Delving into the Latest Updates on Rebisufligene etisparvovec with Synapse

RegulationPriority Review (United States), Fast Track (United States), Orphan Drug (United States), Orphan Drug (European Union), PRIME (European Union), Regenerative Medicine Advanced Therapy (United States), Rare Pediatric Disease (United States)

Login to view timeline

Structure/Sequence

Sequence Code 1310778347

Source: *****

Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is a single gene (SGSH) childhood onset neurodegenerative disease for which gene therapy is in clinical trial. Theoretically, the transfer of a working gene should enable functional expression of the defective protein and rescue the phenotype when administered before the onset of irreversible disease. Recombinant adeno-associated virus (AAV) is being used as a vehicle for a number of gene therapy applications and the neurotropism of serotype 9 affords utility for monogenetic neurological disorders. To assess the efficacy of restoring the underlying biochemistry in the MPS IIIA brain, tail vein injections of self-complementary AAV9 human N-sulfoglucosamine sulfohydrolase (scAAV9.U1A.hSGSH) at 3 × 10¹³ vg/kg were administered to 6- and 16-week-old MPS IIIA mice. Heparan sulfate (HS) and G_M2 and G_M3 gangliosides were cleared from the cortex, hippocampus and subcortex with residual storage remaining in the brain stem and cerebellum. SGSH activity increased in the brain of the MPS IIIA-treated mice, but remained significantly reduced compared with wild-type. Motor activity as assessed in an open-field arena, and gait length, improved in MPS IIIA mice treated at both 6 and 16 weeks of age. However, functional assessment of cognition in the water cross-maze test, as well as gait width, normalized in mice treated at 6 weeks of age only, with mice treated at 16 weeks performing similar to untreated MPS IIIA mice. Astrogliosis was reduced in mice treated at 6 and 16 weeks of age compared to untreated MPS IIIA mice. These results demonstrate that the gene product is actively clearing primary HS and secondary ganglioside accumulation in MPS IIIA mice, but in older mice, neurocognitive impairments remain. This is likely due to secondary downstream consequences of HS affecting neurological functions that are not reversible upon substrate clearance.

82

News (Medical) associated with Rebisufligene etisparvovec

17 Sep 2026

·firstwordpharma.com

Ultragenyx gets FDA nod for Sanfilippo gene therapy

Ultragenyx Pharmaceutical secured its second gene-therapy approval in less than a month when the FDA cleared Fayuvi (rebisufligene etisparvovec-hopf; UX111) as the first treatment for paediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A. Company shares jumped more than 12% on the news Thursday."Achieving meaningful neurodevelopmental benefit through a single intravenous administration represents a significant scientific milestone — demonstrating that systemic AAV9-mediated gene delivery can reach the central nervous system at therapeutically relevant levels in paediatric patients," said Megha Kaushal, acting deputy director of the FDA's Office of Therapeutic Products.Ultragenyx said it received a priority review voucher following the approval. MPS IIIA is a rare inherited disease in which mutations in the SGSH gene lead to a deficiency of the sulfamidase enzyme that in turn causes heparan sulfate to build up in the body, including the brain. Children can lose cognitive, language and other developmental capabilities over time.Fayuvi is designed to address the underlying defect via a one-time intravenous infusion of an AAV9 vector carrying a functional copy of SGSH. The treatment enables cells to produce sulfamidase, allowing the accumulated heparan sulfate to be broken down in lysosomes.Prior CRLIt wasn't a straight line to approval, however. US regulators issued a complete response letter in July 2025 citing concerns about chemistry, manufacturing and controls (CMC) following facility inspections. Ultragenyx resubmitted the BLA in January with responses to the CMC observations and also included additional longer-term clinical data requested by the FDA.In February, however, Ultragenyx disclosed it had received an incomplete response letter regarding the resubmission and was asked to provide additional supportive documentation related to its CMC responses.Fayuvi was evaluated in an open-label, single-arm study that measured mean changes in cognitive scores in patients between the ages of 2 and 5 years old. On the cognitive function domain of the Bayley Scales of Infant and Toddler Development (Bayley-III), patients treated with Fayuvi achieved a mean 22.7-point improvement on cognitive raw score, versus a decline of 6.8 points typically seen in natural history data. Gene therapy recipients showed significant gains in receptive and expressive communication scores, as well as fine motor function. They also saw a median 66% reduction of heparan sulfate in cerebrospinal fluid.Fayuvi carries warnings about the risk of thrombotic microangiopathy, while commonly reported adverse reactions include elevated liver enzymes, nausea and vomiting, fever, reduced appetite and decreases in white blood cell and platelet counts. As with other AAV-based gene therapies, the label notes there is also a possible long-term risk that inserted genetic material may integrate into the genome and lead to tumour development.Price pending"Our focus now is on supporting timely access in the US as we work closely with treatment centres and payers to support families on the gene therapy treatment journey," said CEO Emil Kakkis. The company hasn't yet released pricing details for Fayuvi though a useful benchmark might be Genglycos (pariglasgene brecaparvovec-opnr), its first approved gene therapy. The FDA cleared the AAV8-based treatment, indicated for glycogen storage disease type Ia, last month (see – Spotlight On: Ultragenyx sets $2.7 million price for newly approved GSDIa gene therapy).Ultragenyx expects Fayuvi to be available within the next month or two.

