OrphanPulse Wk 41: BridgeBio Won Priority Review for the First Oral Achondroplasia Drug
FDA accepted BridgeBio’s NDA for oral infigratinib in children with achondroplasia with Priority Review on 6 October, setting a 4 February 2027 decision on what would be the first approved oral therapy for the condition. Shionogi paid $2 billion for IntraBio and its pipeline of rare neurology labels, and FDA extended its review of Novo Nordisk’s haemophilia A drug denecimig over manufacturing remediation. Ultragenyx sold a priority review voucher for $210 million and plans to sell a second.
placebo, PROPEL 3
IntraBio
voucher sale
NeuroPulse
BridgeBio won Priority Review for oral infigratinib in achondroplasia, with a decision due 4 February 2027
FDA accepted BridgeBio Pharma’s (Nasdaq: BBIO) NDA for oral infigratinib, a small-molecule FGFR3 inhibitor, for children with achondroplasia, with Priority Review and a PDUFA target action date of 4 February 2027, the company said on 6 October. If approved, it would be the first oral therapy for the condition. BridgeBio plans an EMA marketing application in Q4 2026 and says it is prepared to launch in the US on approval.
The filing rests on PROPEL 3, published in the New England Journal of Medicine. At Week 52, annualised height velocity improved by a least-squares mean of 1.74 cm a year over placebo (mean difference 2.10 cm a year, p<0.0001), and height Z-score was also significant (p<0.0001). BridgeBio reports no discontinuations or serious adverse events related to study drug. Infigratinib holds Breakthrough Therapy, Orphan Drug, Fast Track and Rare Pediatric Disease designations.
BioMarin’s daily Voxzogo (vosoritide) has been on the market since 2021, and Ascendis’ once-weekly Yuviwel (navepegritide) was approved in March 2026. Infigratinib’s argument is a pill against two injections, backed by what BridgeBio calls the largest height-velocity effect of any Phase 3 in the condition.
- Compare the right number. The headline +2.10 cm a year is the arithmetic mean difference; the least-squares mean, the figure usually compared across trials, is +1.74.
- Proportionality is the next commercial argument. Arm span Z-score improved by 0.37 SD (p<0.0001), and exploratory trends favoured infigratinib on sleep apnoea and otitis media, the complications families raise beyond height.
- The label age is not yet public. The release says children without an age range, and an exploratory analysis covered under-8s. The label decides how much of the injectable market infigratinib can contest.
- Oral competition is already building. Abbisko’s oral FGFR2/3 inhibitor added 2.4 cm a year in seven children at its lowest dose, as covered in OrphanPulse Week 39, so a first-to-market oral position may not stay exclusive for long.
Shionogi paid $2 billion for IntraBio, about 29 times Aqneursa’s 2025 sales
Shionogi agreed on 5 October to acquire IntraBio for $2 billion, taking Aqneursa (levacetylleucine), approved in the US and EU for Niemann-Pick disease type C and, since September, in the US for ataxia in ataxia-telangiectasia. IB1001 is also in clinical programmes in CACNA1A-related disorders, GM2 gangliosidosis and spinocerebellar ataxias. Fierce Pharma, working from Shionogi’s disclosures, puts IntraBio’s 2025 sales at around $68 million. Closing is expected between November and December 2026.
The price is for the labels still to come. Shionogi is buying a molecule that keeps collecting rare neurology labels, and it bolts onto the rare disease unit Shionogi built around Radicava, bought from Tanabe Pharma for $2.5 billion in April.
- The A-T label is weeks old. It rested on a 73-patient crossover study, as covered in NeuroPulse Week 38.
- CACNA1A is the next test. IB1001-304 was due to complete enrolment in October, in disorders Fierce Pharma puts at about 30,000 US patients.
- NPC is filling up. Two drugs are approved, and Rafael plans an NDA for Trappsol Cyclo after missing its pivotal primary, as covered in Week 40. The deal terms are in DealPulse Signal Week 41.
FDA extended its review of Novo Nordisk’s denecimig over remediation at a manufacturing facility
Novo Nordisk said on 5 October that FDA had extended its review of the BLA for denecimig, a treatment for haemophilia A with or without inhibitors in adults and children, citing ongoing remediation at its manufacturing facility after a pre-license inspection. Novo had expected a decision in Q3 2026, and FDA has given no revised timeline. FDA has not identified deficiencies in the efficacy or safety data from the FRONTIER programme, and Novo still targets a US launch in the first half of 2027 with no change to its 2026 outlook.
FDA’s objection is about the facility, and the clinical data stand. That keeps the launch plan intact on paper, but a manufacturing fix has no fixed duration, and each month of delay leaves non-factor prophylaxis to Roche’s Hemlibra and the newer entrants.
- The problem is narrow. Novo says the feedback does not affect its marketed products, which confines the issue to denecimig’s supply chain.
- Competitors are moving into the channel. LUX Infusion said on 9 October that Qfitlia (fitusiran) is now available through its national network for patients aged 12 and older with haemophilia A or B, with or without inhibitors.
