Gene Editing Weekly — September 12–18, 2026: a first-in-disease gene therapy, a rolling IND pilot, and Cellectis's in vivo pivot
Fayuvi becomes the first approved treatment for Sanfilippo syndrome type A, the FDA opens a rolling IND pilot, and Cellectis, Prime Medicine and Serapha Bio stake their next steps on in vivo editing.
The coverage window for this issue is September 12–18, 2026, Eastern Time. The seven days hold one approval, one new pathway into first-in-human trials, guidance from three companies at a single investor conference, one pipeline pivot and two governance publications. The approval is the item most likely to be misread: the product adds a working gene copy, while the editing programs this channel follows change the genome's own sequence.
| Track | Primary change | Evidence boundary | Next milestone |
|---|---|---|---|
| Regulatory | The FDA granted full approval to Fayuvi (rebisufligene etisparvovec-hopf) on September 17 for pediatric patients with mucopolysaccharidosis type IIIA, also called Sanfilippo syndrome type A — the first approved treatment for the disease. 1 | A one-time AAV9 gene-addition therapy, supported by a single-arm study read against an external natural-history cohort; its mechanism is gene addition. 2 | Commercial product available to ship to qualified U.S. treatment centers within 30 to 60 days. 2 |
| Regulatory | The FDA launched the Expedited IND Pilot Program on September 15, under which sponsors pair with qualified research institutions and the agency reviews IND components on a rolling basis. 3 | A program design under the HHS initiative Operation TrialBlazer; no participants have been selected. 3 | Applications close October 30, 2026; the FDA expects to select 8 to 10 sponsor-institution pairs. 3 |
| Commercial | Vertex recorded $76.4 million of CASGEVY revenue in the second quarter of 2026, 78% above the first quarter and 151% above the year-ago quarter. 4 | Reported product revenue for the three months ended June 30; the figure and the patient-start pace were restated at a September conference and carry no new clinical data. 5 | CTX310 Phase 1b data in severe hypertriglyceridemia and CTX611 Phase 2 top-line data, both guided to year-end 2026. 5 |
| Clinical | Prime Medicine said its Wilson's disease Phase 1/II study is dosing patients across three initial cohorts and that proof-of-concept data are expected in 2027. 6 | Conference guidance; the company disclosed no new patient data. 6 | A regulatory filing for alpha-1 antitrypsin deficiency still guided to this quarter, with early clinical data in 2027. 6 |
| Corporate | Cellectis will exit the CAR-T candidates lasme-cel and eti-cel and rebuild around two in vivo editing programs. 7 | A board decision of September 11 supported by preclinical data; first human data are planned for 2027 and 2028. 7 | Initiation of a Phase 1 investigator-initiated trial in China for .HEAL-101, with preliminary data guided to the second half of 2027. 7 |
| Corporate | Serapha Bio named Kenneth T. Mills chief executive and appointed four other senior officers. 8 | Appointments; the underlying clinical evidence is an investigator-initiated trial presented at a respiratory congress this month. 8 | Completion of the Boundless Bio merger in the fourth quarter of 2026 and a Phase 2/3 start for SERP-01 in late 2026 or early 2027. 8 |
| Governance | The Lancet published an editorial on September 12 arguing that gene-editing therapies have to be delivered into patients safely for the field's promise to hold. 9 | Editorial opinion in a clinical journal, rather than a regulatory action. 9 | None scheduled. |
| Governance | Nature Biotechnology published a comment on September 15 on China's Decree 818, which governs hospital-based cell, gene and individualized therapies. 10 | Analysis of a named regulation by an outside author; the comment sets its own accountability conditions. 10 | Whether Chinese institutions report adverse outcomes under the decree. 10 |
| FDA ledger | CBER's "What's New for Biologics" listed the Fayuvi approval letter and a Vaccines and Related Biological Products Advisory Committee meeting for October 1 on 2027 Southern Hemisphere influenza strain selection. 11 | A weekly posting ledger; it records zero product-specific gene-editing actions for the window. 11 | The October 1 advisory committee session. 12 |
Regulatory
The FDA approves the first treatment for Sanfilippo syndrome type A
The FDA granted full approval to Fayuvi on September 17 for pediatric patients with mucopolysaccharidosis type IIIA, a lysosomal storage disease that strips children of cognitive, language and motor function and leads to death at a median age of about 15. 12 Fayuvi is a gene-addition product made by Ultragenyx: a single intravenous infusion of an AAV9 vector that carries a working copy of the SGSH gene, so that cells can produce the sulfamidase enzyme and break down heparan sulfate. 1 The vector adds a functioning gene copy, which makes this a gene-therapy approval.
