OrphanPulse Wk 42: Europe Backed Ascendis’ Weekly Achondroplasia Shot Ahead of the First Pill
The CHMP recommended Ascendis’ once-weekly Yuviwel (navepegritide) for children with achondroplasia on 16 October, putting a weekly injection on course for a first EU launch in Germany in Q1 2027, against BioMarin’s daily Voxzogo and ahead of BridgeBio’s oral infigratinib. FDA launched a Rare Disease Framework Initiative with a public meeting on 28 October, and the CHMP confirmed its refusal of Omeros’ Yartemlea, a drug FDA approved in December 2025. Ultragenyx sold a second priority review voucher, for $203 million, a week after the first.
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The CHMP backed Ascendis’ once-weekly Yuviwel for achondroplasia, with a German launch planned for early 2027
Ascendis Pharma (Nasdaq: ASND) said on 16 October that the CHMP adopted a positive opinion recommending EU marketing authorisation for once-weekly TransCon CNP (navepegritide), to be sold as Yuviwel, for children with achondroplasia aged two and older whose epiphyses are not closed. Ascendis expects a European Commission decision in Q4 2026 and a first EU launch in Germany in Q1 2027. Yuviwel is an orphan medicine, and the EMA will review whether that designation can be maintained.
The application drew on three randomised, double-blind, placebo-controlled trials and up to three years of open-label extension data, with the pivotal ApproaCH trial published in JAMA Pediatrics. FDA granted Yuviwel accelerated approval in February 2026 for the same age group. The EMA’s highlights for its 12 to 15 October meeting list Yuviwel among six new medicines recommended.
Achondroplasia in Europe now has a daily injection on the market in BioMarin’s Voxzogo and a weekly one recommended. BridgeBio’s oral infigratinib comes third: its US decision is due on 4 February 2027 and it planned an EMA application for Q4 2026, as covered in OrphanPulse Week 41.
- Orphan status is the open question. The EMA will review whether Yuviwel’s orphan designation can be maintained, a step that bears on market exclusivity in an indication Voxzogo entered first.
- Ascendis has a head start in Europe. Infigratinib’s EU application had not been filed as of BridgeBio’s 6 October update, so Yuviwel’s launch comes before any oral option can be reviewed there.
- The release gives no efficacy numbers. Height velocity results sit in the JAMA Pediatrics paper.
FDA launched a Rare Disease Framework Initiative, its answer to only 5% of rare conditions having an approved treatment
FDA announced the Rare Disease Framework Initiative on 14 October, a programme to build a fit-for-purpose review framework that accounts for each disease, the product type and the evidence realistically obtainable in small populations, set out in a white paper titled A New Framework for Rare Disease Review. The Rare Disease Innovation Hub leads it with CBER, CDER and the Office of the Commissioner, and it commits to clearer guidance, earlier patient input, external expertise and risk-based approaches to CMC review and pre-approval inspections. FDA holds a public meeting at White Oak on 28 October, facilitated by the Reagan-Udall Foundation, and Medical Daily reports comments are open through 11 December. FDA says only about 5% of rare conditions have an approved treatment.
The initiative promises consistency and leaves the hard rules to come. The Alliance for Regenerative Medicine told BioSpace that its success in cell and gene therapy depends on forthcoming guidance and rulemaking on single-arm trials and natural history data, the evidence questions behind uniQure’s AMT-130 and Capricor’s deramiocel.
- It systematises what exists. The white paper folds the Innovation Hub, CDER’s ARC programme and the RDEA endpoint pilot into a cross-centre approach, BioSpace reported.
- Manufacturing review gets explicit attention. Risk-based CMC review targets the step that held up Novo Nordisk’s denecimig, as covered in Week 41.
- It follows the plausible mechanism pathway introduced in November 2025, and Drug Discovery & Development counts it as FDA’s third rare disease policy change in just over a year.
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.
