OrphanPulse Wk 44: FDA Will Let One Licence Cover Patient-Specific Gene Edits, and CMS Is Widening Its Medicaid Deals
FDA issued draft guidance on 27 October that lets one biologics licence add new patient-specific gene edits without new trials, and CMS said its Medicaid outcomes-based model will extend beyond sickle cell disease. Inovio won accelerated approval for the first plasmid DNA immunotherapy, GSK and Hansoh’s B7-H3 ADC cut the risk of progression or death by 67% in relapsed osteosarcoma, and BioMarin and Idorsia placed new bets in Fabry disease. Egetis launched Emcitate in the US at about $950,000 a year.
in the CGT model
Ris-Rez
Emcitate
NeuroPulse
FDA will let one licence cover patient-specific gene edits, and CMS is taking its Medicaid gene therapy deals beyond sickle cell
FDA and CMS announced two steps on rare disease gene therapies on 27 October, as our 28 October Brief reported. FDA’s draft guidance on individualised genome editing lets a sponsor define an Individualized Feature Space, the limits within which its product may vary between patients. A new patient-specific variant inside those limits can then be added to the same biologics licence on assay data showing adequate safety and activity, without new clinical trials. It builds on the plausible mechanism framework FDA set out in February, which already allowed several mutations in one application.
Comments are open for 30 days after Federal Register publication, under docket FDA-2026-D-11783. CMS said its Cell and Gene Therapy Access Model, which negotiates outcomes-based agreements for state Medicaid programmes in sickle cell disease, will extend to diseases it has not yet named. The model has 34 participants (32 states, Washington DC and Puerto Rico) and two manufacturers, Vertex and Genetix Biotherapeutics, and a request for applications due in the coming months will also accept therapies already approved.
The licensing route is further along than the buying side. A developer can now plan one application for many bespoke edits, but no payer has said whether it will contract for a new variant that has no trial of its own. CMS’s first findings cite administrative burden and bargaining power, with no figures on patients treated.
- The disease list is the first signpost. The CMS request for applications will name the conditions it covers.
- Leadership has changed since February. The programme launched under Marty Makary and Vinay Prasad and now runs under Acting Commissioner Kyle Diamantas and CBER director Karim Mikhail, the Brief notes.
- Sickle cell set the template. Vertex and Genetix are the only manufacturers in the model so far.
FDA granted Inovio accelerated approval for Voceryq, the first plasmid DNA immunotherapy, after seven of 26 patients needed no surgery for a year
FDA granted accelerated approval on 30 October to Inovio Pharmaceuticals’ Voceryq (doruxapapogene ralaplasmid and lalikinogene sifuplasmid-gxfd), developed as INO-3107, for adults with recurrent respiratory papillomatosis. The basis was an open-label trial in 32 adults, with the frequency of surgeries to remove growths as an intermediate clinical endpoint. In the first year after treatment, seven of 26 patients who had needed at least three surgeries at baseline (27%) needed none, and Inovio must run post-approval trials to verify the benefit.
Precigen’s Papzimeos now has a rival. Papzimeos was approved in August 2025 and sold $74.7 million in the first half of 2026. Precigen shares fell 27% after hours on 30 October while Inovio’s rose more than 300%, Yahoo Finance reported.
- The headline uses a subset. FDA reported no complete response rate, and the 27% excludes six of the 32 treated.
- Electroporation comes with the drug. Its effects can include brief muscle contractions, bleeding at the injection site and lightheadedness, alongside injection-site reactions, headache and fatigue.
- Breakthrough and orphan designations backed the review, and CBER director Karim Mikhail called the approval “a meaningful scientific breakthrough”.
GSK and Hansoh’s B7-H3 ADC cut the risk of progression or death by 67% in relapsed osteosarcoma, in a 122-patient Chinese trial
Hansoh Pharma and GSK presented ARTEMIS-011 at ESMO 2026 on 26 October. The open-label Phase 3 at 24 sites in China randomised 122 patients aged 12 or older, whose osteosarcoma had progressed after at least two prior lines, 2:1 to risvutatug rezetecan (Ris-Rez) or gemcitabine plus docetaxel. Median progression-free survival by blinded central review was 5.5 months against 1.4 (HR 0.33, p<0.0001), disease control 76% against 33% and response 15% against 2.4%, OncLive reported.
The trial supports a filing in China, not yet elsewhere. GSK, which licensed rights outside China from Hansoh in December 2023 for $185 million upfront, plans its own Phase 2 in an international population, pharmaphorum reported. Osteosarcoma has seen few treatment improvements in decades.
- Toxicity is the trade. Grade 3 or higher treatment-related events reached 93% against 83%, serious treatment-related events 64% against 29%, and 71% needed dose reductions.
