In a landmark announcement for the CRISPR field and the sickle cell disease (SCD) community, the U.K. authorities have granted approval to Casgevy, the CRISPR-Cas9 therapy formerly known as exa-cel developed by Vertex Pharmaceuticals and CRISPR Therapeutics.
The U.S. Food and Drug Administration (FDA) is expected to follow suit in the next three weeks, having issued a decision date of December 8. A further decision on Bluebird bio’s related SCD therapy should come later that month. The U.K. approval was announced by the Medicines and Healthcare products Regulatory agency.
CRISPR pioneers, scientists, and commentators took to the X social media platform to voice their delight at the news.
In a trio of tweets, Nobel laureate Jennifer Doudna, PhD (Innovative Genomics Institute) declared that she was “excited and a bit overwhelmed with emotion” on hearing the news. “Going from the lab to an approved [CRISPR] therapy in just 11 years is a truly remarkable achievement.” She added that she was “especially pleased” that this milestone helps patients with SCD, “a disease that has long been neglected by the medical establishment. This is a win for medicine and for health equity… Today is an extraordinary moment for the field, for patients in need, and for the future.”
Emmanuelle Charpentier, PhD, Nobel laureate and co-founder of CRISPR Therapeutics, told GEN:
“I am very excited and pleased as I reflect on what the first-approved CRISPR therapy means for patients and their families. This milestone certainly underscores the importance of fundamental research in the field of microbiology. I am truly amazed at the speed at which CRISPR research and applications have developed to get us to this historic moment. My most sincere acknowledgment goes to the team at CRISPR Therapeutics for their efforts and commitment to develop the CRISPR-Cas9 technology. This refers, in particular, to Rodger Novak, MD, former CEO of CRISPR, and Bill Lundberg, MD, former CSO. Without their leadership and vision at the time, we would not celebrate the first approval of a CRISPR drug these days.”
The CEO of CRISPR Therapeutics, Sam Kulkarni, PhD, called this a “momentous day” and said he was “proud of the team and the investigators and patients who were part of the trials. And excited for patients.” Co-founded by Charpentier, CRISPR Therapeutics initiated the SCD CRISPR therapy, eventually agreeing to partner with Vertex, which has since assumed the role of the lead sponsor.
Patrick Hsu, PhD (Arc Institute), one of the early developers of CRISPR genome editing working with Feng Zhang, PhD, called it “a huge victory for biotechnology, patients, and humanity.”
The Editor-in-Chief of The CRISPR Journal, Rodolphe Barrangou, PhD, (North Carolina State University), said the news was “very momentous for the field, ushering a new era of medicines and highlighting the momentum with regulatory agencies in a global context. A milestone for all.”
It was “remarkable to see that our discoveries over 15 years ago would enable such tremendous advances for [SCD] and thalassemia!!!” said Vijay Sankaran, MD, (Harvard Medical School), who led one of the pivotal genome wide association studies in 2008, published in Science, that pinpointed BCL11A as a critical regulator of fetal hemoglobin (HbF) levels. The last sentence of that report stated: “As a stage-specific component involved in the silencing of γ-globin expression, BCL11A, therefore, emerges as a new therapeutic target for reactivation of HbF in [SCD] and thalassemia.”
Physician-scientist Jay Bradner, MD, who recently stepped down as president of the Novartis Institutes for Biomedical Research, said the “first approval of a CRISPR therapeutic is a milestone for the technology innovators, but also for the biologists who directed the machinery.” He offered congratulations to Sankaran and his former boss, Stuart Orkin, MD, at Boston Children’s Hospital.
“It’s a historic day for mankind, scientific advancement, and patients waiting for gene-correcting treatments!” posted Nicole Gaudelli, PhD, head of the DNA editing platform at Beam Therapeutics. “For the first time, a Cas9-based medicine is approved. I am thrilled for the scientific community and the patients we serve. Onward!”
David Liu, PhD (Broad Institute), Gaudelli’s former PhD supervisor who has pioneered the development of both base and prime editing, called the news of the first CRISPR drug “a major milestone for science, for medicine, and for patients.” He offered congratulations “to the many scientists, doctors, patients and industry leaders who made this development possible.”
Janice Chen, PhD, co-founder of Mammoth Biosciences, offered her congratulations to the two biotech companies, the “entire CRISPR field and the brave patients for this historic moment! A new era of medicine has begun.”
For once, Fyodor Urnov, PhD, (Innovative Genomics Institute) who coined the term “genome editing” in 2005 when he was with Sangamo and is currently leading the charge alongside Doudna to accelerate the development of CRISPR therapies for a large number of addressable genetic disorders, was left speechless. His post read simply:
(That’s one exclamation mark for each year since the Nobel Prize-winning CRISPR paper. Urnov was more loquacious in this recent exclusive video interview with GEN Edge.)
Casgevy works by interfering with the transcriptional regulator, BCL11A, that acts like a wheel clamp to block expression of HbF after birth. The restored γ-globin beautifully compensates for the β-globin polypeptide that carries the SCD point mutation.
The first SCD patient to be dosed in the Casgevy trial, Victoria Gray, was treated by physician Haydar Frangoul, MD, and his team at the Sarah Cannon Institute in Nashville, TN, in July 2019. Like almost all of the dozens of other SCD patients in the trial, she is now healthy and free of pain crises or the need for blood transfusions or hospitalizations.
Gray recently spoke at an FDA Advisory Committee meeting to assess the safety of the Vertex therapy, particularly in regard to the faint possibility of “off-target” effects, in advance of the final U.S. approval decision.
While today’s approval is cause for celebration, reality may soon set in when Vertex announces the price of the “one-and-done” therapy, widely expected to be around $2 million. Hematologist Akshay Sharma, MD (St. Jude) warned: “Now the real work begins to make this therapy truly accessible to patients who need it the most.”
British lawyer and ethicist Julian Hitchcock, who has followed the CRISPR field closely, also raised concerns over pricing and accessibility to U.K. patients on the National Health Service (NHS): “But will we get it on the NHS? I’m dubious.”