A affected person in a medical trial for a Regenxbio gene remedy developed a mind tumor, main the FDA to clinically halt the research. This pause impacts one other Regenxbio gene remedy that’s anticipated to obtain a regulatory choice within the coming week.

The most cancers case was reported in a Part 1/2 trial of RGX-111, a possible therapy for the uncommon enzyme deficiency Hurler syndrome, Regenxbio introduced on January 28. The inherited illness leads to the buildup of compounds in tissue, resulting in organ dysfunction and central nervous system issues. Enzyme alternative remedy is a typical therapy, however engineered enzymes don’t cross the blood-brain barrier. RGX-111 delivers a gene to the cells of the central nervous system to direct manufacturing of the poor enzyme to the central nervous system.

Regenxbio makes use of adeno-associated viruses (AAV) to ship its gene therapies. One identified threat of AAV-based gene remedy is that the viral vector may introduce materials into or close to a gene that causes most cancers. Based on Regenxbio, the most cancers case was recognized throughout a routine mind scan of an asymptomatic five-year-old trial participant who obtained the gene remedy 4 years in the past. The corporate stated preliminary genetic evaluation of the excised tumor detected an AAV gene insertion integration related to overexpression of a gene that regulates cell progress.

Regenxbio stated the affected person stays asymptomatic. Investigations are underway to find out whether or not the most cancers is said to the gene remedy. No proof of most cancers was reported within the 9 different research individuals who obtained RGX-111, the corporate stated. But the FDA additionally positioned a medical maintain on RGX-121, Regenexbio’s experimental gene remedy for Hunter syndrome, one other uncommon enzyme deficiency. That is essential as a result of this gene remedy is at present below evaluation by the FDA with a goal date of February 8 for a regulatory choice.

RGX-121 was initially anticipated to obtain a regulatory choice final November, however the company’s request for longer-term information from all 13 sufferers within the pivotal research prolonged the goal date to February. Based on Regenxbio, the FDA’s rationalization for pausing each the Hurler and Hunter syndrome trials is the similarities within the merchandise, the research populations and the shared threat between the medical trials.

Regenxbio remains to be ready for the formal FDA letter for extra particulars. The corporate famous that no circumstances of most cancers had been reported within the 32 sufferers who obtained RGX-121 for Hunter syndrome. However it’s unlikely the FDA’s questions and considerations may be answered earlier than the February 8 deadline. Beneath the Prescription Drug Reimbursement Act, an extension can solely be granted as soon as per evaluation cycle. So if the FDA does not approve RGX-121, that might imply the remedy will get a full response letter.

“We’re shocked by the FDA’s choice to droop our RGX-121 program whereas investigations into this single, unclear incident in RGX-111 proceed,” Curran Simpson, president and CEO of Regenxbio, stated in a ready assertion. “These are separate therapies, and the constructive security profile of RGX-121 in additional than 30 sufferers handled, together with these dosed practically seven years in the past, stays unchanged.”

Here is a abstract of different latest regulatory developments:

Extra regulatory setbacks

– Valneva voluntarily withdraws the chikungunya vaccine Ixchiq from the US market. Final August, the FDA suspended the authorization of Ixchiq after reviews that some who obtained the vaccine developed a chikungya-like sickness. Valneva stated the FDA lately advised the corporate it is going to clinically pause extra testing of the vaccine after a newly reported critical adversarial occasion. There are at present no trials vaccinating sufferers with Ixchiq, however Valneva stated it is going to proceed with deliberate post-market medical actions, topic to session with related regulatory authorities.

—The FDA has denied Pierre Fabre Prescribed drugs’ utility fortafelecleucel, a cell remedy developed to deal with Epstein-Barr virus-positive post-transplant lymphoproliferative illness (EBV+PTLD) after failure of ordinary remedy. The rejection got here practically a 12 months after the company issued a full response letter figuring out a single GMP-related deficiency. The corporate stated there have been no considerations about security, efficacy or medical trial design. Based on Pierre Fabre, the brand new FDA letter stated the company now not considers the single-arm research adequate to assist accelerated approval and that the company now needs new medical trials.

Tabecleucel was initially developed by Atara Biotherapeutics, which obtained European Fee approval for the remedy in 2022. Pierre Fabre beforehand signed a deal to commercialize this remedy in Europe, the Center East, Africa and rising markets. Final 12 months, Atrara transferred the FDA licensing utility for biologics to Pierre Fabre.

—Outlook Therapeutics is one other firm that will have but to conduct a medical trial. The FDA has denied the biologic drug authorization utility for ONS-5010/Lytenava, developed to deal with the “moist” type of age-related macular degeneration. Based on Outlook, the FDA letter stated extra mechanistic and pure historical past information from the resubmission demonstrated efficacy, however the company continues to suggest extra confirmatory proof of efficacy. The corporate stated the FDA has not specified what kind of proof can be acceptable.

