With the product being the process in the cell and gene therapy (CGT) space, I was excited to attend the 2023 Advanced Therapies Conference in London Excel. Outlined below are the two sessions that I found most impactful and interesting with regards to market access and pricing and reimbursement (P&R).
UK: There is positivity in the market access air
As CGTs have a healthcare system-wide impact, it was insightful to attend a UK focused panel discussion between senior representatives from the regulatory body MHRA, the HTA body NICE, NHS England (NHSE), and the branded industry association ABPI. This was focused on challenges and opportunities facing companies and other organizations in launching CGTs in the UK.
The MHRA spokesperson was keen to speak about the Innovative Licensing and Access Pathway (ILAP), subject to review as well as pilot studies since inception in January 2021. As a response to the UK leaving the EU, the ILAP was launched to reduce the time for manufacturers to market innovative drugs by harnessing the expertise from the MHRA and NICE. The MHRA revealed that the pilot Patient and Public Reference Group is integral to the ILAP Steering Group that decides about accepting an application on the pathway. The representative believes the ILAP is probably best for start-ups struggling in terms of regulatory expectations.
According to the NICE representative, ILAP allowed NICE to strengthen its relationship with the MHRA, such as on working on evaluation tools related to surrogate endpoints, commonly used in CGT trials. She also highlighted that at the end of 2022, NICE had recommended 11 out of the 12 CGTs evaluated. In fact, a month prior to the conference, the first baby received Libmeldy for metachromatic leukodystrophy on the NHSE.
Managed Access Agreements (MAAs) used for CAR-Ts via the Cancer Drugs Fund (CDF) were the NHSE delegate’s other success story. Interestingly, in January 2023, CAR-T Yescarta was the first CAR-T recommended by NICE for routine commissioning. It was recommended for certain types of lymphoma after collecting RWE through the CDF and follow-up clinical trial data under a MAA. There was also praise for the creation of the Innovative Medicines Fund (IMF) although no drug has gone through this pathway yet.
…but challenges remain despite reform at NICE
The ABPI representative praised progress with severity modifiers under the new NICE Manual for health technology evaluation. The severity definition has been broadened to beyond conditions eminently life threatening. However, he was keen to highlight that reimbursement outcome is still dependent on whether or not a CGT is evaluated under the single technology assessment (STA) or the Highly Specialized Technology (HST) program. Despite HST revisions, the ABPI previously complained that the selection criteria prevented some drugs treating very rare diseases from entering this likely to be more favorable route.
During the Q&A, there were also criticisms that NICE was still not empowered to address the cost-effectiveness assessment challenge related to discounting, applied in assessing drug costs and benefits occurring in different time periods. CGTs are very sensitive to discounting as the potential benefit accumulates over decades whilst costs are incurred in the present. NICE continues to apply the standard rate of 3.5% instead of 1.5%, despite the case for change consultation agreeing on the need for a lower rate. As such, the perceived cost-effectiveness is reduced because discounting does not apply to the CGT cost but does to the chronic comparator cost, if existent, and the benefit (in terms of lifetime quality-adjusted life year gains) is greatly reduced.
EUCOPE shines spotlight on RWE and the EU joint HTA
I was very keen to attend the packed-out session presented by trade association EUCOPE, a regular presenter on CGTs, that focused on the role of RWE among other EU-wide launch considerations.
According to the EUCOPE head, RWE can potentially bridge the evidence gap when clinical trial results are not compelling enough for payers to reimburse the high upfront cost of CGTs in ultra rare diseases due to the small sample size and lack of direct comparisons.
EUCOPE emphasized Germany’s G-BA as an active player due to the mandated registry for gene therapy Zolgensma for spinal muscular atrophy. This was viewed as a top-down approach seeking to identify data gaps (such as the direct comparison to Spinraza and Roche’s drug Evrysdi). If the manufacturer does not fulfil the gaps, legislation dictates that the drug’s reimbursement price must drop.
However, the trade association spokesperson also listed these challenges for RWE:
- Different requirements between regulators, HTA bodies, and payers
- Long-term adherence to data collection; and
- Fragmented EU data collection system
The EUCOPE representative called for alignment on RWE reuse and sharing since CGTs will be the first modality to undergo the joint EU HTA system in 2025. According to the representative, for comparator selection, in the worst case, payers could adopt a cost-containment lens, selecting the cheapest or even an off-label comparator, not part of clinical practice.
Although the EU HTA will not be legally binding within its member states, the EUCOPE spokesperson thought member states will probably follow the recommendations due to time and resource commitments. The spokesperson also believed that the joint clinical assessment report will represent a summary of a CGT’s global value dossier released a month after EU approval.
Implications and outlook
The England Rare Diseases Action Plan’s upcoming review on the effectiveness of all schemes (from ILAP, IMF to MAA) that are designed to facilitate early access to novel high-cost drugs for rare diseases will be important to monitor for those wishing to explore the market access potential for CGTs in England. Despite the cost-effectiveness threshold challenges, NICE continues to recommend gene therapies such as Libmeldy. In contrast, this MLD gene therapy has just witnessed a reimbursement rejection in Spain, whereby the budget impact analysis does not appear to consider the long-term societal cost-offsets related to the curative nature of CGTs.
Europe-wide, there is need for industry to continue advocating to the EC for further investment to improve high-quality RWE collection to support HTA decision-making as well as innovative outcomes-based agreements. Harmonization of evidence requirements across regulators and HTA agencies is also critical to facilitate greater acceptance of RWE as well as indirect treatment comparisons and surrogate endpoints. This could potentially occur with the establishment of robust joint EU HTAs in 2025.