Ultragenyx ran an open-label, single-arm study and compared 17 treated patients against 27 untreated patients from an external natural-history cohort, measuring the mean change in cognitive score on the Bayley-III scale between 24 and 60 months of age. Treated patients scored 23.5 points higher over the study period, with p<0.0001, and the company says follow-up now extends to nearly eight years. 2 The FDA's acting deputy director of the Office of Therapeutic Products, Megha Kaushal, described the result as showing that systemic AAV9 delivery "can reach the central nervous system at therapeutically relevant levels in pediatric patients." 1
The same comparison structure is where the agency has been moving. On the page announcing the IND pilot, the FDA points to its revised draft guidance on substantial evidence of effectiveness, which sets out how sponsors can support approval with one adequate and well-controlled pivotal investigation plus confirmatory evidence. 3 The agency's June draft guidance for genome-editing products approaches the same flexibility from the sponsor's side, telling developers to build on findings already established in the field. 13
The approval also carries the safety record that follow-on programs inherit. The FDA lists liver enzyme increases, vomiting, fever, reduced white-cell and platelet counts, and increased amylase among the common adverse reactions, and its warnings cover thrombotic microangiopathy and the long-term risk that AAV material integrates into the genome and contributes to a malignancy. 1 Patients receive corticosteroids from the day before infusion for at least eight weeks afterward. 1
Commercial terms landed the same day. Ultragenyx set a U.S. list price of $3.95 million, and executives said on the company's call that caring for a child with the disease over a lifetime can exceed $8 million. 14 J.P. Morgan analysts, as reported by Reuters, put peak worldwide sales at $200 million to $250 million, and Ultragenyx shares closed 12.6% higher. 14 The company also received a Priority Review Voucher, which it can sell or use on another application. 2
A rolling route into first-in-human trials
The FDA opened its Expedited IND Pilot Program on September 15 as part of Operation TrialBlazer, the HHS clinical-trial reform initiative. 3 Under the pilot, a drug sponsor partners with a qualified research institution that has the scientific expertise to help assemble the IND, and the FDA accepts and reviews individual components of the submission as they are completed rather than waiting for the whole package. 3 The pilot also encourages sponsors to run institutional review board review and site activation alongside IND development, which are the two steps that normally begin after clearance.
Alongside the pilot, the FDA updated its chemistry, manufacturing and controls guidance for Phase 1 INDs to spell out what is required at that stage, and said companies that submit only phase-appropriate data can save six to twelve months of development time. 3 It also published a Phase 1 IND Navigator page consolidating IND requirements in one place, opened a Phase 1 contact center for real-time questions, and issued a draft guidance on using quantitative systems pharmacology to set first-in-human doses. 3
Sponsors have until 11:59 p.m. Eastern Time on October 30, 2026 to apply, and the agency has said it expects to select 8 to 10 sponsor-institution pairs. 3 An applicant pairs with an institution that helps assemble the IND, which is the submission standing between a preclinical editing program and its first patient.
Clinical and corporate
CASGEVY's ramp, and what CRISPR Therapeutics has queued behind it
Vertex reported $76.4 million of CASGEVY revenue for the second quarter of 2026, up 78% from the first quarter and 151% from the second quarter of 2025, and first-half revenue of $119.3 million against $44.6 million a year earlier. 4 CASGEVY is the first approved CRISPR-Cas9 medicine, and its quarter-by-quarter shape is uneven because each treatment is a one-time therapy recorded when it is delivered.
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Vertex's own yardstick for the year is "$500 million or more in revenue from non-CF products," which covers CASGEVY together with the acute-pain drug JOURNAVX. 4 Vertex reported the first and third quarters of 2025 inside its half-year and nine-month totals; each is that total less the quarters reported within it, and the first quarter of 2026 is the half-year total less the second quarter. 1516
At Morgan Stanley's 24th Annual Global Healthcare Conference on September 14, CRISPR Therapeutics chief executive Sam Kulkarni put the operating numbers behind the revenue: more than 100 patients entering treatment per quarter, and a price of roughly $2 million per patient, which he said points to annual revenue "well north of half a billion dollars and getting closer to the billion-dollar mark." 5 The expansion of the CASGEVY label to children aged 2 and older adds about 5,500 potentially eligible patients, and Vertex has completed submissions in the United Kingdom and Saudi Arabia for ages 5 to 11. 4
The remaining constraint is time rather than manufacturing. Kulkarni said reimbursement, hospital contracts and prior authorizations are in place, and that the delay now sits in the patient's own path: exchange transfusions before cell collection add two to three months, and the full journey from initiation to treatment runs six to nine months or longer. 5 Vertex is developing gentler conditioning agents that would shorten the hospital stay from two or three weeks to three days or less, which would also open the therapy to patients with less severe disease. 5
Three programs carry the next round of catalysts, all guided to year-end 2026:
- CTX310, an ANGPTL3 knockout for severe hypertriglyceridemia, reported up to 80% target knockdown and near-50% reductions in LDL cholesterol and triglycerides in Phase 1a, and Phase 1b is dosing the highest Phase 1a dose.
