Pay-For-Performance Deals Help Solve ATMP Access Barriers In Europe
Executive Summary
New regulations on health technology assessments pose both a threat and an opportunity for getting advanced therapies to market in Europe, while pay-for-performance deals can solve the problem of high up-front payments, said speakers at an event organized by the Alliance for Regenerative Medicine.
New EU regulations on health technology assessments (HTAs) could be a double-edged sword, said speakers from industry at the Cell and Gene Meeting on the Med on April 20-22. While the new rules could solve some of the challenges in assessing advanced therapies, including a lack of data at launch, they could also lead to added burden for companies.
Speakers at the event organized by the Alliance for Regenerative Medicine (ARM), which represents companies developing advanced therapy medicinal products (ATMPs), also revealed that pay-for-performance deals had been key to securing market access. However, they warned that these agreements, which see payment tied to outcomes targets being met, were not always plain sailing.
Speakers voiced concern that the new HTA Regulation (Regulation (EU) 2021/2282) would lead to added burden for companies and become an extra hurdle to clear before products can reach the market. The regulation was intended to improve access to innovative new medicines, make better use of available resources and improve business predictability, according to the European Commission.
The most significant change that the regulation brings is making all medicines and some medical devices subject to an EU-level joint clinical assessment that will assess the clinical value of a product and which will inform national decision making on pricing and reimbursement. (Also see "The Implications Of The New EU HTA Regulation For Companies" - Pink Sheet, 30 Mar, 2022.) Initially the idea was that EU member states would be bound by the conclusions of the joint clinical assessment, however the language was softened and member states must only give the assessment due consideration. ATMPs will become subject to the joint clinical assessments from 2025.
Klaus Langhoff-Roos, corporate vice president at Novo Nordisk’s cell therapy commercial unit, believes that the new regulation offers an opportunity for companies. ATMPs face a challenging journey to reimbursement but the right methodology for the joint clinical assessments could change this, for example, if it accepts the limited nature of data at launch and the need for long-term follow up and if it recognizes the value of ATMPs. However, if the methodology fails to do this, then the regulation could become an additional burden, he warned.
Sissel Rodah, senior vice president of commercial operations at GenSight Biologics, warned that because member states are not bound by the outcome of the joint clinical assessments, companies could still be asked to make similar submissions on a national level. This would mean a bigger workload and further delay, she said. “I think it will remain to be seen whether it can provide faster access for patient.”
Robin Kenselaar, senior vice president and general manager, EMEA, Orchard Therapeutics, added that even after a joint clinical assessment, which considers only clinical value, the same barriers to reimbursement would remain.
Pay For Performance
One such challenge that has not been resolved is how payers can pay large lump sums for ATMPs that are used as one-time treatments and potentially offer life-time benefits. “It's perceived as a big chunk of money at one time, and this system just can't cope with that. We have been discussing it for years now,” said Dick Sundh, head of Australia, Canada and Europe, Kite Pharma.
Sundh added that in theory the industry could find ways for them to pay over a number of years, for example over 20 years if that is how long patients benefit from the drug. However, he is skeptical that a simple long-term payment agreement could work in practice. “But of course, all of us have been in this industry for a long time and we realized if we do that, they will find some reason that they don't need to pay after three years. We're not prepared to do it,” he said.
Nevertheless, speakers agreed that pay-for-performance agreements were offering solutions. These can help payers deal with the uncertainty that come with ATMPs, for example limited data at the time of launch and doubts about how long benefit will last. Such agreements have proved successful for Kite. “We would have never been able to commercialize the way we have done if we hadn't been really active with pay for performance,” Sundh said. Some 70% of Kite’s reimbursement deals have been outcomes based, he noted. Kite is a Gilead Sciences company that developed the CAR-T therapies Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel).
Kenselaar added that there is a greater willingness among payers to consider outcomes-based deals and that they had been instrumental in getting the company’s gene therapy Libmeldy (atidarsagene autotemcel) to patients.
Meanwhile, Rodahl agreed that there was willingness to look at innovative payment schemes but warned that many barriers remained. “Things like how do you follow up, how do you collect the data that is needed and even the GDPR [General Data Protection Regulation] regulations can be a barrier.”
According to Sundh, agreements were easier to implement for chimeric antigen receptor (CAR) T-cell therapies because the data point monitored for the agreements was overall survival – or whether the patient was alive or not at a certain point in time. “That makes it a lot easier for the system to track. And this is the biggest hurdle we have when implementing this going earlier in the lines of therapy.”
He said that Yescarta will soon be available for patients with earlier stage diffuse large B-cell lymphoma, which means that for these patients the product will not be an end-of-life treatment. This could mean it is more difficult to concretely show the effects of the drug and to convince payers to pay for it, he said. For example, if patients receive subsequent treatment it may be more difficult to quantify the efficacy of the drug and decide how much can be attributed to different treatments.
Meanwhile, Sundh warned that risk should be managed on both sides. “That means when I deliver on my promise you pay me in full, not a 20 to 30 or 40% cut. When I deliver it’s full payment it’s the list price. But in return when I don't deliver, I give you a significant discount or maybe under certain circumstances even for free.”
Rodahl advised that responsibility for setting up these agreements largely falls on companies. They need to approach and engage with payers very early on and establish partnerships, she said. Companies “must try to understand [payer] needs and put themselves in their shoes.”
Comparative Data
Another issue in commercializing ATMPs is the need to provide comparative data for these products which largely treat rare conditions.
As Kenselaar explained, if there are no comparators and no active therapy on the market, clinical trials can be more difficult. In such cases, regulators are more accommodating and accepting of a lack of comparator arm if the treatment under review is highly innovative and meets a clear unmet need. However, for products that treat conditions for which other therapies are available, regulators are more likely to demand that the product is compared against another treatment, said Sundh.
This becomes more difficult, particularly when comparators are innovative, more expensive products. “This is not like a small molecule that you can buy cheaply from a pharmacy and make a comparator arm. You are going to go and buy these from your competitors to do a clinical trial, which maybe they don't want you to do, it's going to be really challenging.”
Sundh believes the way forward is to use synthetic comparator arms, which would use real-world data taken from real-world source for comparison.
For Yescarta’s first indication the company created its own synthetic arm using historical data with which the product could be compared. “I don't think that we would be able to get pricing and reimbursement without that synthetic arm. So this was truly a success factor.”