- Survival is immature. Ten patients died in each arm, for an HR of 0.51 with a confidence interval of 0.21 to 1.23.
- FDA granted Breakthrough Therapy designation in January 2025 for late-line relapsed or refractory osteosarcoma.
BioMarin paid $70 million for a subcutaneous Fabry enzyme, and Idorsia started Phase 3 of an oral rival with Nxera paying CHF 7 million
BioMarin licensed worldwide rights outside Korea to HM15421/GC1134A from GC Biopharma and Hanmi on 29 October: $70 million upfront, up to $405 million in milestones and tiered royalties for a long-acting enzyme given under the skin and now in Phase 1/2. A day earlier, Idorsia started two pivotal studies of lucerastat, an oral substrate reduction therapy: FAB-KLEAR, a kidney biopsy study in 16 men, and FAB-SWITCH, which compares lucerastat with enzyme replacement in 74 patients. Nxera paid CHF 7 million for rights in Japan and other Asia Pacific markets excluding China and will contribute to the Phase 3 costs.
Both bets reach for patients Galafold cannot treat. BioMarin, which bought Amicus and Galafold for about $4.8 billion in December 2025, framed the licence around patients without amenable mutations. Idorsia says lucerastat is designed to work regardless of enzyme activity, mutation or prior therapy, and expects to file as early as 2029.
- Lucerastat has missed before. The Phase 3 MODIFY study missed its primary endpoint on neuropathic pain, and the renal case rests on an open-label extension.
- BioMarin’s candidate could be the first subcutaneous ERT in Fabry and has held FDA orphan drug designation since 2024.
- Little was paid at signing. BioMarin’s $70 million is 15% of the $475 million headline.
Canada’s drug agency drafted a yes on Spinraza for adults with SMA, four years after it told provinces not to pay
As our 27 October Brief reported, Biogen Canada announced on 26 October that Canada’s Drug Agency had issued a draft recommendation to reimburse Spinraza (nusinersen) with conditions, for adults with type 2 and 3 SMA and for patients with two, three or four SMN2 copies. In July 2022 the committee said not to reimburse it in adults, finding no randomised evidence in treatment-naive adults. The review began in March 2026 under the agency’s pilot of reimbursement reassessments, feedback closed on 29 October and the final recommendation is due on 1 December.
The draft changes no coverage yet. The conditions are not public, and any price condition will surface in the final recommendation and the pan-Canadian Pharmaceutical Alliance negotiation that follows. Provinces then decide whether to fund.
- The 2022 price was C$118,000 a vial, or C$354,000 a year in maintenance and about C$708,000 in the first year, by the Brief’s estimate.
- Four SMN2 copies are new. The 2022 draft did not include them.
- Quebec already pays. It has reimbursed Spinraza for all SMA types and ages since 2018.
Egetis launched Emcitate in the US at about $950,000 a year, the first treatment for MCT8 deficiency
Egetis Therapeutics has launched Emcitate (tiratricol) in the US for peripheral thyrotoxicosis in adults and children with MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome, pharmaphorum reported on 28 October. FDA approved it in September, and Egetis launched earlier than it had predicted. The US list price is about $950,000 a year; in Germany, where it launched after EU approval, the list price is about €10,000 a month before discounts.
The US list price is about $950,000 a year against about €120,000 at German list price. Analysts put the eligible population at 5,000 to 10,000 across the US and Europe combined, so payers on both sides will see the gap.
- A priority review voucher is for sale. FDA awarded one with the approval, and Egetis hopes to sell it before the end of 2026; recent comparable deals were valued at $150 million to $220 million.
- Analysts see $300 million to $500 million a year in potential sales for Egetis’s first product.
- Support runs through Egetis RareLink, its patient programme with PANTHERx Rare Pharmacy.
NICE backed Arrowhead’s plozasiran eight days after UK authorisation, as a cost match for 57 to 114 people in England
As our 28 October Brief reported, Arrowhead announced on 27 October that NICE recommends Redemplo (plozasiran) for adults with genetically confirmed familial chylomicronaemia syndrome when diet and conventional triglyceride-lowering treatment have not worked well enough. The MHRA authorised it on 19 October through the International Recognition Procedure. NICE appraised it as a cost comparison under a standard technology appraisal, after the topic failed two of the highly specialised technologies criteria, and the price is confidential.
A cost comparison means Arrowhead accepted a price no higher than a treatment NICE already funds. The APOC3 drugs now compete under a shared ceiling, so dosing interval and eligibility will decide prescribing: plozasiran is injected every three months and Sobi’s olezarsen monthly.
- The trial result was large. Median fasting triglycerides fell 80% at month 10 against 17% on placebo in 75 patients.
