Cell therapies hold tremendous promise for treating many diseases, but their commercial scalability has been called into question for some time. Now, as the world responds to an unprecedented global pandemic, we spoke to a few institutions that are either already CAR-T accredited or had recently begun to explore the accreditation process to gauge the impact of COVID-19 on CAR-Ts. The changes triggered by the pandemic may have long-term implications, not only for today’s CAR-Ts, but also for the next generation of cell therapies.
Here are four ways COVID-19 has affected the cell therapy landscape in the short term:
- Reduction in CAR-T utilization at some centers: Many CAR-T centers are taking a more critical view about who needs treatment now vs. who can wait until later. This approach is driven both by patient safety and financial considerations and largely affects adult DLBCL patients, especially those with worse status and or higher risk of adverse events. For the pediatric indications, institutions describe almost no impact. All in all, however, institutions that were already committed to CAR-T administration remain committed despite COVID-19. As a chief oncologist at a CAR-T center of excellence in a high impact COVID geography noted, “Our clinical team has taken a more critical eye as to who really needs CAR-T given financial pressures, but one thing that remains a commitment to us is that CAR-T will be part of our future.”
- Temporary pauses on clinical trials: Because of COVID-19, some hospitals report a setback in handling monitoring responsibilities required for clinical trials. Others, however, report no impact and are leveraging remote options.
- Renewed focus on telemedicine and outpatient monitoring for hospitals that had started this process before COVID-19: Hospitals that, pre-COVID, had already started moving some elements of CAR-T administration to outpatient or telemedicine have doubled down in this effort, while those that had not started this journey will face delays in getting started. Some institutions, facing reimbursement challenges for inpatient aspects of treatment and monitoring, had already been finding ways to shift the site of care, as appropriate for patient safety. For example, Vanderbilt designed a program that offers out-of-hospital, but close-proximity tele-monitoring for CAR-T post-treatment monitoring in a hospital room via hospital provided and configured technology such as iPads and Zoom. Other institutions are shifting to outpatient or telemedicine models for antibody infusions, screenings and consultations as well as monitoring.
However, hospitals that had not started the move toward outpatient or telemedicine for CAR-T patients said this would be one of their last of priorities as a result of COVID-19. They are likely to face notable delays in getting started. As the director of the CAR-T program at an academic center noted, “We wanted to start our outpatient CAR-T program in February 2020. Then COVID hit, so we put this on the backburner, indefinitely. Our appetite for risk is very low.”
- Delays for institutions that are not yet accredited: Hospitals that were considering starting the accreditation process, or were in the middle of the process, have shifted their priorities elsewhere. This will delay the ability of manufacturers to expand and scale their site of care model in the short term, until hospital priorities are re-set.
Today, CAR-T centers of excellence are managing through the pandemic with tremendous resolve, and don’t believe COVID-19 will have a significant impact on their future use and commitment to CAR-T. However, we believe the short term impact will have long-term implications that next generation cell therapy manufacturers must be prepared for. While some of these changes might have happened eventually, COVID-19 has accelerated timelines as treatment centers are being forced to adapt more quickly.
Here are the expected long-term implications of COVID-19 on the cell therapy landscape:
- COVID-19 may accelerate telemedicine and alternative sites of care opportunities, but it will not be the force that completes the transition to a localized, outpatient model. COVID-19 has accelerated health system acceptance and adoption of telemedicine (50% system increase in the month of March alone) and will likely do so at select institutions for cell therapy. Over time, we also may see home diagnostic and digital monitoring use, and alternative sites of care leveraged for select parts of the treatment journey.
However, COVID-19 on its own will not complete the transition to a fully outpatient CAR-T model. Outpatient enablement is the future of next generation cellular therapies, but many treatment centers require significant upskilling to accomplish this, including remote monitoring capabilities, outpatient sites of care and personnel trained on CAR-T and evidence-based protocols and guidelines. This will require well-coordinated, concerted investment and partnership between manufacturers and sites of care to scale.
- Treatment centers may continue being more critical about what cellular therapies they offer and with which manufacturers they partner. It’s not guaranteed that every treatment center will offer every CAR-T or cell therapy option. Considering the diversity of indications, most will not go so far as to just offer one, but will instead prioritize within indications with multiple options. Of the next 20 or so launches anticipated through 2025, multiple will be in DLBCL, non-Hodgkin lymphoma, and multiple myeloma, enabling this transition toward selective treatment center access and partnership. Winning in high-demand treatment centers will require a differentiated product and service model to become a CAR-T partner of choice.