The CHMP confirmed its refusal of Omeros’ Yartemlea in TA-TMA, ten months after FDA approved it
Omeros said on 16 October that the CHMP had issued a negative opinion on narsoplimab, a MASP-2 antibody sold in the US as Yartemlea, after re-examining its June 2026 refusal for haematopoietic stem cell transplant-associated thrombotic microangiopathy, and the EMA’s meeting highlights list the refusal as confirmed. An eight-member ad hoc expert group convened for the re-examination recommended an external review of individual patient-level data, which Omeros says the CHMP did not provide to the group. FDA approved Yartemlea in December 2025 for patients aged two and older, and Omeros sells it with its own US field force.
The same evidence produced opposite decisions in the US and Europe. Omeros is ending its compassionate-use programme on rising US demand and will seek reimbursed named-patient access in Europe where permitted.
- The need is large for a rare disease. Omeros cites about 30,000 allogeneic transplants a year in the US and Europe, TA-TMA in up to 56% of recipients and mortality above 90% in severe cases.
- Partnering waits on approval. Omeros plans to license EU commercial rights only if marketing authorisation is granted.
- Infection risk is on the US label. Serious infections occurred in 36% (10 of 28) of trial patients treated with Yartemlea.
Regeneron’s Pasatru recorded no new bone lesions between weeks 56 and 84 in FOP, against nine on placebo
Regeneron reported 84-week OPTIMA data on 12 October for Pasatru (garetosmab-grts), its recently approved activin A antibody for adults with fibrodysplasia ossificans progressiva. The Phase 3 randomised 63 adults to 10 mg/kg or 3 mg/kg intravenously every four weeks or placebo, and its 56-week primary analysis, published in The Lancet, showed a reduction of 90% or more in new heterotopic ossification lesions. From week 56 to 84, the Pasatru arms developed no new lesions on CT against nine on placebo, and clinician-assessed flare-ups numbered one at 10 mg/kg, 14 at 3 mg/kg and 17 on placebo. Regeneron reported no deaths.
Infections rise with dose. Skin and soft tissue infections affected 78% at 10 mg/kg, 53% at 3 mg/kg and 33% on placebo, all resolved and none leading to discontinuation, so the higher dose buys flare control at a visible infection cost.
- The population is tiny. About 900 people are known to have been diagnosed with FOP worldwide.
- Europe and Japan are next. The EMA is reviewing a submission, and Japan has granted orphan designation ahead of filing.
- Children come later. OPTIMA 2, in adolescents and children, is due to start later this year.
Mirum’s Livmarli met its Phase 3 primary in ultra-rare cholestatic diseases and cut bile acids by 70% against 3.5% on placebo
Mirum Pharmaceuticals said on 12 October that EXPAND, a 20-week randomised, double-blind Phase 3 of maralixibat in 52 patients with ultra-rare cholestatic liver diseases including biliary atresia, met its primary endpoint. The average worst-daily ItchRO(Obs) score fell 1.81 points on maralixibat against 0.83 on placebo in children (difference 0.98, p=0.0004), and serum bile acids fell 70.1% against 3.5% in the overall population (p<0.0001). All five prespecified secondary endpoints were significant. Mirum plans an sNDA in the first half of 2027.
Biliary atresia is the subgroup to watch. In children with native livers, itch scores fell 2.16 points against 1.01 and bile acids 75.5% against 9.0%, a case for a population beyond Livmarli’s current Alagille and PFIC labels.
- Diarrhoea is the cost. It affected 64.0% on maralixibat against 11.1% on placebo, with one discontinuation for adverse events.
- The data are mostly paediatric. 46 of 52 patients were children, which shapes how far a label extends to adults.
- No new safety signals. There were no deaths, and Mirum reports no serious adverse events related to the drug.
Beacon’s laru-zova met the VISTA primary in XLRP, with 31% of high-dose patients gaining 15 letters against none untreated
Beacon Therapeutics released pivotal VISTA data on 12 October, after a late-breaking presentation at the American Academy of Ophthalmology on 10 October, for laruparetigene zovaparvovec (laru-zova), a gene therapy delivering the full RPGR ORF15 gene in X-linked retinitis pigmentosa. The Phase 2/3 randomised 85 males aged 12 to 48 to a high dose, a low dose or untreated control and met its FDA-endorsed primary endpoint on low-luminance visual acuity at Month 12. A gain of at least 15 letters occurred in 31.0% on the high dose (p=0.0019), 24.1% on the low dose (p=0.0106) and none of the controls, and a gain of at least 10 letters in 48.3%, 58.6% and 3.7%. Beacon plans to start a rolling BLA later this year.