- Manufacturing is the week’s theme. Scholar Rock resubmitted its EU application for apitegromab after replacing a fill-finish site that failed GMP.
Stoke aligned with FDA on a Vineland-3 composite for zorevunersen’s NDA, with launch targeted for early 2028
Stoke Therapeutics said on 5 October that it had completed a meeting with FDA to align on the planned US NDA for zorevunersen in Dravet syndrome, using a multicomponent analysis of four Vineland-3 subdomains: expressive communication, receptive communication, interpersonal relationships and personal skills. The NDA will rest on the Phase 3 EMPEROR trial, whose primary endpoint is major motor seizure frequency at Week 28, with five years of Phase 1/2a and open-label extension data also discussed. Stoke expects the readout in Q3 2027, a completed submission in the second half of 2027 and a potential US launch in early 2028. It holds US, Canada and Mexico rights, and Biogen has the rest of the world.
Stoke is asking FDA to weigh development alongside seizures, the claim a disease-modifying antisense drug needs to separate itself from anti-seizure medicines. The CEO described FDA as showing willingness to accept the Vineland approach; the release lists no formal agreement.
- On seizures alone the field is crowded. Fenfluramine, stiripentol and cannabidiol are approved in Dravet syndrome, so a label limited to seizure frequency would put zorevunersen among several options.
- Data go in before the readout. Stoke plans to submit data throughout the first half of 2027, which shortens the gap between topline and a complete filing.
- The designations stack up. Breakthrough Therapy in the US and China, orphan status in the US and EU, and Rare Pediatric Disease designation.
Pharvaris published RAPIDe-3 in The Lancet ahead of an April 2027 decision on the first oral B2 receptor antagonist
Pharvaris published Phase 3 RAPIDe-3 results in The Lancet on 8 October for oral deucrictibant 20 mg as on-demand treatment of hereditary angioedema attacks in adolescents and adults. The crossover trial met its primary endpoint and all 11 secondary endpoints, with time to onset of symptom relief of 1.28 hours and complete resolution at 11.95 hours, and most attacks were controlled with a single capsule. The NDA has a PDUFA date of 23 April 2027, and an EU application is under review.
On-demand HAE treatment is moving to pills. KalVista’s sebetralstat is already approved as an oral on-demand option, so deucrictibant arrives second with a different mechanism: it blocks the bradykinin B2 receptor that icatibant targets by injection.
- Subgroups widen the label case. Results were consistent across HAE types, including HAE with normal C1 inhibitor, and in non-severe laryngeal attacks.
- The placebo times are missing from the release. Pharvaris gave its own times without the placebo comparison, so the size of the benefit waits on the paper’s tables.
- Peer review lands six months before the decision. Prescribers will have the Lancet data well ahead of an April launch.
CSL paid $355 million upfront for lixudebart and left Alentis 45% of global profits
Alentis Therapeutics granted CSL exclusive worldwide rights on 5 October to co-develop and co-commercialise lixudebart, a claudin-1 antibody for rare kidney and liver diseases, now in the Phase II RENAL trial in ANCA-associated vasculitis with rapidly progressive glomerulonephritis. Alentis receives $355 million upfront, up to $1.2 billion in commercial milestones and 45% of global profits. According to Capital.com, development is also planned in focal segmental glomerulosclerosis and primary sclerosing cholangitis, neither of which has an approved therapy.
The disclosed milestones are all commercial, so Alentis is paid for the development risk it keeps through its profit share. CSL committed 23% of the $1.56 billion headline at signing, the largest licensing upfront of the week, as covered in DealPulse Signal Week 41.
- RENAL sets the timetable. With no development milestones disclosed, the Phase II readout is the next value event for both partners.
- One antibody, several fibrotic diseases. Lixudebart received FDA orphan designation in idiopathic pulmonary fibrosis in 2024, per Capital.com, alongside the kidney and liver plans.
- Two of the target diseases have nothing approved. FSGS and PSC are where a first therapy would face no incumbent.
Scholar Rock resubmitted apitegromab in Europe after swapping a fill-finish site that failed GMP
Scholar Rock resubmitted its EU marketing application for apitegromab in spinal muscular atrophy on 8 October, after withdrawing the first in August when the CHMP was informed of a lack of GMP compliance at the Catalent Indiana fill-finish facility. The new application uses an alternate US fill-finish site, and Scholar Rock expects a CHMP opinion in the first half of 2027. FDA approved the drug as Isembyld on 11 September for adults and children aged 2 and older already on an SMN2-targeted treatment.
The US approval and the European opinion are now separated by a manufacturing fix. In SAPPHIRE, motor function improved on apitegromab after a year while patients on SMN2 therapy alone lost function, and that is the benefit EU patients wait for.
- It targets muscle. Apitegromab blocks myostatin activation and is used alongside SMN2-targeted drugs.