- Evolving payer mix and increased general population reliance on Medicaid will make the complex CAR-T hospital reimbursement landscape even more difficult to navigate. With unemployment skyrocketing to nearly 20% after just two months of COVID-19 stay-at-home orders, ZS estimates that Medicaid enrollment could approach 5%, or about 16 million members, by the time the global pandemic subsides. Despite some recent steps toward more stable (yet inadequate) inpatient Medicare reimbursement with CMS’s 2021 proposed rule, hospitals will now have to contend with the state-by-state variability and general underpayment associated with Medicaid at higher frequency.
What does this mean for first-generation and next-gen CAR-T manufacturers? COVID-19 increases the importance of simplifying the model to enable more sites to onboard, and to ensure that certified sites can offer multiple cellular therapy options. For today’s commercial CAR-Ts, simplification and ease of use will be critical to avoiding swift replacement by newer, more agile technologies. For next-gen CAR-Ts, simplification is important, but on top of the upskilling required to accommodate newer technologies such as allogeneic CAR-Ts and BiTEs. Clinical differentiation remains table stakes, and next-generation manufacturers should develop a more holistic value proposition that emphasizes simplicity, long-term benefit and partnership.
First, minimize the financial challenges associated with CAR-T use through continued focus on alleviating reimbursement gaps. Advocate for system-level change (such as CMS policy shaping in light of the recent proposed rule to reimburse inpatient CAR-T within a new DRG at a rate of $240,000) while providing local-level support to enable successful negotiations. Ensure that treatment centers know what CAR-Ts mean financially, and partner on site-level solutioning.
Second, make it easier for sites toparticipate as CAR-T centers of excellence without having to make all-encompassing resource and financial investments given the post-COVID financial rebound that many hospitals will prioritize short term. This is not to suggest that patient safety and necessary certification requirements should be short-changed in any way. Simplification must occur within the constraints of what is required from a patient safety perspective.
- Operationalize and outsource: While some elements of a truly personalized cellular therapy process cannot be operationalized, other elements can be. As an example, centralized vs. local cryopreservation and outsourcing apheresis or diagnostic/ biomarker testing would impact resourcing and logistical investment at treatment centers. Solutions are yet to be defined, but the need to simplify to scale dictates that this receives further attention.
- Rethink the manufacturing business model: Manufacturing drives much of the logistical complexity and burden at treatment centers and for manufacturers. An innovative model to consider is one where pharma out-licenses manufacturing to treatment centers. Many academic centers have the required infrastructure today and indicate interest in scaling these capabilities. A director of a cell and gene therapy lab at a CAR-T COE said, “It would be a huge benefit of not having to involve a third party since costs are lower and there are no inspectors to monitor your sites or the paperwork.” While not all treatment centers will be eligible for this model and liability and risks need to be further assessed, it could streamline logistics for some, and allow manufacturers to focus on process simplification for others.
- Invest in outpatient: Manufacturers and treatment centers recognize the urgent need to enable outpatient administration due to the financial, logistical and resourcing flexibility it would allow. Outpatient enablement is also necessary for expansion into the community but requires site investment which COVID-19 has deprioritized. Next-generation cellular therapy manufacturers may be uniquely positioned to support treatment centers and sophisticated community practices through this transition:
- Digital partnerships for post-infusion patient tracking and monitoring to enable ongoing evidence generation and swift (yet safe) discharge to the community
- Home care partnerships for home-based post-infusion follow-ups with direct and immediate connection to the treatment team
- CAR-T ambulatory care centers with fully upskilled technology and resources that can support multiple local COEs
- Transition of care support programs from treatment center to community with evidence-based guidance on protocols and outpatient use best practices
- Incorporation of telehealth, wearable tech and alternative sites of care into clinical trials to build an evidence base and systematize
The tone of the conversations that we had with CAR-T institutions during the acute crisis phase of COVID-19 were optimistic and overwhelmingly positive. Treatment centers will remain committed, but COVID-19 has magnified focus on model simplification and increased the need for manufacturers to differentiate to succeed. Pharma should embrace this moment of forced innovation by solving the unique challenges that are limiting CAR-T scalability today. As one CART-COE director said, “This is the time to put pieces in place so post-COVID, you can make up for the lost time, and truly start to revolutionize which types of institutions are willing to go through the process of starting to use these innovative therapies. The hurdle is too high today; manufacturers need to lower the bar.”