therapy to complete its full clinical development for gMG in China, a company claim, and it reaches the market through a CSPC subsidiary with Harbour taking tiered royalties.
- Oedema and albumin are the trade-off. Peripheral oedema affected 38.8% on batoclimab against 4.6% on placebo, and plasma albumin fell during treatment and recovered afterwards.
- argenx is widening the label. An IMNM filing for Vyvgart Hytrulo is due by year-end, and empasiprubart’s Phase 3 in MMN reads out in December.
- Batoclimab comes in cycles: 680 mg weekly for six weeks, then four weeks off.
ICER opened a review of Compass’s psilocybin for treatment-resistant depression, with a public vote in May 2027
The Institute for Clinical and Economic Review posted a draft scoping document on 21 October for COMP360, Compass Pathways’ synthetic psilocybin, in treatment-resistant depression. Comments close at 5 pm ET on 10 November, a revised scope is due on or about 18 November, and the New England CEPAC will deliberate and vote at a public meeting in May 2027. ICER spent five weeks consulting the manufacturer, patient groups and clinicians before posting, and the report will include a section on reducing low-value care.
The vote may come after FDA has acted. FDA granted Compass a rolling NDA review in April 2026 and a Commissioner’s National Priority Voucher, which promises a one to two month review once the application is filed, so ICER’s benchmark could follow approval rather than precede it.
- Stakeholders have under three weeks. Written comments are capped at three pages and due by 10 November.
- Low-value care is in scope. ICER is inviting examples of low-value practices for a dedicated section of the report.
- Compass has not published effect sizes in its filing announcements. Its April release cited two positive Phase 3 trials without MADRS figures.
Cognition aligned with FDA on a nine-month registrational trial of zervimesine aimed at hallucinations and delusions in Lewy body dementia
Cognition Therapeutics said on 22 October that FDA had aligned with it on the design of a registrational study of zervimesine (CT1812), an oral small molecule, in mild to moderate dementia with Lewy bodies. Patients will be randomised to 100 mg once daily or placebo for nine months, with the NPI-2 score for hallucinations and delusions as the primary endpoint and ADCS-ADL as the key secondary. The company is completing the protocol and gave no start date or sample size.
The endpoint narrows the claim to psychosis. Cognition describes Phase 2 SHIMMER as slowing progression across neuropsychiatric, cognitive, motor and functional symptoms, but the registrational trial will be judged on hallucinations and delusions, which it says affect most people with DLB.
- No Phase 2 numbers in the release. Cognition gives no SHIMMER effect sizes.
- Grants have carried the programme. The company cites nearly $200 million in NIH and foundation funding.
- One trial, for now. The release refers to a single planned registrational study and does not say whether FDA will want a second.
The UK wants 92% of dementia referrals diagnosed within 18 weeks by 2029, up from about 60%, and is paying to test nine technologies
As our 20 October Brief reported, UK Research and Innovation is funding up to £80 million of real-world NHS testing under the NHS Fit for the Future Dementia Challenge it announced on 2 October, with money released against milestones. Evaluations start in January 2027 and run for up to two years, and technologies must be deployable in the NHS from 2029. Named projects include a blood biomarker panel from the University of Oxford and Dementias Platform UK, faster MRI from UCL, a 15-minute remote cognitive test from Cognitron, Imperial’s Minder home monitoring and an AI decision-support tool from Cambridge.
Britain is funding the front of the pathway before it has settled treatment access. An 18-week target turns a waiting-time figure into a procurement brief for diagnostics that hold UK clearance and can scale from 2029.
- Diagnostics firms and early Alzheimer’s drug makers are most exposed, the Brief found.
- Dementia caused over 72,000 UK deaths in 2025, almost one in eight.
- Commercial agreements are due this autumn and clinical protocols by the end of 2026.
Bioxodes reported slower oedema growth after brain haemorrhage with BIOX-101, from 17 treated patients and six controls
Bioxodes presented its Phase 2a BIRCH trial as a late-breaker at the World Stroke Congress in Seoul, announced on 21 October. Twenty-three patients with spontaneous intracerebral haemorrhage were randomised 3:1, open-label, to a 48-hour infusion of BIOX-101, which inhibits factor XI and XII activity, plus standard care, or standard care alone. The primary objective, safety, was met, with no treatment-related serious events and no secondary haemorrhage on day 7 MRI. In baseline-adjusted exploratory analyses, perihaematomal oedema grew 49.7% at 72 hours against 128.8% (p=0.0098), and haematoma volume fell 1.9% against a 25.5% rise (p=0.0097).
The control arm is six patients, and the arms were not balanced. Baseline haematoma was 25.3 mL against 14.1 mL and oedema 22.1 mL against 7.9 mL, which is why Bioxodes leans on adjusted analyses. The sample is too small to size the effect.
- No deaths in either arm, and a trend toward lower disability on mRS from day 7 to day 360 that was not significant.
- BIRCH 2 is the real test: a placebo-controlled global Phase 2b in about 230 patients, with oedema at 72 hours as the primary endpoint.
- It is not yet funded. Bioxodes says it is in discussions with partners and investors.
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