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Leiden University Medical Center (LUMC) will start this year with the construction of the largest non-profit stem cell and gene therapy facility in the Netherlands, and one of the largest facilities in Europe. In the ‘NECSTGEN’ facility, the Netherlands Centre for the Clinical advancement of Stem Cell and Gene Therapies, research will be conducted in the field of regenerative medicine; medicine that restores or replaces diseased cells, tissues and organs. In NECSTGEN, researchers are working on the breakthroughs of the future, such as insulin-producing cells grown on demand for diabetes patients.

Source: LUMC constructs the largest stem cell facility for the Netherlands and beyond | LUMC

ZURICH (Reuters) – Novartis won European approval for its gene therapy Zolgensma for the hereditary disease spinal muscular atrophy (SMA), the Swiss drugmaker said on Tuesday, adding it is in talks over price with countries in hopes of a quick launch.

Source: Novartis wins conditional EU approval for gene therapy Zolgensma – Reuters

The ESGCT has started a series of webinars on diverse topics related to gene and cell therapy that can be viewed on their YourTube channel every Wednesday 14:00 hrs CET. For more information click here.

The European Medicines Agency has recommended approval for Alnylam’s Givlaari (givosiran) for acute hepatic porphyria (AHP). This is the second RNA interference (RNAi) drug to secure approval in both the European Union and the United States, and the first treatment for AHP, a rare and life-threatening genetic condition in which patients lack the enzymes needed to produce heme.

Givlaari is an mRNA-targeting siRNA drug that lowers the expression of aminolevulinic acid synthase 1 (ALAS1), a liver enzyme that is involved in an early step in heme production. By downregulating ALAS1, the drug in turn lowers blood levels of aminolevulinic acid and porphobilinogen, neurotoxic intermediates that are associated with AHP symptoms including severe abdominal pain. In a six-month pivotal trial, patients treated with Givlaari experienced 70% fewer porphyria attacks than did placebo recipients. Common adverse reactions included nausea and injection site reactions.

The FDA approved the drug in November 2019. Analysts forecast annual global sales of $560 million for the siRNA candidate by 2025, according to data from the Cortellis database.

The only other approved RNAi drug is Alnylam’s transthyretin-directed patisiran, approved in 2018 for hereditary transthyretin-mediated amyloidosis.

Alnylam, the RNAi pioneer, is also testing the utility of its emerging modality in other late-stage development programs. Its lumasiran, directed at hydroxyacid oxidase 1 mRNA, is under review in both the United States and European Union for primary hyperoxaluria type 1. The company is also running phase 3 trials of a next-generation transthyretin-directed candidate, vutrisiran, for transthyretin-mediated amyloidosis.

Another RNAi drug under regulatory review is the cholesterol-lowering agent inclisiran. The PCSK9-directed siRNA drug was developed by Alnylam, licensed to The Medicines Company and then acquired last year by Novartis. And Sanofi, under license from Alnylam, is testing the thrombin-directed fitusiran in pivotal trails in hemophilia.

Source: Second RNAi drug approved | Nature Biotechnology

An adult with congenital blindness is the first person to receive an in vivo CRISPR-based therapy, according to the sponsors of the clinical trial: Editas Medicine and Allergan. The trial is testing whether EDIT-101 (also known as AGN-151587) can remove a point mutation in the CEP290 gene, which causes type 10 of the retinal degenerative disease Leber congenital amaurosis (LCA). The IVS26 mutation leads to a functional loss in the CEP290 protein, which causes defects in retinal photoreceptors and severe vision loss. To correct the IVS26 mutation, EDIT-101 uses a construct containing the adenovirus vector AAV5 with two guide RNAs to identify the location of the IVS26, combined with DNA encoding the Cas9 enzyme under a promoter specific to photoreceptor cells. Another gene therapy for LCA is Luxturna (voretigene neparvovec-rzyl) from Spark Therapeutics, now owned by Roche. Both Editas and Spark use an AAV vector, but whereas Editas’s genome editing corrects the mutation, Spark’s agent introduces a correct copy of the affected gene. Luxturna is approved for treating specifically the form caused by mutation of the retinal pigment epithelial 65 (RPE65) gene.

In the Editas trial, 18 adult and pediatric participants will receive subretinal injection in a single eye, with any vision improvements anticipated within four weeks of treatment. Also developing a therapeutic for LCA is ProQR Therapeutics. Early results from a phase 1/2 trial of sepofarsen (QR-110), an RNA-based antisense oligonucleotide therapy, showed about 60% of participants improving.

Although EDIT-101 is the first trial using a CRISPR agent inside the body, Sangamo’s zinc finger nuclease therapy SB-913 was the first gene therapy used in vivo, to treat patients with the inherited metabolic disorder mucopolysaccharidosis type II. Until now, clinical trials using CRISPR-based agents had been ex vivo: patients’ cells are removed, edited and then returned to the body. Initial results from a trial of CRISPR Therapeutics and Vertex’s CTX001 in patients with hemoglobin-related blood disorders suggested potentially curative responses in patients with β-thalassemia and sickle cell disease.

Source: First CRISPR therapy dosed | Nature Biotechnology