The lower dose matched the higher on several measures. It produced more 10-letter responders, 58.6% against 48.3%, and the only significant microperimetry gain, 1.3 dB (p=0.0405) against 1.2 dB (p=0.0614), which leaves dose selection open as the BLA begins.
- The field is open. XLRP affects about 1 in 25,000 males in the US, Europe and Australia, and no treatment is approved.
- Designations are in place. RMAT, Fast Track, PRIME, ILAP and orphan designation in the US and EU.
- Safety tracked surgery. Two ocular serious adverse events, both in the low-dose group, were attributed to the procedure and resolved.
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.
Ultragenyx sold its second priority review voucher in a week for $203 million, taking voucher sales to $413 million
Ultragenyx agreed on 14 October to sell the rare pediatric disease priority review voucher awarded with the 17 September approval of Fayuvi (rebisufligene etisparvovec), its gene therapy for Sanfilippo syndrome type A, for $203 million to an unnamed buyer, Fierce Pharma reported. The sale follows the $210 million sale of the voucher from Genglycos a week earlier, for $413 million across the two. Finance chief Howard Horn called the proceeds meaningful non-dilutive funding. The EMA validated the company’s MAA for the same gene therapy on 2 October.
The second voucher sold for $7 million less than the first. No third-party share has been disclosed on this sale; the first carries a 20% NIH entitlement under a 2018 licence, as covered in Week 41.
- Two approvals, two vouchers. Genglycos in glycogen storage disease type Ia in August and Fayuvi in MPS IIIA in September each earned one.
- Europe is next for Fayuvi. The EMA has validated its MAA and given no timeline for a decision.
- Both buyers are unnamed. A voucher is redeemed against a specific application, so buyers usually surface when they announce a priority review.
Rezolute finished enrolling 16 patients in its Phase 3 in tumour hyperinsulinism, with seven of the first eight already responders
Rezolute said on 14 October that upLIFT, a single-arm, open-label registrational Phase 3 of ersodetug in hyperinsulinism caused by insulinomas and non-islet cell tumours, is fully enrolled at 16 participants. Patients receive 9 mg/kg weekly for eight weeks on top of standard care, and the primary endpoint is the share achieving at least a 50% reduction in glucose infusion rate. Of the first eight participants, seven met the responder criterion and fully stopped IV glucose; the eighth died of cancer progression about a week after enrolment and counts as a non-responder. Topline results are expected in mid-December 2026.
The bar is set in advance. With 16 participants, the lower bound of the 95% confidence interval must reach 30%, which requires a response rate of at least 56%, nine patients. With seven responders in hand, Rezolute needs two more from the remaining eight.
- Ersodetug acts at the receptor. The antibody binds the insulin receptor allosterically to blunt over-activation by insulin and related factors such as IGF-2.
- Congenital hyperinsulinism is the parallel track. Rezolute reported on 5 October that FDA recommended a pre-BLA meeting in that indication.
- Safety so far is clean. Rezolute reports no drug-related safety findings in the study.
OMass raised $310 million to take an MC2 receptor antagonist into Phase 2 in congenital adrenal hyperplasia
OMass Therapeutics closed an oversubscribed $310 million (£230 million) Series C on 15 October, co-led by Bain Capital Life Sciences, Forbion and Novo Holdings, all new investors. The money takes OMS1620, an MC2 receptor antagonist, through Phase 2 in congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome, and generates first clinical data for an SLC15A4 inhibitor in lupus. The release reports no clinical efficacy data.
OMass is blocking the receptor through which ACTH drives the adrenal gland. Endpoints framed the round as a challenge to Neurocrine and Vertex in CAH, and in the same week Neurocrine presented real-world evidence on the lifelong impact of classic CAH.
- Rising ACTH is the design problem. OMass built OMS1620 to maintain activity as endogenous ACTH levels rise.
- No timelines yet. The release gives no Phase 2 start or readout dates.
- The round is large for a Phase 2 start. Fierce Biotech described it as a milestone on OMass’ path to becoming Britain’s big biotech.
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