NeuroPulse Wk 42: Arrowhead Cut Tau by 73% With a Shot Under the Skin
Arrowhead’s ARO-MAPT cut cerebrospinal fluid tau by a mean 73% in healthy volunteers, 90 days after the last of two subcutaneous doses, the company’s first clinical evidence that its RNAi platform reaches the brain from under the skin. Vanda’s VQW-765 missed its Phase 3 primary in social anxiety disorder, and Banner randomised the first participant in a prevention trial combining donanemab with Roche’s oral nivagacetor. UCB won FDA approval for a Zilbrysq autoinjector, and Takeda launched oveporexton in Japan and China ahead of the US.
ARO-MAPT top dose
failed Phase 3
prevention trial
OrphanPulse
Arrowhead’s subcutaneous RNAi cut spinal fluid tau by 73%, and the effect held 90 days after the last dose
Arrowhead Pharmaceuticals (Nasdaq: ARWR) reported interim Phase 1/2a data on 14 October for ARO-MAPT, an RNAi therapeutic given by subcutaneous injection that silences MAPT, the gene behind tau expression. In healthy volunteers, mean CSF total tau fell 40% at 2.1 mg/kg and 69% at 6.4 mg/kg, each given on days 1, 8 and 15, and 73% at 12.8 mg/kg given on days 1 and 15, all measured at Day 105. The largest individual reduction was 85%. Arrowhead says the result validates its TRiM platform for siRNA that crosses the blood-brain barrier after subcutaneous injection.
The study, AROMAPT-SC-1001, plans about 64 healthy volunteers and up to 48 people with early Alzheimer’s disease, with data from the Alzheimer’s cohorts expected in 2027. Arrowhead reported no serious adverse events, deaths or discontinuations; the most common events were injection-site reactions, bruising, upper respiratory infections, back pain and headache. Regulatory discussions are under way for studies in MAPT-associated frontotemporal dementia and progressive supranuclear palsy.
Day 105 falls 90 days after the final dose, so Arrowhead is making the case for a subcutaneous injection once every three months or less. Stifel’s James Condulis told BioPharma Dive the data look arguably better than other blood-brain barrier approaches, while cautioning that tau is not yet a proven Alzheimer’s target.
- The readout is a biomarker in healthy brains. Lower CSF tau shows the drug reaches its target; Arrowhead says effects on tangles, cognition, function and progression still have to be studied in patients.
- Most of the effect arrives by the middle dose. Three injections of 6.4 mg/kg reached a 69% mean reduction, against 73% for two injections of 12.8 mg/kg.
- Analysts read it as a platform result. BioSpace led on the view that Arrowhead’s blood-brain barrier technology is arguably better than others, and FTD and PSP studies are already in regulatory discussion.
- Tau has a difficult record. BioPharma Dive notes that several tau-targeting medicines have struggled to show clear benefit, which is the risk the 2027 Alzheimer’s data carry.
Vanda’s VQW-765 missed its Phase 3 primary in women with social anxiety disorder, the subgroup its Phase 2 had picked out
Vanda Pharmaceuticals said on 15 October that VQW-765, a partial agonist of the alpha 7 nicotinic acetylcholine receptor, did not significantly reduce self-reported distress against placebo during a standardised social stress test in female participants, the trial’s primary analysis population, BioSpace reported. The Phase 3, VP-VQW-765-3201, enrolled 546 adults with social anxiety disorder and elevated baseline anxiety, who took drug or placebo before giving a presentation to a panel. Vanda has put the programme on hold pending analysis of the full dataset. It licensed the drug, then called AQW051, from Novartis in a December 2014 settlement over Fanapt.
The Phase 3 was built on a subgroup. The Phase 2 published in July 2025 missed in its overall population and was significant only in women, so the confirmatory trial bet on that signal and lost. Oppenheimer described the result to BioSpace as a clean miss.
- The trial tested on-demand use. Its ClinicalTrials.gov record describes on-demand treatment, taken ahead of a stressful event.
- No effect sizes yet. Vanda gave no numbers for either sex, so the scale of the miss waits on the full analysis.
- The hold leaves questions open. Results in men and in the overall population have not been disclosed.
Banner randomised the first carrier in a prevention trial testing donanemab, Roche’s oral nivagacetor and the two combined
Banner Alzheimer’s Institute said on 15 October that the first participant had been randomised in a prevention trial in the Colombian PSEN1 E280A kindred, whose carriers are nearly certain to develop Alzheimer’s disease at an average age of 44. In the first part, about 200 cognitively unimpaired and mildly impaired carriers receive Eli Lilly’s donanemab to clear amyloid plaque as completely as possible. They are then randomised to less frequent donanemab, Roche’s investigational oral gamma secretase modulator nivagacetor, both, or placebo, with 40 non-carriers on placebo. The National Institute on Aging funds the study with a grant of about $74.5 million, Lilly and Roche donate drug, and the University of Antioquia and Massachusetts General Hospital are partners.
The trial asks what keeps amyloid away once an antibody has removed it. An oral maintenance drug after an antibody clearance phase is the treatment model the design tests, and two competing companies supplied the drugs.
