Cell and gene therapies, collectively termed Advanced Therapy Medicinal Products (ATMPs) in the EU, are top of mind within the biopharmaceutical industry. Pricing and reimbursement challenges, as well as healthcare systems’ ability and willingness to pay are well documented and frequently discussed. However, access is also hampered by the ability of the healthcare system’s infrastructure to deliver such treatments. Indeed, with the European Commission planning to investigate why so many centrally approved therapies are not reaching patients in their national countries1, we need to look at what innovative manufacturers can do to help the very systems they depend on.
Given the technical complexity of these new therapies, we see the potential for manufacturers to evolve from purely being a researcher and manufacturer to also becoming a service provider and full-time player in the public healthcare system. This evolution extends past the nascent idea of “value beyond the pill.” It means becoming more involved and integrated from (1) the point of diagnosis, through (2) manufacturing and delivery, to (3) patient access support.
1. Supporting Screening and Diagnosis Efforts
To date, many ATMPs have targeted niche indications for small and manageable patient populations that are often tight-knit and well informed about advances in research. These patients often follow the clinical development process and request the treatment at the time of launch. At the same time, however, patients and manufacturers face challenges through lack of awareness outside these communities, delayed diagnosis, and, where available, delayed treatment initiation.
Manufacturers are therefore pushing for additional efforts to optimize diagnosis and newborn screening. As an example, early diagnosis and fast treatment initiation is key in spinal muscular atrophy (SMA), as it is in most degenerative diseases. In Italy, where widespread SMA newborn screening is in its early stages, SMA therapy manufacturer Biogen is working with patient organizations to introduce a countrywide SMA newborn screening program2 with the goal of improving early diagnosis, facilitating early treatment onset, and improving treatment outcomes.
Although the goal of the initiative is to identify patients in need of treatment, it also provides a service to the wider public health system, ensuring patients receive the treatment they need.
While ATMPs currently focus on rare diseases and niche oncology indications, they are likely to move into mainstream indications as the understanding of technologies and disease progresses. Currently, there are:
- 1,066 clinical trials being conducted by manufacturers and researchers in the ATMP space (year-end 2019).
- More than 10 products awaiting approval with an estimated doubling in the next two years.3
2. Supporting Capacity Building in Hospitals and Staff Training
The increased complexity of ATMPs brings with it increased complexity in product handling. For many mainstream pharmaceuticals, the cool chain is the key element in the supply chain of the final product. ATMPs, however, may require “on-point” manufacturing, such as manipulation of individual patients’ stem cells. This requires collaboration and cooperation across several players, including laboratories, providers, and patients, while at the same time complying with government requirements.
“On-point” manufacturing also presents many other challenges. Patients often have to travel great distances for treatment. Financial concerns, language barriers, and logistical hurdles all add to the challenges of treatment delivery. In a scenario where the therapy “travels” to the patient, the manufacturer is dependent on air travel, which can be severely restricted by natural disasters or pandemics. Supply chain challenges ultimately have a direct impact on patient access to new therapies.
One recent example of government requirements is Germany’s request that hospitals meet certain criteria prior to administering a new CAR-T therapy, Gilead’s Yescarta. The Federal Joint Committee (G-BA) required hospitals to attain numerous qualifications before administering the therapy, including staff certification, training requirements, and emergency treatment center provisions.4
Only a few hospitals were initially able to meet the G-BA’s criteria, limiting patient access to Yescarta. This is despite the already recognized need for manufacturers to develop capacity within hospitals, exemplified by granting funds for dedicated nursing staff and developing specialty services for patients with rare diseases and cancers.5 In these instances, manufacturers were actively involved in the training, resourcing, and capacity planning for hospitals—tasks historically managed by governments.
3. Accessing Therapy—The Patient Journey
Once hospital training and certification is established, patients need to reach the treatment center. Some countries may have patient populations that are too small to support in-country treatment centers. In addition, access to the new therapy may be limited due to potential infrastructure or economic constraints.
Even before gene therapies became available, a trend was seen for new therapies to be offered only in select centers within a country. In such cases, physicians refer patients to another center that may be farther away, requiring the patient to relocate during treatment. With innovative therapies like ATMPs potentially not available in a patient’s home country, it means patients and physicians need to request treatment abroad.
