RARE Daily

Vertex and CRISPR Amend Sickle Cell Disease and Beta Thalassemia Collaboration

April 20, 2021

Rare Daily Staff

Vertex Pharmaceuticals and CRISPR Therapeutics said that the companies have amended their collaboration agreement to develop, manufacture, and commercialize CTX001, an experimental CRISPR/Cas9-based gene editing therapy in development as a potentially curative therapy for sickle cell disease and transfusion-dependent beta-thalassemia.

Sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) are both genetic hemoglobinopathies that affect the ability of the blood to deliver oxygen to the cells throughout the body. In SCD, mutated hemoglobin causes the red blood cells to develop a sickle shape that impedes their flow through the body and causes anemia. TDT reduces the production of hemoglobin, the iron-containing protein in red blood that carries oxygen to cells.

Under the terms of the amended agreement, Vertex will lead global development, manufacturing, and commercialization of CTX001 with support from CRISPR Therapeutics. Vertex will be responsible for 60 percent of program costs and will receive 60 percent of profits from future sales of CTX001 worldwide, representing a 10 percent increase in program economics compared to the previous agreement. CRISPR will be responsible for 40 percent of costs and will receive 40 percent of profits. Additionally, CRISPR will receive a $900 million upfront payment, with potential for a $200 million payment upon the first regulatory approval of CTX001.

“As we take the lead on CTX001, we want to acknowledge the foundational contributions by the team at CRISPR Therapeutics,” said Jeffrey Leiden, executive chairman of Vertex. “Our increased investment in our partnership with CRISPR is based on the compelling clinical profile of CTX001, which shows its potential to be a durable cure for patients with SCD and TDT, and the rapid progress that we and our partners at CRISPR have made toward registration and commercialization. We see a significant commercial opportunity for CTX001, and we believe we will be able to further enhance that opportunity by fully leveraging the breadth of Vertex’s capabilities – including our established and proven R&D and commercialization expertise in serious diseases – to bring CTX001 to more patients around the world, more quickly.”

CTX001 is the first potential treatment to emerge under a 2015 co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. The partners believe it is the furthest advanced among gene-editing approaches being studied for TDT and SCD.

CTX001 is an experimental ex vivo CRISPR gene-edited therapy in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth and is then replaced by the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and painful and debilitating sickle crises for SCD patients. CTX001 is the most advanced gene-editing approach in development for beta thalassemia and SCD.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission for both TDT and SCD, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for SCD.

“Working with Vertex, we have made tremendous progress with CTX001, the first CRISPR/Cas9-based therapy to demonstrate proof of concept in the clinic and together we have broken new ground in the treatment of genetic diseases. We have now dosed more than 30 patients with CTX001, with longest follow-up beyond two years, and we are on track to complete enrollment in both clinical trials this year,” said Samarth Kulkarni, CEO of CRISPR Therapeutics. “Given the transformative results and momentum that we have generated with this program, we are adopting a new operating model to enable a globally coordinated launch of CTX001, leveraging Vertex’s best-in-class global capabilities and leadership in development, manufacturing, and commercialization to enable this medicine to reach all patients that can benefit from it as quickly as possible.”

Photo: Jeffrey Leiden, executive chairman of Vertex

Stay Connected

Sign up for updates straight to your inbox.