Gene-based therapies: opportunity vs access

The advent of CAR-T and CRISPR technologies are set to revolutionize cancer and genetic disease therapies, respectively. But with great hope comes great costs.

 

“The Centers for Disease Control and Prevention estimates that approximately 100,000 people in the US have sickle cell disease, making it the most prevalent inherited blood disorder. Remarkably, the new gene therapies offer very promising early efficacy: exa-cel and lovo-cel demonstrated 93.5% and 88% efficacy, respectively, in reducing vaso-occlusive crises (VOCs)—episodes leading to severe pain and organ damage—in the first 12 months after administration, in patients with recent prior severe VOCs. It remains unknown how gene therapies will affect other long-term sequelae of sickle cell disease such as pulmonary hypertension; cardiovascular and cerebrovascular events; and bone health.

 

“While offering the possibility of tremendous benefit, these treatments also present new challenges for patients, payers, and regulators. The necessary administration of high-dose chemotherapy may contribute to infertility and increased risk of secondary malignancies. Additionally, the long-term safety of gene editing is unknown, particularly the risk of off-target base editing. Furthermore, the extremely high cost of these therapies poses a substantial barrier to their widespread adoption both within the US and globally; for example, in the US, list prices for a single dose are $2.2 million for exa-cel and $3.1 million for lovo-cel.

“The rationale for such high prices for gene therapy is that they offer a large amount of value in a single dose, which should therefore be rewarded with a high price. In the case of sickle cell disease gene therapies specifically, prices have an added layer of nuance and precedent setting, raising the question: how should equity considerations be incorporated into drug pricing?”

Sickle cell disease primarily affects patients with genetic ancestry from Africa, the Middle East, Southern Europe, and the Indian Subcontinent. In the US, most patients with sickle cell disease are Black, an historically disadvantaged demographic. High prices are unaffordable for most countries, including those with the highest prevalence of sickle cell disease. How can we insure access to this transformative technology? 

“One category of such solutions would be to decouple financial rewards from costs to patients, such as federally funded grant programs specifically targeted at the development of therapeutics for historically underinvested diseases. This system would offer an opportunity to compensate sponsors specifically for developing treatments for underinvested diseases or to account for historical inequities and could target either early-stage development or act as a subscription-type or prize model to fund recently developed products. Importantly, such programs could offer incentives without increasing the willingness to pay threshold in cost-effectiveness evaluations for equity considerations or increasing the amount that patients and insurers have to pay for therapies targeting neglected diseases. Support for manufacturers could include funding to run clinical trials or incentives for trial completion (regardless of trial outcome) in historically underresearched conditions or conditions specifically targeting underserved populations, which might help to de-risk investments. Receipt of these incentives could be conditional on setting the drug’s US market price under a ceiling relative to the costs of production (e.g., no greater than 10%-20% more than the total costs of production).”

https://jamanetwork.com/journals/jama/fullarticle/2821828?guestAccessKey=02f47f07-02e4-45ef-a718-15fb393ddc57&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=080524&adv=000002935472