Issue 198
When Chekhov spoke of the long winter, he saw a seasonal journey bleak, dark and bereft of hope… But, in the world of medicine, there is always light at the end of the tunnel. In a major advance, the FDA has approved two gene therapies that target sickle cell disease. Though the approval for Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy was anticipated, the regulatory verdict on Bluebird Bio's Lyfgenia came as a surprise; the PDUFA date was originally set for December 20.
When two therapies receive simultaneous approval, there will likely always be one that emerges in the media as a favorite. Unfortunately for Bluebird Bio, it’s not Lyfgenia. Initially, both therapies will be restricted to patients aged 12 and above with the most severe form of the disease, and both will carry a high price tag. Casgevy undercuts Lyfgenia with a US list price of $2.2 million (versus $3.1 million) – and it doesn’t suffer the same black box warning for the risk of blood cancer.
The Vertex-CRIPSR therapy is also making headlines for being the first ever FDA approved therapeutic to use gene-editing technology. The approval marks a new era in medicine. “Casgevy’s approval by the FDA is momentous: it is the first CRISPR-based gene-editing therapy to be approved in the U.S. As importantly, Casgevy is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with sickle cell disease,” Reshma Kewalramani, CEO and President of Vertex, said in a statement.
Ultimately, these therapies are long-awaited potential cures for a debilitating and life-threatening disease that affects more than 100,000 in the US. Let's hope the patients who need it most will experience a transformative change in their lives as these therapies become available – a date set for early 2024.
What thoughts do you have on these recent approvals? Drop me a line at [email protected].
Until next week,
Jamie Irvine | Associate Editor
Essential Reading
ALL in tandem
ViroCell Biologics has entered a partnership with University College London to advance the development of their CAR T-cell therapy for relapsed pediatric acute lymphoblastic leukemia. Their approach involves preserving early "stem cell memory" T-cells and dual targeting with both CD19 and CD22 CAR T-cells to prevent antigen-negative relapse. ViroCell has been selected as the manufacturing partner and will provide lentiviral vectors for UCL’s phase I CARPALL cohort 4 clinical trial, expected to commence in Q2 2024.
FDA update
Just over a week since the FDA's disclosure of a safety evaluation concerning sanctioned CAR-T therapies, Poseida Therapeutics has presented data for a Roche-partnered candidate characterized by a nonviral modality that could offer an enhanced safety profile. The early findings come from an investigation into the allogeneic CAR-T therapeutic candidate developed by the San Diego-based biotechnology firm, denominated P-BCMA-ALLO1. Specifically targeting B-cell maturation antigen and marked by a T stem cell memory-abundant chimeric antigen receptor, this therapy is being assessed in a clinical trial for individuals grappling with relapsed or refractory multiple myeloma.
Worth Your Time...
Business
RoslinCT to manufacture first ever FDA approved CRISPR-based gene therapy Casgevy in US and UK.
Orchard Therapeutics receives Swissmedic approval for Libmeldy – hematopoietic stem cell gene therapy in early-onset metachromatic leukodystrophy.
Marker Therapeutics report sustained complete response in first lymphoma patient treated with mt-601 following anti-CD19 CAR-T cell therapy relapse.
Research
Researchers suggest AAV-PKP2 gene therapy holds promise for circumventing arrhythmogenic right ventricular cardiomyopathy associated with Plakophilin 2 mutations.
Study finds unexpected resistance to CAR-T therapy where tumor cells interacting with in vivo tumor microenvironment induce adaptive T-cell resistance program.
Scientists show promising antitumor activity with EpCAM–CAR-T cells co-stimulated by Dectin-1 in both pre- and clinical investigations for solid tumors.
