One after another, the men and women testified how a new gene-editing treatment had relieved their suffering from sickle-cell disease. They addressed a Tuesday hearing in which the Food and Drug Administration heard patients and scientists weigh in on what’s likely to be the country’s first-approved genetic treatment for the disorder.
Sickle cell has afflicted people of African descent for generations, causing agony and death among those who inherit its deformed red blood cells. At the daylong meeting, the FDA empaneled outside experts to review the gene-editing treatment, before the agency makes an approval decision.
Developed by
Vertex Pharmaceuticals
(ticker: VRTX) and
Crispr Therapeutics
(CRSP), the “exa-cel” therapy would also be the first product marketed in the U.S. that employs the Nobel Prize-winning technology called Crispr. The gene-editing technique is capable of targeting a troublesome stretch of a cell’s DNA and disrupting its mischief. The companies licensed the patents of the Nobel winners Emmanuelle Charpentier and Jennifer Doudna.
All but one of the dozens of patients treated with exa-cel in clinical trials have gone for more than a year without the blood-clogging crises of sickle cell, and have been spared the frequent hospital stays that those crises provoked. The one exception was a patient whose condition was aggravated by an infection, and his symptoms were relatively mild.
The drug firms seek FDA approval to market exa-cel for people over age 12 who have suffered repeated sickle cell crises. There are an estimated 20,000 Americans with such severe disease, among the 100,000 in total sickle cell sufferers. On average, someone with severe sickle cell dies in their mid-40s.
Nashville, TN, hematologist Haydar Frangoul told of his patients who now live normal lives, thanks to exa-cel. Before the gene-editing therapy appeared, Frangoul could only cure sickle cell with a bone-marrow transplant. A matching donor is only available for 15% to 20% of patients, he said, and those lucky patients must still take immune-suppression drugs for the rest of their lives.
FDA documents posted online in preparation for the meeting don’t reveal great concerns at the agency over exa-cel. After reading them last week, William Blair analyst Sami Corwin wrote that they set up “a near-best-case scenario” for the meeting—and for exa-cel’s approval as a treatment for sickle cell.
Corwin had wondered if the agency might have any doubts about the Crispr therapy’s safety and effectiveness. It seems not.
“Given the strongly positive results,” says the agency’s review document, “FDA does not believe that the study design limitations call the efficacy of exa-cel into question.” The FDA didn’t even schedule a vote by the advisory panel on whether the treatment’s been proven effective.
At the meeting, agency reviewers were mainly concerned with the exa-cel developers’ tests for off-target DNA edits that might cause side effects.
The day’s first expert witness was Fyodor Urnov, a University of California, Berkeley professor and gene editing pioneer (who has consulted for Vertex). Urnov said that laboratory techniques for predicting and detecting off-target edits have sharply improved in the last decade. But those bench tests are approaching their limits, he said, so further knowledge will come from actually treating patients.
“The technology is ready for prime time,” said Urnov.
Dan Bauer, the director of gene therapy at Boston Children’s Hospital, told the FDA gathering that off-target effects could be monitored with relative ease in a blood disorder like sickle cell.
There are drugs on the market that offer relief to many of the 100,000 Americans estimated to suffer from sickle cell. But patients are understandably eager for treatments that could be a one-time fix for their genetic disorder. They will welcome an approval of exa-cel, and for any of the crowd of other genetic treatments for sickle cell in line behind the Vertex/Crispr candidate.
That crowded field is one reason why shares of Vertex and
Crispr Therapeutics
haven’t gotten much lift from exa-cel’s approaching approval. Vertex has roughly tracked the
Nasdaq Composite
Index, while Crispr has lagged behind them both.
Other reasons for the stock market’s wariness are the exa-cel treatment’s complexity—which restrict it to transplant centers—and its expected high price tag—which could exceed $1 million and become a hard sell for the Medicaid programs that cover many sickle cell patients.
RBC analyst Luca Issi therefore wrote last week that the uptake of an approved exa-cel therapy could be slow. He expects exa-cel will take a long time to meaningfully lift the revenue of Crispr Therapeutics and Vertex—or their shares.
The gene-editing treatment will be the first of many, however. Improvements already under study at Crispr and elsewhere could yield cheaper, less complex fixes for genetic ills like sickle cell.
Write to Bill Alpert at [email protected]
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