Vertex Pharmaceuticals Seeks Alternatives to CRISPR Gene Editing Treatment For Sickle-Cell

Tuesday - December 19 2023, 05:00 UTC - 11 months ago

Vertex Pharmaceuticals has been approved to sell the world's first CRISPR gene-editing treatment for sickle-cell, but due to its immense costs, complexity, and unequal acceess, Vertex is actively seeking alternatives to this treatment. Vertex is aiming to come up with a pill to alleviate sickle-cell and perceptibly reduce the moral dilemma of unequal access. Three strategies suggested by David Altshuler, Head of Research at the company, are finding a substitute to chemotherapy, a drug that lets the edited cells latch on to the bone marrow, and a separate drug that alleviates the symptoms of sickle-cell without any gene editing.

The company that just got approval to sell the first gene-editing treatment in history, for sickle-cell disease, is already looking for an ordinary drug that could take its place. Vertex Pharmaceuticals has a 50-person team working "to make a pill that doesn’t do gene editing at all," says David Altshuler, head of research at the Boston drug company. "We’re trying to out-innovate ourselves," he says .

Vertex won approval in the US to sell the world’s first treatment using CRISPR, the gene-editing technique, on December 8. It took eight years to develop, and at huge expense. Regulatory documents filed with the government during the approval process exceeded a million pages. Yet now that medicine’s CRISPR era has begun, some of the technique’s limitations are already visible. The treatment, called Casgevy, is both tough on patients and hugely expensive .

Patients must spend several weeks in a hospital as doctors remove, genetically edit, and then reintroduce their bone-marrow stem cells, which make blood. The treatment will cost $2.2 million, not including hospital costs, according to Vertex. The company proved the gene fix can be a permanent remedy for people who have the most severe sickle-cell symptoms. These individuals, numbering around 16,000 in the U .

S., suffer recurring pain crises when misshapen red blood cells block blood vessels in their bodies. But it’s unclear how many Americans will opt for gene editing. In an opinion column for MIT Technology Review, one patient who got the treatment, Jimi Olaghere, said the bone-marrow replacement an "intense months-long journey" that will create barriers to access. "It’s simultaneously a miracle and has a drawback that prevents wide use," says Geoffrey von Maltzahn, a partner at Flagship Pioneering, who leads biotech ventures but was not involved in the sickle-cell treatment .

"That is a common duality." Such drawbacks are why a pill to alleviate sickle-cell, if developed, could sweep CRISPR from the playing field. A pill version could also resolve a brewing moral dilemma: Vertex so far has no plans to offer its gene-editing treatment in those countries where sickle-cell is most common. A wide ribbon of lower-income nations across the middle of Africa, including Nigeria and Ghana, account for 80% of sickle-cell cases but, according to US researchers, lack the hospitals, medical expertise, and money to implement this complex intervention .

"One question I get a lot is: How are we going to get to the rest of the world?" says Altshuler. "And I think the answer is not by trying to do bone-marrow transplants in the rest of the world. It’s just too resource intensive, and the infrastructure is not there. I think the goal will be achieved sooner by finding another modality, like a pill that can be distributed much more effectively." In an interview with MIT Technology Review, Altshuler outlined three ideas Vertex is exploring to improve on its breakthrough CRISPR treatment .

One is to come up with a substitute for the intense chemotherapy that’s used to kill a person’s bone marrow and make space for the edited cells to take over. Vertex and other ge­ne-editing companies are experimenting with molecules that specifically target immune cells that must be cleared before the edited cells can colonize the space. Another strategy: come up with a drug that makes it easier for the edited cells to latch onto the bone marrow and start producing blood cells .

Finally, Vertex has a massive program dedicated to finding an entirely separate drug that alleviates the symptoms of sickle-cell without any gene editing.