Drug ApprovalGene TherapyPriority ReviewClinical Result

03 Sep 2026

·www.fiercebiotech.com

Ultragenyx fails phase 3 Angelman test, plots ‘significant expense reductions’

Ultragenyx had been flying high after its recent FDA approval for Genglycos—but the company has been brought back down to earth with a damaging phase 3 flop. The late-stage Aspire trial was assessing its investigational asset apazunersen in Angelman syndrome, a rare genetic condition that affects the nervous system and causes severe physical and learning disabilities. The trial was a bust. The drug missed its primary endpoint of change from baseline in Bayley-4 cognitive raw score, while also falling short in its secondary endpoint, which was net response on the Multidomain Responder Index, a measure of clinical function. The company did not give specific figures or a breakdown of the trial. The Ultragenyx executive team's statement on the failure was refreshingly honest, with no attempt to shine a positive light on the poor results. “Based on everything we observed in the robust Phase 1/2 clinical development program and long-term extension study, we are disappointed by the Aspire result,” said Emil Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx, in a release. “Even more, we are disappointed for the global patient community who has invested so much in early-stage research, working to bring a first-ever treatment to their children.” The flop sent Ultragenyx shares down 43% after hours Wednesday evening on the news. The future of the drug remains in the balance with Ultragenyx saying that it's now looking over the apazunersen program “in light of this outcome and [will] make a decision on its disposition.” This has also prompted the biopharma to “assess its planned operations to define and implement significant expense reductions.” No further details on what these reductions will look like were shared. At time of publication, Ultragenyx had not responded to Fierce’s request for more information. Ultragenyx has before warned of “expense reductions”, which eventually led to 10% of its workforce being cut back in February. This came after a pair of failed late-stage brittle bone disease trials. The new phase 3 setback comes just two weeks after the FDA gave an accelerated go-ahead to pariglasgene brecaparvovec-opnr, Ultragenyx’s AAV gene therapy for the rare genetic disorder glycogen storage disease type Ia (GSDIa), under the name Genglycos. The company is also poised for the potential approval of another gene therapy, UX111, in Sanfilipo syndrome, with a PDUFA date just weeks away on September 19. Analysts at William Blair were “disappointed” by the apazunersen data but said they had always viewed the trial as “high risk, high reward.” The shop said it sees this failure as a negative read through for the separate Aurora study, which is assessing apazunersen in patients with Angelman syndrome across genotypes and age groups. “We believe that even if the Aurora study meets its primary endpoint, commercialization will be challenging given the limited size of the addressable population,” they added. There are currently no cures or approved disease-modifying treatments for Angelman. There are other companies working on the condition however, with Ionis one of the furthest along, having this summer completed enrolment in its phase 3 Reveal trial for RNA-targeted antisense asset obudanersen.