- Genetic certainty makes prevention testable. Carriers develop the disease on a predictable timetable, so plaque return and other biological measures can be compared across arms.
- Key design details are not public. The release names no phase, duration or primary endpoint, describing aims of clearing plaque and comparing how well each arm prevents its return.
- The combination arm pairs rivals. A Lilly antibody and a Roche oral drug go into the same patients.
UCB won FDA approval for a once-daily Zilbrysq autoinjector, with launch set for the first quarter of 2027
UCB said on 16 October that FDA approved an autoinjector for self-administration of Zilbrysq (zilucoplan), its once-daily subcutaneous C5 inhibitor, for adults with anti-acetylcholine receptor antibody-positive generalised myasthenia gravis. Zilbrysq was already self-administered by prefilled syringe. Approval rests on DV0012, which showed bioequivalence between the two devices in 14 healthy volunteers, and DV0013, a Phase 3b in 31 people with gMG in which 99.8% of 449 autoinjector uses delivered the complete dose. In a human factors study of 100 patients, caregivers and clinicians, 90% completed an injection at the first attempt without training.
For a drug injected every day, the device is the patient’s experience of the product. The autoinjector delivers a pre-set dose when pressed to the skin, and UCB positions it as the first once-daily autoinjector option for adults with gMG in the US.
- Availability lags approval. UCB expects the autoinjector to be commercially available in Q1 2027.
- The tolerability data are small. Injection-site pain was the most common adverse event, in three of 31 patients (9.7%).
- The eligible population is unchanged. The approval covers the same AChR antibody-positive adults as the prefilled syringe and adds a second way to inject.
Takeda launched oveporexton in Japan and China while its US launch waits on DEA scheduling
Takeda said on 14 October that Orzeyful (oveporexton), its oral orexin 2 receptor agonist, is available in Japan for adults and in China for adults and adolescents aged 16 and older with narcolepsy type 1. Both approvals came within about a month of FDA’s approval for adults with NT1, and Takeda expects the US launch next month, once DEA scheduling is complete. Two Phase 3 trials published in the New England Journal of Medicine in 2026 showed improvements over placebo in wakefulness, sleepiness, cataplexy, severity and quality of life at 12 weeks, with p-values below 0.001.
Physicians in Japan and China can prescribe the first orexin agonist before US physicians can. Controlled-substance scheduling, a step that follows FDA approval, set the US date. Takeda presents the drug as treating the orexin deficiency behind NT1.
- The China label is broader. It includes adolescents from 16; the Japanese and US labels cover adults.
- Side effects follow the mechanism. Insomnia, urinary urgency and frequency, and excess saliva were the most common.
- The release gives effect directions, not sizes. Takeda cites p-values below 0.001 without the underlying differences.
Tortugas’ obuprazine beat placebo by 16.7 PANSS points at its lowest dose in a 363-patient Chinese Phase 2b
Tortugas Neuroscience reported on 12 October that obuprazine (TRTL-107), a dopamine D2/D3 partial agonist, 5-HT2A antagonist and 5-HT1A partial agonist, met its primary endpoint in a Phase 2b run by partner Hansoh Pharma in 363 Chinese adults with acute schizophrenia at 24 centres. At Day 42, PANSS total score fell 28.6 points at 1.5 to 3.0 mg against 11.9 on placebo, a difference of 16.7 (p<0.0001), and the 4.5 to 6.0 mg and 6.0 to 9.0 mg arms improved by 13.2 and 14.7 points over placebo. Discontinuations for adverse events were about 2.1% on obuprazine against 2.5% on placebo. The data were presented at ECNP 2026.
The lowest dose did best, and the trial carried an aripiprazole reference arm. Tortugas says obuprazine was numerically better than aripiprazole on several endpoints but gives no figures, so the comparison that matters most cannot yet be checked.
- The US path starts now. Tortugas holds rights outside Greater China and plans to file a US IND; no Phase 3 is announced.
- Key safety data are missing. The release reports no weight, extrapyramidal or prolactin results, the measures that separate antipsychotics in practice.
- Responses came early. Responder rates at the two lower doses exceeded placebo and aripiprazole from Day 14, with no percentages given.
Beren showed decade-long adrabetadex data a month before its 17 November FDA decision in Niemann-Pick type C
Beren Therapeutics presented four posters at the Child Neurology Society meeting in Montréal on 15 October for adrabetadex, a cyclodextrin-based therapy for Niemann-Pick disease type C. In 76 patients treated for up to 11 years, those with the lowest baseline NPC severity scores (n=29) had 100% survival at five years, and in 25 patients treated for at least five years, prompt and delayed starts were both associated with slower progression than published natural history. A case report followed two sisters with infantile-onset NPC through about 10 years of treatment; the younger, who started about 10 months after her first neurological symptoms, has kept minimal disease activity. FDA accepted the NDA for Priority Review in February 2026, with a PDUFA date of 17 November 2026.
The decision will rest on uncontrolled evidence. Beren itself describes these data as small, uncontrolled case reports and observational analyses, the kind of evidence base FDA’s new rare disease framework says it wants to judge more consistently.
