Sanofi’s gene-editing alliance with Sangamo Therapeutics has yielded an experimental sickle cell disease treatment that recently posted encouraging early clinical data, but the pharmaceutical giant has decided to walk away from that therapy and terminate the entire agreement as part of a revamp of its overall genomic medicines strategy.
Rights to the partnered sickle cell therapy, SAR445136, will be returned to Sangamo by the time the alliance ends in the middle of this year. Brisbane, California-based Sangamo said Thursday that it plans to explore its options for the program, including finding a new partner.
Sanofi inherited the Sangamo alliance from its 2018 acquisition of Bioverativ. The initial deal paid Sangamo $20 million up front, with as much as $276.3 million more tied to milestones. The partnership focused on using Sangamo’s zinc finger nuclease gene-editing technology to develop new therapies for inherited hemoglobin disorders.
The sickle cell program was the most advanced one under the partnership. Sickle cell disease is an inherited disorder that leads hemoglobin, the oxygen-carrying blood protein, to take on a crescent shape. Treatments include blood transfusions. Sangamo’s SAR445136 is made by editing a patient’s stem cells so that they produce fetal hemoglobin, potentially providing a patient with functional hemoglobin.
Sanofi’s termination notice to Sangamo comes just weeks after encouraging early data were presented at the annual meeting of the American Society of Hematology. In four patients who received the therapy so far, none required blood transfusions and total hemoglobin had stabilized by week 26 following treatment. Also, fetal hemoglobin levels increased in all four patients. No adverse events were reported that were related to the experimental therapy.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
However, the field of genomic medicines for sickle cell disease is growing more competitive. Partners Vertex Pharmaceuticals and CRISPR Therapeutics are also taking a gene-editing approach to the disease. Last year, Vertex paid $900 million to get a bigger share of the responsibility and the potential economic windfall of the partnered therapy. Graphite Bio also uses CRISPR technology for its gene-editing approach to sickle cell disease; a clinical trial began late last year. Beam Therapeutics is gearing up to test its base-editing approach to the disease after recently receiving the FDA’s green light to start a clinical trial. A Bluebird Bio sickle cell clinical trial resumed last year following a temporary hold during an inquiry into whether the biotech’s gene therapy caused cancer. But last month, a partial hold was placed on the study for patients under 18 while the company investigates a case of anemia in a patient treated with the gene therapy.
The approaches taken by Vertex, Graphite, Beam, and Bluebird are all autologous—cells are removed from a patient, edited in a lab, and then reinfused back into the patient. Though Sangamo employs a different editing technology, the partnered therapy is also autologous. Sanofi might have seen the field of autologous sickle cell therapies as too crowded for its liking, leading to the decision to end the alliance with Sangamo despite the encouraging data so far.
In a regulatory filing, Sangamo said the pharma giant’s Dec. 30 notice “indicated that its termination related to Sanofi’s changes in strategic direction to focus on allogeneic universal genomic medicine approaches rather than autologous personalized cell therapies.” Allogeneic therapies are those that can be produced and made readily available, off the shelf. John Reed, Sanofi’s global head of research and development, said in Thursday’s announcement that the pharma giant will explore other potential collaborations as it transitions the autologous sickle cell program back to Sangamo.
The termination will become effective June 28, according to the filing. Between now and then, Sanofi will transfer data, information, and regulatory materials to Sangamo. The biotech said the Phase 1/2 sickle cell study should be completed as planned and the final patients will be dosed in the third quarter of this year. Until the agreement formally ends in June, Sangamo said it expects Sanofi will continue to pay the costs of that study. Sanofi is exiting the alliance before it becomes responsible for any major payments to Sangamo. The biotech said in the filing that Sanofi had paid it $13.5 million in milestone payments to date.
Sangamo’s pipeline includes other genomic medicines, some of them partnered. A gene therapy for hemophilia A has reached late-stage development under an alliance with Pfizer, though that study is currently under a clinical hold. Programs addressing a range of conditions are in preclinical development with partners that include Novartis, Takeda Pharmaceutical, Biogen, and Gilead Sciences.
Image: Meletios Verras, Getty Images
