OrphanPulse Wk 43: Eight Months After FDA Said No, Disc’s Bitopertin Met Every Phase 3 Endpoint
Disc Medicine’s bitopertin met both co-primary endpoints and every secondary endpoint in the Phase 3 APOLLO trial in erythropoietic protoporphyria, eight months after FDA rejected it, and Disc raised $450 million to refile by year-end. FDA granted Ultomiris accelerated approval in IgA nephropathy as telitacicept matched atacicept’s two-year kidney data, and Merck KGaA, Alcon and Ambrose bought rare disease assets. Alnylam lowered mutant huntingtin by up to 64%, and FDA accepted Biohaven’s resubmission in spinocerebellar ataxia.
in light, bitopertin
Ultomiris in IgAN
after APOLLO
NeuroPulse
Disc’s bitopertin met every endpoint in Phase 3 eight months after FDA rejected it, and Disc raised $450 million to refile
Disc Medicine (Nasdaq: IRON) reported on 19 October that APOLLO, a randomised, double-blind Phase 3 in 183 adults and adolescents with erythropoietic protoporphyria or X-linked protoporphyria, met both co-primary endpoints. Over six months on 60 mg of oral bitopertin once daily, whole-blood protoporphyrin IX fell 41.4% more than on placebo (p<0.0001), and patients gained 12.2 hours a month in light without pain during month 6 (p=0.0010). Every secondary endpoint was significant, including fewer phototoxic reactions (p<0.0001).
FDA rejected the earlier application in a complete response letter disclosed on 13 February 2026, questioning whether a change in protoporphyrin IX it called relatively modest was a reasonable predictor of benefit, BioSpace reported. Disc plans to resubmit by the end of 2026 and expects a decision by mid-2027, and bitopertin holds a Commissioner’s National Priority Voucher that promises a one to two month review. On 20 October Disc priced an upsized $450 million offering at $75 a share, up from a proposed $350 million.
APOLLO answers FDA’s objection with a clinical endpoint. Time in light without pain now sits beside the biomarker FDA doubted, so the refiling no longer rests on protoporphyrin IX alone. Clinuvel’s Scenesse is the only FDA-approved treatment for EPP; bitopertin is a once-daily pill.
- Dizziness is the cost. It was the most common adverse event, in 50% of patients on bitopertin, mostly mild to moderate and transient, with no event above grade 3.
- The voucher may beat the guidance. CEO John Quisel told BioSpace FDA could act faster than mid-2027 under the voucher, though that is uncertain.
- Investors priced the redo. The offering was upsized by $100 million the day after the data.
- Roche is owed milestones. Disc licensed bitopertin from Roche in 2021 for an undisclosed upfront and more than $200 million in potential milestones.
Ultomiris won accelerated approval in IgA nephropathy on a 43.4% proteinuria cut, the first C5 inhibitor in the disease
AstraZeneca said on 21 October that FDA had granted accelerated approval to Ultomiris (ravulizumab) to reduce proteinuria in adults with primary IgA nephropathy at risk of progression. Approval rests on a prespecified week-34 interim analysis of the Phase 3 I CAN trial, designed to enrol about 510 adults in 28 countries, in which 24-hour UPCR fell 46.6% on ravulizumab against 5.6% on placebo, a placebo-adjusted 43.4% (p<0.0001). Continued approval depends on eGFR at week 106, and the drug keeps its boxed warning for meningococcal infection and its REMS.
Ultomiris enters on proteinuria alone. AstraZeneca says it has not been established whether ravulizumab slows kidney function decline, while Vera’s Trutakna, approved in July, now has two years of eGFR data behind it.
- Dosing is an infusion every eight weeks, after a weight-based loading dose and a second dose on day 15.
- The confirmatory readout is the trial’s final primary endpoint, change in eGFR at week 106.
- The safety programme carries over. The boxed warning and REMS apply as in its other indications.
Telitacicept held eGFR loss to 0.6 a year over two years in IgA nephropathy, the same slope as Vera’s atacicept, but only in a Chinese trial
Vor Bio presented final two-year results from RemeGen’s Phase 3 TELIGAN at ASN Kidney Week in Denver on 22 October. In 318 Chinese adults, eGFR declined by 0.6 mL/min/1.73 m² a year through week 104 on 240 mg of subcutaneous telitacicept against 5.7 on placebo, a difference of 5.1 (p<0.001), and the risk of a confirmed 30% eGFR decline fell 89% (HR 0.11). UPCR fell 60.3% against a 0.9% rise on placebo, and there were no composite kidney failure events on drug against five on placebo.