- Earlier starts did better. Patients treated within a year of neurological onset showed less progression from baseline than later starters.
- Adrabetadex sits underneath the approved drugs. Beren reports that arimoclomol and levacetylleucine were often added after adrabetadex, not used in its place.
- The market is consolidating. Levacetylleucine’s owner, IntraBio, is being bought by Shionogi for $2 billion as the third NPC therapy reaches its decision, as covered in Week 41.
Eton licensed Libervant for $10 million upfront and plans an April 2027 launch, after Valtoco’s exclusivity ends
Aquestive Therapeutics granted Eton Pharmaceuticals exclusive US rights to Libervant, a diazepam buccal film for seizure clusters, on 14 October, and stays as manufacturer under a 20-year supply agreement. Libervant holds tentative FDA approval, with full approval for patients 12 and older expected after Valtoco’s orphan exclusivity expires on 10 January 2027, and a decision for ages 6 to 11 due on 29 March 2027. Eton expects commercial availability in April 2027. Aquestive receives $10 million upfront, up to $47.5 million in milestones and mid-teens royalties, as covered in DealPulse Signal Week 42.
A competitor’s exclusivity sets the launch date. Valtoco nasal spray holds orphan exclusivity until 10 January 2027, and Eton puts the US seizure rescue market above $450 million a year.
- Film against spray is the pitch. In Eton’s survey, 71% of 101 patients preferred film to nasal spray assuming equal efficacy, stated preferences that Eton itself distinguishes from clinical outcomes.
- Milestones follow the label. $10 million is due on first US sale, falling to $5 million if full approval for ages 2 to 5 has not arrived, and $2.5 million on approval for ages 6 to 11.
- Eton is building a neurology team for its first neurology product, alongside 11 commercial rare disease products.
People newly diagnosed with epilepsy were six times as likely to develop dementia before 65 in a French cohort
A study published in Neurology on 14 October, with Vincent Navarro of Sorbonne University as an author, linked epilepsy to young-onset dementia using national data from France and Sweden. In France, 12.5% of 11,360 people with young-onset dementia had an epilepsy diagnosis, against 1.2% of 113,600 matched controls. In a prospective French cohort aged 30 to 55, the 10-year rate of young-onset dementia was 2.2% after a new epilepsy diagnosis, 1.7% with existing epilepsy and 0.2% without, and after adjustment newly diagnosed people were six times as likely to develop it, News-Medical reported.
The absolute risk stays low: 2.2% over 10 years in the highest-risk group. The study shows an association and cannot establish cause, and it lacked detail on the type or cause of dementia.
- New diagnoses carry the signal. Existing epilepsy raised the risk by 74%; a new diagnosis raised it about sixfold.
- Sweden pointed the same way. A matched comparison of 16,433 people with young-onset dementia showed a similar pattern in epilepsy medication use.
- Generalisability is limited. Both countries are high-income with universal health care, which the authors flag.
NervGen dosed the first patient in a 150-person registrational Phase 3 of NVG-291 in chronic spinal cord injury
NervGen Pharma said on 12 October that it had dosed the first participant in RESTORE, a randomised, double-blind, placebo-controlled Phase 3 of NVG-291, a subcutaneous peptide targeting the inhibitory CSPG-PTPσ pathway. The trial will enrol about 150 adults with chronic cervical motor-incomplete injury one to 10 years after trauma, dosed daily for 12 weeks, with hand function on GRASSP Quantitative Prehension as the primary endpoint. NervGen expects enrolment to complete in the second half of 2027 and topline data in the first half of 2028.
The primary endpoint is a functional gain, hand function, measured in people injured up to 10 years earlier. NVG-291 holds FDA Fast Track and EMA orphan designation for spinal cord injury.
- Phase 2 numbers are absent. The release describes placebo-controlled functional improvements in CONNECT SCI without figures.
- Treatment is short. Twelve weeks of daily injections are followed by four weeks of observation.
- An extension adds data. Completers can enter a 12-week open-label extension.
Anavex cleared an IND for blarcamesine in Fragile X, its third open IND, on mouse data alone
Anavex Life Sciences said on 15 October that FDA had cleared its IND for blarcamesine (ANAVEX2-73), an oral drug that targets sigma-1 receptors, in Fragile X syndrome. ANAVEX2-73-FXS-001 is a randomised, double-blind, placebo-controlled, dose-ranging Phase 2a in about 60 adult men, focused on safety, tolerability and pharmacokinetics, with behavioural (ABC-FX) and cognitive (NIH Toolbox) secondary endpoints. Supporting data come from three studies in the Fmr1 knockout mouse, the latest showing dose-related improvement in EEG abnormalities after 14 days.
An open IND is permission to start, and this trial is built to establish safety and dose. Anavex now has open INDs in Alzheimer’s disease, Rett syndrome and Fragile X, and blarcamesine is not approved anywhere.
- The need is real. Fragile X has no FDA-approved treatment, and the National Fragile X Foundation estimates 38,000 to 87,000 affected people in the US.
- Adult men only. Paediatric and female data will need separate trials.
- Efficacy is secondary. Behaviour and cognition are secondary endpoints, so a positive readout would mostly settle dose.
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