ICER updates cost-effectiveness threshold for bluebird, Vertex and CRISPR's dueling sickle cell gene therapies

The potentially curative promise of gene therapies often carries a steep price tag. But for a pair of personalized medicine prospects in sickle cell disease (SCD), the cost could be worth it, at least as far as ICER is concerned.

Running its customary cost-benefit calculus, cost watchdog the Institute for Clinical and Economic Review (ICER) has unveiled a revised evidence report weighing the clinical effectiveness and value of two SCD gene therapy contenders: Vertex Pharmaceuticals and CRISPR Therapeutics’ exagamglogene autotemcel, also known as exa-cel, and bluebird bio’s lovotibeglogene autotemcel, which goes by the abbreviated name lovo-cel.

Overall, the two gene therapies—both racing neck-and-neck through the FDA for potential approvals in the back half of the year—would meet cost-effectiveness thresholds if priced between $1.35 million and $2.05 million, ICER said late this week.

Neither bluebird nor Vertex and CRISPR have announced potential U.S. prices if their drugs are approved.

Next up, ICER is set submit its evidence report for review at a public meeting of the watchdog’s independent appraisal committee, which will hear further testimony from stakeholders to deliberate on the meds’ comparative clinical effectiveness, other potential benefits and long-term value for money.

Peeling back the layers on ICER’s review, the organization determined that bluebird’s lovo-cel provides at least “incremental” net benefit versus standard of care in SCD, and that the gene therapy prospect may provide a “substantial net health benefit.”

As for Vertex and CRISPR’s exa-cel, the gene therapy candidate “may be comparable” to bluebird’s and could yield an “incremental net benefit, or result in substantial net benefit when evaluated against standard of care.”

ICER was quick to caveat that the gene therapies’ long-term safety and efficacy have “important uncertainties,” especially in the case of exa-cel, which is the first CRISPR therapy to apply for FDA approval.

“[T]he need for autologous bone marrow transplantation with these therapies means they come with important potential risks,” ICER’s chief medical officer, David Rind, M.D., said in a statement, adding that “the first CRISPR therapy necessarily has even greater uncertainties about longer-term risks and durability of benefit than a lentiviral gene therapy.”

Bluebird’s application for its sickle cell gene therapy lovo-cel landed at the FDA’s desk in late April, slightly behind a first-quarter 2023 goal. Under priority review, the drug is up for an FDA decision within about six months.

The filing came on the heels of a partial hold back in 2021, when the FDA held testing on the medicine after one case of persistent, nontransfusion-dependent anemia in an adolescent patient following treatment with lovo-cel.

Bluebird’s filing is just a few weeks behind Vertex and CRISPR's, which entered the regulatory review process on April 3.

In a note to clients earlier this year, analysts with William Blair wrote that Vertex and CRISPR’s potential head start won’t be as long as originally expected because of the close timing of the filings. They added that the FDA could hold a joint advisory committee meeting on the two applications.

If lovo-cel passes muster with regulators, it will become bluebird’s third approved gene therapy behind beta thalassemia treatment Zynteglo and cerebral adrenoleukodystrophy drug Skysona. Bluebird has set the U.S. prices for its gene therapies at $2.8 million and $3 million, respectively.