Mixed Phase 2 and 3 results test rare disease and neurology therapies

Four recent readouts in rare disease and neurology have produced mixed evidence, with one Phase 3 failure, one Phase 3 success, and two programmes advancing toward later-stage testing.

On 11 August 2026, Mereo BioPharma and Sentynl Therapeutics announced an option and license agreement for alvelestat, an oral inhibitor of neutrophil elastase for the lung disease caused by alpha-1 antitrypsin deficiency. The deal, valued at up to $475 million, includes plans for a global Phase 3 trial that Mereo would lead. The decision rests on combined data from the randomized, double-blind, placebo-controlled Phase 2 ATALANTa and ASTRAEUS studies, which enrolled 161 participants. In the 240 mg twice-daily group, alvelestat suppressed serum neutrophil elastase activity by more than 90% and produced statistically significant reductions in Aα-Val360 and desmosine/isodesmosine. The 120 mg dose had no significant effect on those biomarkers. The most common adverse event was headache. The companies have not yet fixed the Phase 3 endpoints, and the biomarkers are not established regulatory surrogates. Alvelestat may slow further lung damage but cannot reverse established emphysema.

On 2 September 2026, Ultragenyx reported that the Phase 3 Aspire study of apazunersen (GTX-102) for Angelman syndrome did not meet its primary endpoint on the Bayley-4 cognitive raw score or its key secondary endpoint, net response on the Multidomain Responder Index. The randomized arms had similar baseline characteristics, and treated and control groups showed no efficacy differences on Bayley cognition or on the five MDRI components. The safety profile was consistent with earlier Phase 1/2 data. Ultragenyx said it will review the programme, make substantial cost reductions while continuing to support its commercial portfolio, including the recent approval of GENGLYCOS and potential approval of UX111, and reiterated a goal of profitability in 2027. Shares fell nearly 47% after the news, according to pharmaphorum. The publication also reported the result as a warning for Ionis's similarly acting antisense therapy obudanersen, which is in Phase 3. STAT described the failure as a significant blow to Ultragenyx's path to profitability.

On 22 September 2026, Otsuka and Ionis announced that the Phase 3 FUSION trial of ulefnersen met its primary endpoint in FUS-ALS. The global, randomized, double-blind, placebo-controlled trial included a 72-week double-blind period followed by an open-label extension. The primary endpoint was a joint-rank composite of death or permanent ventilation, rescue, and change in the ALS Functional Rating Scale-Revised through day 505. Ulefnersen showed statistically significant benefit versus placebo (P=0.0005). Secondary endpoints, including serum neurofilament light chain and a composite time-to-event measure, also favoured treatment, and the safety profile was described as favourable with mostly mild or moderate adverse events. The companies said they intend to discuss the FUSION results with the FDA and other health authorities and to seek expedited regulatory submission pathways. According to NeurologyLive, the trial offers the first placebo-controlled evidence that a genetically targeted therapy can benefit FUS-ALS, though full results are not yet peer reviewed. An estimated 0.6% of all ALS cases are FUS-ALS, but the subtype makes up 43% to 52% of pediatric and juvenile-onset disease and can progress to respiratory failure within one to two years.

On 30 September 2026, at the EADV Congress in Vienna, Amgen presented Phase II data for daxdilimab in discoid lupus erythematosus. The antibody, which targets ILT7, had a favourable safety and tolerability profile and significantly improved skin-related symptoms, according to the company. Amgen is preparing registrational studies for the drug, which it acquired in the Horizon purchase.

Across the four programmes, the results clarify the immediate regulatory paths but not long-term answers. Alvelestat and daxdilimab still need Phase 3 trials. Apazunersen's future is under review. Ulefnersen's positive topline result awaits full analysis and peer review. None of the sources establishes that any of these investigational therapies is approved, and the disclosures cannot support conclusions about benefit beyond the specific populations and endpoints studied.