FDA staff raises concerns over lack of safety data for sickle-cell treatment

BLOOMBERG

The Food and Drug Administration’s (FDA) staff raised concerns about safety data on a potential gene-editing treatment for sickle cell disease, ahead of a closely watched meeting where scientific experts will weigh the first therapy using Crispr technology.
FDA advisers are preparing to meet on October 31 to consider and discuss an application from Vertex Pharmaceuticals Inc and Crispr Therapeutics AG to use a Crispr-based treatment for people with the painful blood disorder.
Crispr makes precisely targeted changes in DNA that researchers are trying to use to repair flaws in patients’ genomes related to inherited disease. It isn’t clear if the genetic diversity of patients studied by the companies in their safety analysis “is sufficient to adequately assess” the risk that the treatment would make unintended changes in patients’ DNA, the FDA staff said in a report, or that it can “adequately capture variants in this population across the United States.”
Shares of Vertex fell 1% in New York, while Crispr Therapeutics fell less than 1%.
The report also published data from a clinical trial by the companies that found 93.5% of subjects met the primary goal, which was freedom from pain crisis for 12 months after treatment.
Sickle cell is an inherited disease where patients have red blood cells that are inefficient and misshapen, leading to clogged blood vessels and painful crises when tissues fail to get enough oxygen. The two partners are seeking approval to edit the genes of people with sickle cell disease so that they make a different, oxygen-carrying form of hemoglobin.

Potential Relief
The treatment promises potential relief — and possibly a cure — for the condition that affects some 100,000 Americans. The life expectancy of people who have sickle cell disease and are covered by Medicaid and Medicare is about 53 years, according to a study published in July.
Crispr has been heralded as a way to eliminate genes linked to cancer, blood disorders and blindness. Yet regulators have viewed it caution, citing the risk that alterations that may go beyond the treatments’ intended targets. Some health advocates have also said the expected high cost of the one-time treatments threatens to leave out patients who can’t afford them.
In the experimental procedure, the companies remove blood stem cells, edit them in a lab using Crispr and then infuse them back into patients’ bodies.
The FDA advisory committee will meet to evaluate the data and hear company presentations. The FDA itself makes the final decision on whether to clear the therapy for sale.

‘Pretty Benign’
The briefing documents are “pretty benign,” according to analysts at RBC Capital Markets. While earlier efficacy data is more impressive than that in the briefing documents, they still reaffirm potential for approval, the analysts said in a note.
But for safety data, it’s hard to say which way the agency is currently leaning. “Regulators will be looking for reassurance from the panel of experts that necessary tests are in place to mitigate against the risk,” of unintended DNA changes, Jack Allen, a senior research analyst at Baird, said in a note.
No vote has been scheduled, according to the draft agenda. Instead the FDA has set aside almost two hours to discuss concerns and provide recommendations for the gene-editing technique, according to meeting documents. The narrow focus of the panel discussion and lack of a voting questions are positive signs, William Blair analysts said.
The Blair analysts believe the meeting “will be supportive of exa-cel’s therapeutic profile and will be a catalyst for the stock,” they said in a note.