—Corcept Therapeutics obtained an entire response letter for relacorilant, a remedy developed to deal with sufferers with hypertension because of hypercortisolism. Based on the corporate, the company acknowledged that the pivotal research of the drug met its main endpoint. Nevertheless, Corcept stated the company couldn’t attain a positive risk-benefit evaluation for the remedy with out the corporate offering extra proof of efficacy.

—The FDA has rejected Vanda Prescribed drugs’ utility for tasimelteon, model identify Hetlioz, as a therapy for jet lag dysfunction. Based on Vanda, the FDA concluded that the medical trial information for the drug doesn’t present substantial proof of efficacy for jet lag circumstances, particularly as a result of the medical trial design of shifting bedtimes by 5 and eight hours isn’t analogous to precise air journey, which the company stated contains decreased oxygen stress, bodily limitations, noise and modifications in lighting. Vanda disagrees with the FDA’s conclusions.

A medical grip lifted

—Intellia Therapeutics has obtained approval from the FDA to renew Part 3 testing of the gene remedy nexiguran ziclumeran (nex-z) as a possible therapy for polyneuropathy related to the uncommon illness hereditary transthyretin amyloidosis (ATTR). Final October, the company clinically halted this research and performed a separate Part 3 trial for ATTR cardiomyopathy after a affected person within the cardiomyopathy research developed liver problems. That affected person later died. Intellia stated analysis into polyneuropathy will proceed with improved liver monitoring. The corporate has additionally elevated enrollment from 50 to 60. The Intellia firm remains to be working with the FDA on the medical ready interval for the cardiomyopathy research.

Drug Approvals

– Imaginative and prescient dysfunction startup Tenpoint Therapeutics obtained FDA approval for Yuvezzi, a once-daily eye drop for presbyopia. It’s the first accredited product for Tenpoint, which added the attention drop to its pipeline by a 2024 merger with Visus Therapeutics. Tenpoint has secured $235 million in financing to assist the business launch of Yuvezzi, anticipated within the second quarter of 2026.

– Blockbuster Johnson & Johnson drug Darzalex Faspro expanded its approval to newly recognized sufferers with a number of myeloma who will not be eligible for an autologous stem cell transplant. The regulatory choice covers the usage of the injectable drug together with the usual a number of myeloma routine of bortezomib, lenalidomide and dexamethasone. The most recent approval marks the twelfth indication for Darzalex Faspro and the fifth indication for newly recognized a number of myeloma.

—Nexplanon, an implantable contraceptive marketed by Organon, has expanded its FDA approval to permit its use for as much as 5 years, up from three years. Within the medical trial supporting this growth, no pregnancies had been reported and there have been no new security findings. However the product label replace is accompanied by a brand new Danger Analysis and Mitigation Technique (REMS), a program to watch and handle security dangers. Organon stated the REMS is meant to scale back problems that will come up because of improper insertion or removing of the implant. Organon stated this new security plan will likely be accessible from February 23.

—The European Fee has accredited the antisense oligonucleotide drug Dawnzera for routine prevention of recurrent swelling assaults in sufferers aged 12 years and older who’ve the uncommon illness hereditary angioedema. Ionis Prescribed drugs designed the remedy to focus on a protein known as prekallikrein. The FDA accredited Dawnzera final August; Otsuka Pharmaceutical owns the rights to the drug in Europe.

—The ultra-rare inherited neurodegenerative dysfunction Menkes illness has obtained its first FDA-approved remedy, a drug developed by Sentynl Therapeutics. In Menkes, a genetic defect hinders the power to soak up and transport copper, which is important for sure physique processes. Sufferers develop, amongst different issues, seizures and developmental delays; most kids with Menkes don’t dwell past the age of three. Zycubo is a copper alternative remedy given by injection twice every day.

— Vanda Prescribed drugs’ neurokinin-1 receptor blocking capsule tradipitant, model identify Nereus, obtained FDA approval for stopping exercise-induced vomiting. Vanda stated the drug is the primary new pharmacological therapy for movement illness in additional than 40 years. Nereus is designed to be taken as a single dose roughly 60 minutes earlier than an occasion anticipated to trigger vomiting because of train.

Different FDA Actions

—The FDA is asking makers of GLP-1 medication to take away details about suicide from their labels. The affected merchandise are Saxenda and Wegovy from Novo Nordisk and Zepbound from Eli Lilly. On the time of approval of those merchandise, this threat was said within the “Warnings and Precautions” part of every label. The FDA stated an in depth research discovered that there isn’t a elevated threat of suicidal ideas or habits related to GLP-1 medication.

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