LONDON, 29 June (APM) - Europe is on course to approve its first two CAR-T cancer therapies after positive recommendations on Friday for both Novartis’s Kymriah and Gilead’s Yescarta.

The European Medicines Agency (EMA)’s advisory committee CHMP said that Kymriah (tisagenlecleucel) should be available in the region for the treatment of acute lymphoblastic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL).

Yescarta (axicabtagene ciloleucel), which Gilead gained rights to on its acquisition of Kite Pharma, is recommended for the treatment of DLBCL and primary mediastinal B-cell lymphoma (PMBCL).

HTA discussions

The positive opinions mean it is likely that both advanced immunotherapies will be approved by the European Commission in a matter of weeks, kicking off what will likely be tough conversations on how the different healthcare systems will pay for these expensive one-off products.

Kymriah, which was the first CAR-T approved in the U.S. last year, has a U.S. list price of $475,000, while Yescarta, which was approved several months later, is priced at $373,000 there (APMMA 54839, APMMA 55345).

European health technology assessment (HTA) bodies such as England’s NICE, the Scottish Medicines Consortium (SMC) and Germany’s G-BA have already begun discussions about how to assess the value of these products, which pose a particular challenge as they are given as a one-off treatment at a high cost compared to most drugs, whose use is spread out over a period of time.

Potential solutions include performance-based payments over time (APMMA 57421), with NICE’s chief executive Sir Andrew Dillon telling APM last year that his organisation and the National Health Service (NHS) in England will need to think “more creatively” about payment structures (APMMA 55652).

PRIME scheme

Despite the remaining uncertainties over market access, the recommendation for the two CAR-T therapies is a pivotal moment for the EMA: the products are the first medicines supported through its PRIority MEdicines (PRIME) scheme to receive positive opinions from the CHMP.

This scheme provides early and enhanced scientific and regulatory support to medicines that have the potential to address patients’ unmet medical needs to a significant extent.

They were also both assessed as advanced therapy medicinal products (ATMPs), meaning they were reviewed by the EMA’s Committee for Advanced Therapies (CAT), an expert committee for cell , gene or tissue-based medicines.

Dr Martina Schüssler-Lenz, chair of the EMA’s CAT, said in a statement: “CAR-T cells transform the fight against serious and often fatal diseases in the EU. Kymriah and Yescarta offer an innovative approach where patients’ cells are reprogrammed and reinjected to attack the cancer.”

Safety concerns

The main safety concern related to the administration of CAR-T cells is cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and neurologic toxicities.

To help combat this, the CHMP is also recommending Roche’s RoActemra (tocilizumab) to treat this side effect.

The EMA is also mandating use of a patient registry to monitor the long-term safety and efficacy of these therapies, as a condition for the marketing authorisation.

Dr Tomas Salmonson, chair of the CHMP, said: “From the beginning, we have worked to establish a robust system of data collection for the post-authorisation phase that would suit the specificities of these two medicines. We have used a wide range of tools - scientific advice, a specific workshop on patient registries for CAR-T cells, PRIME, to name just a few, to enable us to define the methods to tightly monitor the benefit-risk profile of these medicines and manage their risks once they are on the market, so that patients can benefit from these innovative treatments.”

Watershed moment

Liz Barrett, chief executive of Novartis Oncology, said in an emailed statement: "The positive CHMP opinion for Kymriah is a watershed moment for pediatric and adult patients in Europe with aggressive blood cancers.

“This truly transformative therapy helps address a profound unmet need, and Novartis is proud that our leadership in CAR-T innovation will make a meaningful difference to patients in the EU."

The company added that additional regulatory filings are under review for Kymriah in Canada, Switzerland, Australia and Japan.

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