- CTX611, a Factor XI siRNA partnered with Sirius Therapeutics, is in Phase 2 in total knee arthroplasty, where it tests prevention of venous thromboembolism.
- Zugo-cel, an allogeneic CAR-T, is in a basket trial across autoimmune indications. 5 On zugo-cel, Kulkarni said: "I think we have a lot more to see in terms of data before it becomes something real." 5 Data for CTX340 in refractory hypertension and for the alpha-1 antitrypsin program using the company's SyNTase editor are guided to early 2027.
Prime Medicine's platform meets its delivery ceiling
Prime Medicine used the same conference on September 16 to argue that its editors are more versatile than the alternatives and to concede where the field is stuck. 6 Chief executive Allan Reine said prime editing covers all twelve possible base-pair changes against four for base editing, uses a single-strand nick instead of a double-strand break, and writes larger inserts through its PASSIGE system. 6
Wilson's disease is the lead in vivo program. Prime Medicine received IND clearance in July and a clinical trial application clearance in New Zealand in June, and the global Phase 1/II dose-escalation study is dosing across three initial cohorts, with radiolabeled copper PET scans, ceruloplasmin and urinary copper as the biomarkers and follow-up scans at six to eight weeks. Proof-of-concept data are guided to 2027. 6 The alpha-1 antitrypsin deficiency program remains on track for a regulatory filing this quarter and for early clinical data in 2027, with serum alpha-1 levels readable within one to two weeks of treatment. 6 The ex vivo chronic granulomatous disease program, an autologous edited stem-cell therapy, has shown benefit in two patients, and Reine said the FDA has aligned on a filing supported by that two-patient dataset. 6
Reine described liver delivery as established across nuclease editing, base editing and, before long, prime editing. The brain is the opportunity he says is least solved. "If in 5–10 years, I hope to be treating many of those diseases with Prime Editing," he said. 6
Cellectis trades CAR-T for in vivo editing
Cellectis will stop developing lasme-cel and eti-cel, its allogeneic CAR-T candidates, and rebuild as an in vivo gene-editing company. 7 The board approved the change on September 11 and the company announced it on September 14, with trading in its Paris-listed shares halted for the day. 7 The stated reason is commercial rather than scientific: better frontline regimens in B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma have reduced the number of patients who reach later lines of treatment, while bispecific antibodies and in vivo CAR-T approaches have crowded the same space, slowing enrollment and lengthening the path to registration. 7
Two assets now carry the company. The first, .HEAL-101, is a TALE base editor targeting APOC3 delivered in lipid nanoparticles for severe hypertriglyceridemia, a population Cellectis estimates at one to two million patients in the United States and Europe. 7 In preclinical work the editor reached a mean of more than 70% on-site base editing in a hepatic cell line and about 55% in humanized mouse liver, cutting circulating APOC3 by 60% to 70% and triglycerides by about 45%, with a deeper reduction of up to 68% in a hypertriglyceridemic model. 7
The second, .HEAL-201, works through a different mechanism: a TALE epigenetic modulator aimed at the PCSK9 promoter, also in lipid nanoparticles, for severe hypercholesterolemia. 7 An epigenetic editor changes how much of a gene is made, while the underlying sequence stays as it was. In a hepatic cell line the construct drove a mean of more than 90% on-site epigenome editing, and in humanized mice it lowered plasma PCSK9 by a mean of more than 90%. 7
Both programs are headed for Phase 1 investigator-initiated trials in China, with preliminary data for .HEAL-101 guided to the second half of 2027 and for .HEAL-201 to the first half of 2028. 7 Cellectis says the realignment extends its cash runway into the second half of 2028 and retains its cell-therapy collaborations with AstraZeneca, Allogene, Servier and Iovance. 7
Serapha Bio fills out its bench
Serapha Bio appointed five senior officers on September 15, led by Kenneth T. Mills as chief executive. 8 Mills was the founding chief executive of REGENXBIO and remains its board chairman; Daphne Karydas joins as president and chief financial officer from Flare Therapeutics; Weston Miller becomes chief medical officer from Epicrispr Biotechnologies; Nina Hunter becomes chief development officer after six years at REGENXBIO and twelve at the FDA, where she rose to director of the Office of Clinical Policy and Programs; and Shiva Fritsch becomes chief corporate affairs officer. 8
The program the team inherits is SERP-01, a lipid nanoparticle carrying messenger RNA for a proprietary adenine base editor plus a guide RNA, designed to correct the SERPINA1 E342K mutation that causes the PiZZ form of alpha-1 antitrypsin deficiency. 8 The FDA has cleared an IND for a Phase 2/3 trial, which Serapha intends to start in late 2026 or early 2027, and has granted the program orphan drug and Regenerative Medicine Advanced Therapy designations. 8 The clinical evidence so far comes from an investigator-initiated trial run by sites in China and Germany, presented at the European Respiratory Society congress earlier in September: dose-dependent increases in alpha-1 antitrypsin above the protective threshold, falls in the toxic Z isoform, direct correction of the target mutation, and no bystander or off-target editing detected by the assays used. That trial is early, involves few patients and was not designed to support approval. 8 The Boundless Bio merger is expected to close in the fourth quarter, on roughly $230 million of pre-closing private investment co-led by RTW Investments and RA Capital Management.