- No pancreatitis-risk condition. NICE did not attach the high pancreatitis-risk restriction it placed on volanesorsen in 2020.
- Severe hypertriglyceridaemia is next. Arrowhead plans a US filing before the end of 2026, and Sobi received a CHMP opinion for olezarsen on 16 October.
FDA set a 28 February 2027 date for Palvella’s topical rapamycin, in a condition with no approved treatment
Palvella Therapeutics said on 28 October that FDA had accepted its NDA for QTORIN 3.9% rapamycin anhydrous gel in microcystic lymphatic malformations, with priority review and a PDUFA date of 28 February 2027. In the Phase 3 SELVA trial, 95% of participants aged six and older who completed the efficacy period improved on the mLM-IGA primary endpoint, and all six prespecified efficacy endpoints were significant (p<0.001). There are no FDA-approved treatments for the estimated 30,000 or more people with the condition in the US.
Low systemic exposure is the safety case. Blood rapamycin stayed below 2 ng/mL at every timepoint, with no drug-related serious adverse events.
- The response rate has no denominator yet. The release gives 95% of completers without the number enrolled.
- Breakthrough, Fast Track and orphan designations back the filing, and FDA’s Office of Orphan Products Development funded part of the programme.
- More indications follow. QTORIN rapamycin is also in development for cutaneous venous malformations and clinically significant angiokeratomas.
FDA pushed Agios’s mitapivat decision in sickle cell to 1 February 2027 while it weighs whether a REMS is needed
Agios said on 30 October that FDA had extended the review of its sNDA for mitapivat in sickle cell disease by three months, from 1 November 2026 to 1 February 2027. FDA asked on 9 October for information to judge whether a risk evaluation and mitigation strategy is necessary. Agios sent about nine months of updated safety data from the RISE UP open-label extensions on 19 October, and FDA classed the response as a major amendment on 28 October.
A REMS would shape the launch more than the delay. Agios says it is launch-ready and still discussing labelling, including possible REMS elements, for what it calls the largest indication it has pursued for mitapivat.
- RISE UP randomised 207 participants 2:1 to mitapivat 100 mg twice daily or placebo; the release repeats no efficacy figures.
- Mitapivat is already approved twice, as Pyrukynd in pyruvate kinase deficiency in 2022 and as Aqvesme in alpha- or beta-thalassaemia in 2025.
- No sickle cell brand name has been given.
Geron stopped its Phase 3 of imetelstat in myelofibrosis after monitors said it was unlikely to show a survival benefit
Geron said on 28 October that it is discontinuing IMpactMF after the independent Data Monitoring Committee advised that the trial was unlikely to meet its primary endpoint of overall survival. The open-label Phase 3 randomised 327 patients with intermediate-2 or high-risk myelofibrosis, relapsed on or refractory to a JAK inhibitor, 2:1 to imetelstat 9.4 mg/kg every three weeks or best available therapy. There were no new safety signals, and Geron will share a detailed analysis later.
Geron is now a one-indication company. Rytelo stays approved in the US and EU for certain patients with lower-risk MDS, and Geron says it will grow US demand and widen access abroad. It gave no sales figures or cash runway.
- Survival was the bar. IMpactMF was designed to show longer overall survival rather than spleen or symptom response.
- The release does not say whether a formal futility analysis was run.
- Q3 results are due on 4 November, the first chance to see Rytelo sales and cash after the decision.
Korea will cover Oxlumo and adult Crysvita from November, and approved a Hunter syndrome enzyme given into the brain
Korea’s Ministry of Health and Welfare said on 30 October that five drugs for rare and hard-to-treat diseases will be covered from November, Korea Biomedical Review reported. They include Oxlumo for primary hyperoxaluria type 1, which affects one to three people per million, and Crysvita, whose coverage extends from children to adults with hypophosphataemic rickets and osteomalacia. The same day GC Biopharma said the MFDS had approved Hunterase ICV (idursulfase beta), given into the brain’s ventricles alongside the intravenous form, for Hunter syndrome patients with central nervous system symptoms.
Crysvita’s extension removes a cliff at adulthood. Coverage stopped at childhood, so some patients stopped treatment as adults and those with adult-onset symptoms had no access. Rare disease patients pay 10% of covered costs, and the ministry gave no prices.
- Transplant was the main option for PH1 beyond symptom management before Oxlumo, the article notes.
- Hunterase ICV is approved in Japan, Russia, Peru and Taiwan, and a Korean extension trial has followed patients for at least four years.
- About two-thirds of Hunter syndrome patients have severe CNS damage, which the intravenous enzyme cannot reach, GC Biopharma says.
- The package also covers Xcopri and Spravato, covered in NeuroPulse this week, and Servier’s Tibsovo in IDH1-mutant bile duct cancer.
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