03 Sep 2026

·www.biopharmadive.com

Ultragenyx to weigh ‘significant’ cost cuts as Angelman drug fails key study

Dive Brief:Ultragenyx lost almost half its value Thursday after reporting the failure of a key experimental treatment for the rare condition known as Angelman syndrome.Known as GTX-102 or apazunersen, the therapy missed on both the primary and secondary endpoints in the study, Ultragenyx said Wednesday after the market closed. There were no differences between the treated and control groups that could support efficacy, it said.Ultragenyx now plans to evaluate the GTX-102 program and make a decision on its disposition. In the meantime, the company is looking for significant expense reductions as it focuses more on approved products and strives toward profitability in 2027.Dive Insight:Investors had eagerly anticipated the Phase 3 study in Angelman syndrome after the treatment showed promise in early research. While study failure announcements can include a glimmer of hope about a certain subgroup or future analysis, the language from Ultragenyx leaves very little room for an optimistic interpretation, Leerink Partners analyst Joseph Schwartz wrote in a note to clients.The setback may also have a ripple effect. Two companies Ionis Pharmaceuticals and Oak Hill Bio are developing Angelman therapies that work in a similar way. Ionis shares fell 4% in early trading Wednesday; Oak Hill cut a deal in July to go public by the end of the year. Still, multiple analysts believe those companies may see better results by offering higher doses or superior potency.Angelman is a rare neurogenetic disorder that causes issues in both the brain and body. Some patients cant walk, and most cant speak; they need care their whole lives. The condition has no approved treatment and a history of unsuccessful attempts by drugmakers hoping to bring the first therapy to market.For Ultragenyx, the study outcome fundamentally shifts the view of the company for investors, Schwartz wrote. Although Ultragenyx has five approved products including its first gene therapy as of August it has yet to achieve profitability. None of its marketed medications are poised for blockbuster status. And the companys latest plan to seek cost cuts comes after layoffs and a restructuring announced in February.While Ultragenyx has another therapy for a rare condition called Sanfilippo syndrome that may be approved in coming weeks, the potential doesnt match whats now lost with the Angelman treatment, analysts wrote. Some expect peak sales for that medication, UX111, to reach $120 million to around $240 million, compared with previous estimates of $1.8 billion or more for GTX-102.The investment case has changed shape, Schwartz wrote to clients. Ultragenyx is clearly now a commercial and expense story rather than a pipeline execution story. '

Phase 3Gene Therapy

100 Deals associated with Rebisufligene etisparvovec

Login to view more data

R&D Status

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Mucopolysaccharidosis III	United States	Ultragenyx Pharmaceutical, Inc.	17 Sep 2026

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04360265 (LTFU-ABO-102, Company_Website) Manual	Phase 3	Mucopolysaccharidosis III	28	Rebisufligene etisparvovec	srzwogooog(blrtoojlhy) = ykfolibeqh wzfvmdbzry (ldqzjgqzkn ) View more	Positive	03 Feb 2026
				Rebisufligene etisparvovec (Age under 2 years old or in the early stages of the disease during treatment)	srzwogooog(blrtoojlhy) = eobupzimgk wzfvmdbzry (ldqzjgqzkn ) View more
GlobeNewswire Manual	Not Applicable	Mucopolysaccharidosis III	27	UX111 (ABO-102) AAV gene therapy	ruqgpzxgpd(jbjcoplwbh) = wvdhnrsaqp sbolvqhgep (pxiqphcydy ) View more	Positive	05 Feb 2025
				UX111 (ABO-102) AAV gene therapy (natural history data (ages 24-60 months))	ruqgpzxgpd(jbjcoplwbh) = tammosezmf sbolvqhgep (pxiqphcydy )
NCT02716246 (Transpher A, GlobeNewswire) Manual	Phase 2/3	Mucopolysaccharidosis III	17	UX111	afgbrqczsd(kldxqqymbj) = The individual EYC in cognitive raw scores showed a positive rate of change indicating either stability or gains from baseline in 16 of the 17 patients during the expected window of plateau into decline, defined as >30 months of age. ahbhgdbcha (ztsfneqjbb ) View more	Positive	06 Feb 2024
NCT04088734 (CTgov)	Phase 1/2	Mucopolysaccharidosis III	5	scAAV9.U1a.hSGSH	njadqoqbmb = hhxxrysgud uxszuvaavs (dxlzyljvlb, zxivbnsqrh - kpqrtsnqvg) View more	-	25 Jul 2023
NCT03315182 \| NCT02716246 (Transpher A, Corporate Publications) Manual	Phase 1/2	Mucopolysaccharidosis III	-	Rebisufligene etisparvovec	lefmoemodu(agmihivjfi) = qrmcaivkgd rlvbtnfrfg (rwqalckaao )	Positive	12 Feb 2021
NCT02716246 (Transpher A, ASGCT2020)	Phase 1/2	Mucopolysaccharidosis III CSF heparin sulfate (HS)	14	ABO-102 1 X 10^13 vg/kg	abmkvpfbbr(sxolsvmdnx) = Mild transient cellular immune responses have been detected in 8 out of 14 patients as assessed by ELISpot (interferon-gamma) lemuattocy (rmfwrkhuml ) View more	Positive	28 Apr 2020
				ABO-102 3 X 10^13 vg/kg
ESGCT2019	Not Applicable	-	-	Cohort 1 (5x1012 vg/kg)	sintmehtqw(iulmyavgvv) = 8 out of 14 patients showed mild transient cellular immune responses (ELISpot) mfjpihpbcd (vcvqjblluo ) View more	-	22 Oct 2019
				Cohort 2 (1x1013 vg/kg)