Two dual BAFF and APRIL blockers now show the same two-year slope. Vera reported atacicept at 0.6 a year against 5.6 on placebo in ORIGIN 3, presented in full at the same meeting and in NEJM. Vor Bio says it has not independently verified RemeGen’s data and has announced no IgAN Phase 3 outside China.
- China has already approved it. Telitacicept won conditional approval there in June 2026 for proteinuria in primary IgAN.
- Vor’s ex-China trials are elsewhere, in generalised myasthenia gravis and Sjögren’s disease.
- Injection-site reactions were common, at 56.0% against 18.9%, while serious adverse events were lower on drug, 8.2% against 18.2%.
- Otsuka also presented final VISIONARY results for Voyxact at the meeting; its two-year eGFR data were first reported in July.
Merck KGaA, Alcon and Ambrose bought rare disease assets in two days, led by $1.3 billion for Silence’s polycythaemia vera siRNA
Merck KGaA agreed on 19 October to pay $20 per ADS in cash for Silence Therapeutics, about $1.3 billion and a 130% premium, for divesiran, an siRNA for polycythaemia vera that produced responses in 88% of Phase 2 patients and goes into Phase 3 on 12-week dosing. Alcon is paying $550 million upfront, plus undisclosed commercial milestones, for Neurotech Pharmaceuticals and Encelto, approved in March 2025 as the only FDA-approved treatment for macular telangiectasia type 2. Ambrose Healthcare is buying AM-Pharma for up to €161 million (about $181 million) to develop ilofotase alfa in hypophosphatasia, as covered in DealPulse Signal Week 43.
Merck KGaA paid for a dosing advantage. Divesiran’s case against Takeda and Protagonist’s Mimrylo, a weekly injection approved in August 2026, rests on dosing every 12 weeks, Fierce Biotech reports.
- Alcon bought a defined market: about 25,000 US patients with MacTel and 2,000 to 3,000 new diagnoses a year, Neurotech estimates.
- AM-Pharma’s drug has a history. Pfizer took an $87.5 million minority stake and option in 2015 and walked away, and a Phase 3 in sepsis-associated kidney injury failed before the move into HPP, Fierce Biotech reports.
- Silence came from a competitive sale process, its interim principal executive officer Iain Ross said, after Merck KGaA agreed in June to buy Bio-Techne for more than $11 billion.
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.
FDA extended Orladeyo’s oral pellets to adults and adolescents, so the once-daily HAE pill no longer has to be swallowed whole
BioCryst said on 21 October that FDA approved its supplemental NDA for a 150 mg oral pellet formulation of Orladeyo (berotralstat) for prophylaxis of hereditary angioedema attacks in patients aged 12 and older. The pellets can be poured into the mouth and swallowed with water or milk, or sprinkled on soft food. Capsules were approved for this age group in December 2020 and pellets for children aged 2 to under 12 in December 2025; this approval rested on manufacturing data and safety and tolerability against the capsule.
Children can now stay on one formulation as they grow. BioCryst positions the pellets for patients who have difficulty swallowing, prefer not to take a capsule or want to stay on pellets beyond age 12.
- No new efficacy data were needed. The basis was manufacturing data and comparative tolerability.
- Price and launch timing were not given; BioCryst reports third-quarter results on 4 November.
- The label population is unchanged. The approval changes the form of the drug, not who can take it.
FDA lifted the hold on Aardvark’s ARD-101 in Prader-Willi syndrome, but the halted Phase 3 left only a modest, exploratory signal
Aardvark Therapeutics said FDA lifted the clinical hold on ARD-101, an oral bitter taste receptor agonist for hyperphagia in Prader-Willi syndrome, on 22 October. Aardvark reported one cardiac serious adverse event at 800 mg twice daily in a participant also taking pitolisant, which FDA agreed was related to a drug-drug interaction. The Phase 3 HERO trial was terminated early with 67 of 90 planned participants randomised, and ARD-101 showed a modest, exploratory reduction in HQ-CT hyperphagia scores at week two, with no magnitude or p-value given.