- The site has a history. Observations at the same Catalent facility drew a US complete response letter in 2025, so moving fill-finish addresses a recurring problem.
- Global access is the stated plan. Scholar Rock cites more than 35,000 SMA patients globally and up to 50 countries.
Ultragenyx sold a priority review voucher for $210 million, keeps about $168 million after the NIH share, and has a second to sell
Ultragenyx agreed on 6 October to sell the rare pediatric disease priority review voucher awarded on 19 August with the approval of Genglycos (DTX401) for glycogen storage disease type Ia, for $210 million in cash at closing to an unnamed buyer, subject to Hart-Scott-Rodino clearance. Its 8-K discloses that a 2018 patent licence entitles the NIH to 20% of gross proceeds. Endpoints News reported that Ultragenyx plans to monetise a second voucher and called the sale one of the richest yet.
A voucher turns a small-population approval into cash before launch revenue arrives. Ultragenyx raises about $168 million without issuing stock, from a gene therapy for a disease with few patients.
- Licensed science takes a cut. The NIH’s 20% is a term to check in any programme built on in-licensed patents.
- The programme still pays. With FDA’s rare paediatric voucher programme extended to 2029, as covered in Week 40, sponsors such as BridgeBio can count a voucher in their approval economics.
- The buyer will surface later. A voucher is redeemed against a specific application, so the buyer usually emerges when it announces a priority review.
Endeavor’s taladegib met its Phase 2b primary in IPF, with 73% of patients on background therapy
Endeavor BioMedicines reported on 8 October that WHISTLE-PF, a 24-week Phase 2b trial of taladegib in 213 people with idiopathic pulmonary fibrosis at 74 sites in 14 countries, met its primary endpoint of a statistically significant improvement in percent predicted FVC against placebo. Total lung capacity and quantitative interstitial lung disease and fibrosis scores on high-resolution CT also improved significantly, and 73% of patients were on background standard of care. Taladegib holds FDA orphan designation and EMA orphan and PRIME designations.
The release gives no effect size, which is the number that decides whether a Hedgehog pathway inhibitor can join the approved antifibrotics. The release describes an improvement in lung function rather than slower decline, and that is the claim to check when the data are presented.
- Add-on matters. With most patients on background therapy, a positive result reads as additive benefit, the position any new IPF drug needs.
- Imaging moved too. Significant changes in quantitative fibrosis on HRCT support a structural effect alongside the functional one.
- Phase 3 talks start now. Endeavor is engaging regulators on Phase 3 plans, and PRIME gives it early EMA dialogue.
Rocket set a 12-patient pivotal design for its Danon gene therapy with FDA, with topline results due in mid-2028
Rocket Pharmaceuticals outlined on 6 October an FDA-aligned pivotal Phase 2 of RP-A501 in Danon disease: 12 male patients on commercial-grade product at a recalibrated dose, with success requiring at least seven to show both myocardial LAMP2 expression of Grade 1 or higher and a reduction of at least 10% in left ventricular mass index at 12 months. The co-primary endpoints are intended to support accelerated approval. The first three patients on the modified protocol showed no thrombotic microangiopathy or capillary leak syndrome in the initial observation period, and Rocket expects to finish dosing by mid-2027.
Seven of 12 is the bar, and Rocket’s Phase 1 met both criteria in all six patients at about 12 months. The lower dose and revised immunomodulation follow thrombotic microangiopathy and a fatal serious adverse reaction at the original dose, so the trial tests whether lower exposure keeps the effect.
- Durability supports the case. At three to seven years, LVMI stayed below baseline in five of six Phase 1 patients, with reductions of at least 10% in four.
- The population is modest. Rocket models about 10,000 to 11,000 US patients, including 4,000 males, and starts with symptomatic males with hypertrophic cardiomyopathy.
- The safety read is early. Rocket calls the modified-protocol observations preliminary, and follow-up continues.
Atsena’s XLRS gene therapy produced responses in six of nine patients at the Phase 3 dose and none of three controls
Atsena Therapeutics presented LIGHTHOUSE Parts A and B for ATSN-201 at the American Academy of Ophthalmology meeting, Fierce Biotech reported on 7 October. Half of 18 treated patients met microperimetry response criteria, the primary endpoint of the Phase 3 part, and at the Phase 3 dose six of nine responded against none of three untreated controls. Of eight patients at that dose with baseline acuity worse than 20/40, three reached 20/40 or better. Atsena plans to complete Phase 3 enrolment in Q1 2027, report in the first half of 2028 and file by the end of 2028.
Atsena chose its lowest dose for Phase 3, partly for tolerability. A two-thirds response rate at that dose against zero in a three-patient control arm is the signal, and the control arm’s size is the caveat.
- The field is open. X-linked retinoschisis has no approved therapy and affects about 30,000 men in North America and Europe, per Fierce Biotech.
- The endpoint is noisy. One patient responded in the untreated eye, which the Phase 3 control arm has to absorb.
- The money is in place. Bain Capital led a $150 million Series C.
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