By Max Rex, Analyst
It’s been difficult to keep up with the flurry of reimbursement news coming out of England relating to the recently approved CAR-T therapies Kymriah (Novartis) and Yescarta (Gilead). Despite only having gained EMA (European Medicines Agency) approval in late August this year, England’s medicines watchdog, NICE (National Institute of Health and Care Excellence), has been hard at work evaluating these new and revolutionary cancer therapies. Here is a summary of the key events from the last two months:
- June 28th – Kymriah and Yescarta gets positive CHMP (Committee for Medicinal Products for Human Use) recommendation
- August 27th – Kymriah and Yescarta granted full European approval by the European Council (EC)
- August 28th – NICE rejects Yescarta for diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL)
- September 5th – NHS England recommends Kymriah for B cell acute lymphoblastic leukemia (ALL) for reimbursement through the Cancer Drugs Fund (CDF), after negotiating a commercial deal with Novartis
- September 19th – NICE rejects Kymriah for DLBCL
- October 5th – NHS England recommends Yescarta for DLBCL and PMBCL for reimbursement through the CDF, after negotiating a commercial deal with Gilead
The outcomes of these assessments have been mixed so far – both Kymriah and Yescarta were both initially not recommended by NICE for the treatment of DLBLC (a commercial deal changed this in the case of Yescarta). There were common themes across the two assessments, including uncertainty over the true clinical benefit of the drug. There were two key reasons for this:
- The use of single-arm studies with no comparator
- A lack of long-term follow up data to show the long-term effects
What’s the problem?
- Most European HTA bodies have issues when the only data submitted by a company is from single-arm studies. Their concerns all encompass the fact that they cannot be certain of the level of benefit that a treatment is giving patients over a placebo or the standard of care. However, many drugs have previously been given reimbursement across Europe in similar circumstances, showing that it is not a deal-breaker in any of the major markets
- Long-term follow up data is always difficult to show in clinical trials. Italy has a sophisticated network of patient registries that are often used to track patients who have been given a new drug. This longer-term data collection from the real world can be used by companies as a way of relieving payer fears about efficacy
Also flagged in both assessments was the high occurrence of adverse events caused by the therapies, which is hardly surprising. The safety issues of CAR-Ts have been widely reported, with cytokine release syndrome (CRS) being the cause of multiple deaths across the clinical trials so far. Companies must build the cost of treating these adverse events into their cost-effectiveness models, which can reduce the likelihood of being recommended by NICE. However, the adverse events did not play a huge role in why NICE came to its decisions in these cases.
Potential for future deals?
In the near future, it would not be a huge surprise if Novartis and NHS England negotiated a commercial deal for Kymriah in DLBCL patients, similar to Yescarta. Kymriah was already seen as more cost-effective than Yescarta in that indication, and Simon Stevens, chief executive of NHS England, has been clear from the outset that the NHS will be able to provide patients with CAR-T therapies, so long as manufacturers are not extortionate with their prices. Given Novartis just negotiated an access deal for Kymriah’s other indication, there is a decent chance that another deal will follow.
The European journey has only just begun…
Now we must wait and see the decisions of the EU’s other major HTA bodies. Each agency has its own idiosyncratic methodology for assessing medicines, so the decisions by NICE are by no means a definitive guide for how these CAR-T assessments will pan out across the EU. Manufacturers may be in for more of a battle in France, where there is no precedent of reimbursing gene therapies and there are growing concerns about the budget impact of new drugs. Price-volume agreements and revenue caps are commonly used methods of controlling their spending and may well need to be used to secure access for these CAR-T therapies. Germany, on the other hand, has previously approved multiple cell and gene therapy products, and the AMNOG system is appropriate for the approval of such innovative and expensive therapies.
Although the first HTA decisions have been quite promising for Novartis and Gilead, there are still many potential bumps in the road to securing access across Europe. There will be many lessons to be learned about how each country views this technology, and companies developing other CAR-Ts would be wise to take not.
#cell and gene therapy #rare diseases #NICE
For more information on CAR-Ts and the outlook for patient access in Europe, download our ‘CAR-T Therapies, the future for cancer patients? A market access perspective’ White Paper at https://partners4access.com/enlightened-opinion/publications-white-papers/