NHS advised not to cover hemophilia B treatment Hemgenix

NICE committee's guidance cites gene therapy's cost, long-term effectiveness

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.K.’s National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending that England’s National Health Service (NHS) should not cover the gene therapy Hemgenix (etranacogene dezaparvovec) for adults with hemophilia B.

The recommendation is based on uncertainty surrounding the long-term efficacy of the gene therapy, as well as concerns about whether covering its cost would be an acceptable use of NHS resources.

The draft guidance was open for public comment in July, and the evaluation committee will meet again in September to review public comments before issuing a final recommendation. Of note, these recommendations do not apply to people who had already started the hemophilia B gene therapy before the guidance was published.

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“People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop,” the document says.

Hemophilia B is caused by mutations in the gene that carries instructions for making the clotting protein factor IX (FIX). Currently, standard treatment involves replacement therapies that work by administering a functional version of the FIX protein, either as prophylaxis (preventive) therapy or as on-demand treatment for bleeding episodes.

Hemgenix is a one-time gene therapy that works to deliver a functional version of this gene to the body’s cells. It’s sold by CSL Behring. The therapy was granted conditional marketing authorization in the U.K. earlier this year, shortly after it was approved in the EU.

Approval of the therapy was based on data from the Phase 3 HOPE-B clinical trial (NCT03569891), in which 54 men with hemophilia B were given a one-time treatment with Hemgenix.

Results showed that, compared with the six months prior to entering the study when patients were on standard prophylaxis with replacement therapies, the adjusted annualized bleeding rate decreased by 64% from months seven to 24 after the gene therapy treatment. Rates of spontaneous and joint bleeds also fell, and the use of replacement therapies decreased.

Uncertainty about long-term effectiveness

In its draft guidance, the NICE committee said this evidence suggests that Hemgenix can reduce bleeding in the short term, but highlighted uncertainty about how effective it will be in the long run, as long-term data was only available for a handful of treated patients.

“The committee concluded that the long-term durability of [Hemgenix] was a considerable uncertainty,” the draft guidance states, adding that this uncertainty will be addressed only when more long-term data on the therapy become available in the future.

CSL has conducted analyses of data from HOPE-B and other studies to indirectly compare Hemgenix against replacement therapy prophylaxis. Results from this analysis suggested the gene therapy is better at preventing bleeding episodes, But, according to the NICE committee, this indirect comparison has a lot of notable issues.

“There are problems with this evidence, such as differences between studies in the methods used, and the definition and measurement of bleeding outcomes,” the draft guidance states. “So, the indirect comparison results are highly uncertain.”

In addition to questions about effectiveness, the cost of Hemgenix also was raised as an issue. In the U.K., the list price for the gene therapy is £2,600,000 (about $3.3 million). CSL entered into a commercial arrangement for the therapy that would have applied if the NICE committee had recommended the therapy for reimbursement.

Given the amount of uncertainty regarding its effectiveness, the committee said that Hemgenix might be cost-effective at a cost of £20,000 to £30,000 ($25,498 to $38,247) per each quality adjusted life year gained (QALY), a measurement used in economic analyses to estimate how much a medication will improve lives).

However, economic models showed the cost of the gene therapy was more than £100,000 ($127,490) per QALY gained. Models comparing Hemgenix against replacement therapy prophylaxis suggested the gene therapy was not the most cost-effective strategy.

Cost-effectiveness estimates ‘highly uncertain’

“The cost-effectiveness estimates are highly uncertain … and are above the range that NICE usually considers an acceptable use of NHS resources,” the draft guidance states.

Taking all these data collectively, the committee decided that Hemgenix should not be recommended for coverage by the NHS.