In the EU, the pathway to access treatment abroad is regulated in the Social Security Regulation and Cross-Border Healthcare Directive. Strimvelis is a therapy dependent on this pathway. Developed by GlaxoSmithKline (GSK) in 2016, Strimvelis is a gene therapy for ADA-SCID that is available only in one center, in Milan, Italy. In its first year on the market, only one patient received commercial treatment. GSK argued that the delay was due to the challenges faced in organizing cross-border access for its European patients.6
The European Social Security Regulation ((EC) No 883/2004 and No 987/2009) lays the foundation for patients to seek treatment in another EU Member State. Requirements include, among others:
- There is no adequate alternative treatment available in the patient’s home country.
- The therapy needs to be reimbursed in the public system of the country of treatment.
- The patient seeks prior authorization from their home country.
- The regulation allows patients to seek care abroad without being liable to up-front treatment costs.7
In practice, a number of other challenges are also common, with barriers ranging from lack of information to governmental issues and willingness to pay.8 These roadblocks keep patients from accessing often lifesaving or life-improving therapies.
To help navigate the journey, manufacturers are stepping up to support clinicians, including working through regulatory and legal systems, as well as financial support for patient travel and cost of treatment. Again, these types of initiatives were previously organized by the healthcare system. Manufacturers, now more than ever, have the opportunity to take a more active role in developing a patient pathway to novel therapies, as they negotiate local reimbursement and access to their treatment for all patients.
Adapt, Adopt, Align for Better Public Health
While most analysis and discussions on cell and gene therapies have focused on access barriers based on willingness to pay, infrastructure, or more specifically the lack thereof, plays an equally important role. Manufacturers are adapting to the new challenges and adopting a broader role within the healthcare system. This does not only apply in EU markets, but similar developments are also relevant in the U.S. and other geographies, meaning it is important to understand the various opportunities within the appropriate legal frameworks.
While these expanded activities do serve to create access to a manufacturers’ own therapies, ultimately, they align with the greater societal need for improved public health and service to the wider community. It therefore remains essential that initiatives, though helpful and mutually beneficial, do not deviate from a healthcare system for all patients into a system for a select few. If done responsibly, we can anticipate more such initiatives moving forward as innovative new therapies continue to vie for limited resources within the healthcare system.
1. Health and Food Safety Directorate-General; European Commission. “Health Systems, Medical Products and Innovation. Medicines: Policy, Authorisation and Monitoring.” PHARM 797. 86th Meeting of the Pharmaceutical Committee; March 12, 2020; Brussels, Belgium. https://ec.europa.eu/health/sites/health/files/files/committee/ev_20200312_ag_en.pdf.
2. PRECISIONadvisors proprietary research.
3. Alliance for Regenerative Medicine. “The Alliance for Regenerative Medicine Releases 2019 Annual Report and Sector Year in Review [press release].” Published March 5, 2020. Accessed June 5, 2020. https://alliancerm.org/press-release/the-alliance-for-regenerative-medicine-releases-2019-annual-report-and-sector-year-in-review.
4. Gemeinsamer Bundesausschuss (Federal Joint Committee). “Axicabtagen-ciloleucel: Field of Application.” Accessed June 5, 2020. https://www.g-ba.de/downloads/91-1385-408/2019-05-02_Geltende-Fassung_Axicabtagen-Ciloleucel_D-406_D-416.pdf.
5. Novartis. Joint working. Accessed June 5, 2020. https://www.novartis.co.uk/partnerships/nhs/joint-working.
6. Mullin E. “A Year After Approval, Gene-therapy Cure Gets its First Customer.” MIT Technology Review. Published May 3, 2017. Accessed June 5, 2020. https://www.technologyreview.com/2017/05/03/152027/a-year-after-approval-gene-therapy-cure-gets-its-first-customer/.
7. “Regulation (EC) No 987/2009 of the European Parliament and of the Council of 16 September 2009 Laying Down the Procedure for Implementing Regulation (EC) No 883/2004 on the Coordination of Social Security Systems.” Accessed June 5, 2020. https://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1478533221777&uri=CELEX:32009R0987.
8. Kowalska-Bobko I et al. Health Policy. 2016;120(11):1233-1239.