Safety and governance
The Lancet turns to delivery
The Lancet published an editorial on September 12 titled "Gene-editing therapies: delivering safely for patients." 9 It opens on Victoria Gray's account of sickle-cell crises and her 2019 treatment with the therapy now known as Casgevy, then notes how far the field has spread since: editing T cells as a leukemia therapy, and editing liver cells for transthyretin amyloidosis and metabolic conditions. 9 The editorial's first requirement is that genome editing reach the patient through the safest delivery systems available, which puts the constraint on the vector and on manufacturing. 9
China's Decree 818 gets an accountability test
Nature Biotechnology published a comment on September 15 by Jianqiang Wu on Decree 818, the rule covering hospital-based cell, gene and individualized therapies in China. 10 The comment's argument is that the decree's value depends on two things the text cannot guarantee by itself: consistent application across institutions, and reporting when outcomes are adverse. 10 The argument lands on ground this channel covered in its September 11 issue, when Nature examined the deaths of two children in Chinese gene-therapy trials and the gaps in how those trials were authorized and monitored. 17 For sponsors weighing investigator-initiated work in China, the operational question is whether serious adverse events surface in the published record.
Research frontier
Nature published "Targeted genomic integration and rearrangement using prime assembly" this week from Daniel Bauer's group at Boston Children's Hospital. The method uses CRISPR-targeted dual flap synthesis, in which prime editing writes a flap on each DNA strand to tether an incoming fragment, letting the team assemble and integrate single- or double-stranded DNA at chosen sites. 18 The group applied it to exon recoding, transgene integration and megabase-scale rearrangements, including at therapeutically relevant loci in primary human cells, and reports activity in both dividing and non-dividing cells, a range homology-directed repair cannot reach. 19 "By using prime editing to write in one flap per strand of the genome, the method controls exactly where the DNA replacement starts and ends," Bauer said. 19 The method itself was reported in this channel's August 28 issue; what is new in this paper is the scale of the rearrangements and the demonstration in primary human cells. The group's next step is delivering the components to disease-relevant cells in vivo, starting with hematopoietic stem cells. 19
FDA regulatory watch
CBER's "What's New for Biologics" ledger carried the Fayuvi approval letter on September 17, a September 15 approval for a liquid formulation of topical bovine thrombin, two approvals of red-cell preservation solutions, a draft guidance on electronic submission templates for premarket approval applications, and the October 1 advisory committee notice. 11 The October 1 session of the Vaccines and Related Biological Products Advisory Committee covers strain selection for 2027 Southern Hemisphere influenza vaccines. 12 Between September 12 and 18 the agency posted zero product-specific gene-editing approvals, complete response letters or advisory committee notices. 11 Fayuvi now appears on the agency's list of licensed cellular and gene therapy products. 20
The June draft guidance on leveraging prior knowledge in genome-editing products remains the standing reference point for editing submissions, and its comment period closed September 1. 13
What to watch next
- October 30, 2026 — the deadline for sponsors to apply to the Expedited IND pilot, with the FDA's 8-to-10 selections expected after that. 3
- Fourth quarter of 2026 — the Boundless Bio and Serapha Bio merger close, followed by the SERP-01 Phase 2/3 start guided to late 2026 or early 2027. 8
- Year-end 2026 — CTX310 Phase 1b data in severe hypertriglyceridemia and CTX611 Phase 2 top-line data. 5
- This quarter and 2027 — Prime Medicine's alpha-1 antitrypsin deficiency filing, then proof-of-concept data from Wilson's disease. 6
- March 10, 2027 — the PDUFA target action date for Intellia's lonvo-z, set when the FDA accepted the application under priority review in September. 21
- Ongoing — whether Chinese institutions report adverse outcomes under Decree 818, which is the test the Nature Biotechnology comment sets. 10
References
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- 2Ultragenyx Announces Approval of FAYUVI Gene Therapy
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- 4Vertex Reports Second Quarter 2026 Financial Results
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- 11What's New for Biologics
fda.gov
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- 15Vertex Reports Third Quarter 2025 Financial Results
investors.vrtx.com
- 16Vertex Reports Fourth Quarter and Full Year 2025 Financial Results
investors.vrtx.com
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