A lifted hold restarts the programme, not the evidence. CEO Tien Lee said the partial data are not sufficient to draw definitive conclusions, and Aardvark will ask FDA to align on a new Phase 3, resuming PWS trials in 2027 at a dose below 800 mg twice daily.
- The effect faded off drug. HQ-CT scores returned to near baseline after ARD-101 was stopped, with less rebound on placebo.
- The extension is uncontrolled. Patients switching from placebo to ARD-101 fell an average of 6 points on HQ-CT.
- No filing timetable. The release gives no NDA timing.
Samsung Bioepis will be Brazil’s sole eculizumab supplier for 10 years from 2027, for the health ministry’s costliest specialty medicine
Samsung Bioepis said on 20 October that it signed a 10-year agreement to supply SB12, its eculizumab biosimilar, to Brazil’s public health system from 2027 under the Productive Development Partnership framework, with Bahiafarma and Bionovis, Korea Biomedical Review reported. The consortium was selected as sole supplier; Samsung Bioepis will ship finished product, then transfer technology so the partners can take over manufacturing in Brazil. Public spending on eculizumab exceeded 947 million reais, about $171 million, in 2025.
Brazil is buying the biosimilar and the factory. PDP contracts guarantee public purchases in return for local technology transfer, so 10 years of exclusivity is the price of building domestic supply.
- Coverage is narrower than the label. SUS covers reference eculizumab only in PNH, while ANVISA approved SB12 in December 2024 for PNH and aHUS in adults and children.
- No contract value was disclosed, and no volumes or prices.
- Biologics dominate the bill. They make up about 12% of SUS medicine purchases and about 60% of government medicine spending.
Rgenta agreed a 150-patient, placebo-controlled Phase 3 with FDA for its oral MYB splicing modifier in adenoid cystic carcinoma
Rgenta Therapeutics said on 22 October that it had completed an end-of-Phase 2 meeting with FDA and aligned on a Phase 3 of RGT-61159, an oral small molecule that modulates splicing of the transcription factor MYB. About 150 patients with biomarker-selected, recurrent or metastatic adenoid cystic carcinoma will be randomised 2:2:1 to 84 mg or 60 mg once daily or placebo, all with best supportive care, with progression-free survival as the primary endpoint. Rgenta plans to start in Q1 2027.
Disease control is the signal, not shrinkage. In Phase 1a/b, 84.6% of 39 evaluable patients had disease control but only three had partial responses, which suits a placebo-controlled trial on progression-free survival.
- MYB drives the disease. Rgenta cites MYB overactivation in over 90% of cases and no effective targeted therapy for recurrent or metastatic disease.
- The population is small. About 11,000 people in the US and 200,000 worldwide live with ACC, per Rgenta.
- Two doses go forward, so the Phase 3 will also settle the dose.
INmune Bio filed its final pre-MAA package for ebstrocel in RDEB and targets UK approval in mid-2027, ahead of the US and Europe
INmune Bio said on 21 October that it had submitted its final pre-marketing authorisation package to the MHRA on 20 October for ebstrocel (CORDStrom), a pooled allogeneic therapy made from umbilical cord-derived mesenchymal stromal cells, in recessive dystrophic epidermolysis bullosa. It now plans a complete MAA in February 2027 instead of a rolling submission, which it says could bring UK approval forward by about six weeks, to mid-2027. The same day it signed Uniphar to build named-patient access in selected European and MENA markets, with no terms disclosed.
Britain first, then the US, then Europe. INmune is preparing a Type B meeting request with FDA ahead of a planned BLA in Q2 2027, and is prioritising that filing over an EMA submission.
- No efficacy numbers. The release refers to successful clinical readouts without figures.
- US designations are in place: Orphan Drug and Rare Pediatric Disease.
- The MHRA timing is the company’s estimate, which assumes a response three to six months after submission.
When a development gets big enough, it earns a full report.
Synopulse’s monthly intelligence lines: deep, single-subject reports on the moves that reshape a field.
Tracking this market more closely?
We prepare custom briefings on market access, pricing and deal activity, cut by therapy area, company or country.