One of the most significant advancements made in treating disease in recent years is the development and commercialization of CAR-T therapy, which weaponizes a patient’s own white blood cells to attack certain types of blood cancer cells. For some cancer patients, CAR-T therapy hope holds the promise or a cure.
In fact, in early 2022, two cancer patients, a middle-aged man and a 16 year old who had participated in clinical trials for these novel therapies celebrated cures from the treatments they’d received a decade ago.
Since the first CAR-T therapy was approved by the Food and Drug Administration (FDA) in 2017, five more therapies have gained FDA approval for treating specific types of leukemia, lymphoma and multiple myeloma in both children and adults. Research is underway to develop similar solutions for solid tumor cancers as well.
At Cardinal Health, our experts have been involved in the research, development and logistics of CAR-T therapies since 2015, partnering with the companies that are developing them to help get the treatments to patients faster. We provide solutions across the drug development cycle, from assisting with regulatory approvals and enhancing product launch strategies, to providing logistics solutions that help ensure patients are able to get the medication they need.
In this story, we provide some basics about these therapies, take a look at what’s next in treatment options, and explore some of the ways that our Advanced Therapy Solutions help patients.
What is CAR-T therapy?
A CAR-T therapy reprograms a patient’s own cells to fight cancer. When a patient is prescribed a CAR-T treatment, specialists remove a sample of the patient’s T-cells (white blood cells) and send them to a lab where they are modified to produce proteins called chimeric antigen receptors (CARs) on their surface. The modified cells are returned to the hospital and administered back to the patient; the CARs enable the cells to find and kill cancer cells.
Developing a CAR-T therapy is complex, and unique for each patient. It requires patient referral to an accredited center (of which only ~250 exist in the U.S.), patient evaluation and consent, then t-lymphocyte collection, T-cell modification and expansion, and T-cell infusion back to the patient. Those who receive a CAR-T therapy must also undergo chemotherapy to deplete competing circulating T-cells.
Though CAR-T therapy has given new hope to many patients, it is not without health and safety risks. The most common side effect, effecting 70-90% of patients, is called cytokine release syndrome (CRS), an immune response that occurs while the modified T-cells are multiplying and attacking the cancer in the body. Some patients compare CRS to having a severe case of the flu, with high fever, fatigue and body aches. It is a serious and life-threatening side effect to treatment, requiring close monitoring by healthcare professionals, usually in an in-patient setting. Some patients may also experience a side effect called neurotoxicity, potentially life-threatening adverse events that can cause confusion, tremors, or difficulty with communication.
How CAR-T therapies are changing cancer treatment
FDA-approved CAR-T therapies can be used to treat patients who have already been through at least one unsuccessful standard treatment, such as chemotherapy or a stem cell transplant. With a success rate of about 30% to 40% for lasting remission, CAR-T treatments are the only FDA-approved therapy to show significant benefit for those patients who, as few as five years ago, had no other course of treatment. That is why, despite potentially dangerous side effects, the adoption of CAR-T therapy as a treatment continues to grow.
A recent study published in Nature shows that CAR-T treatments may be more effective that other treatments as the first treatment for the relapsed/refractory patient, rather than second-line or later. If so, this would bring new hope for patients and reduce their total time of treatment: CAR-T treatments typically take about a month, compared to the six months often required for traditional chemotherapy or stem cell transplants.
Cardinal Health Specialty Solutions’ Chief Medical Officer, Bruce Feinberg, has been conducting observational research on the perceptions, obstacles and adoption of these therapies since 2015. “When the first CAR-T therapy was launched, there was significant concern among oncologists about the toxicity of these therapies: More than 43% of oncologists surveyed said that the toxicity profile was concerning enough to limit the number of patients they would refer for this treatment. However, over time and with improved understanding of toxicity and its treatment, as well as newer CAR-T therapies that have lower toxicity profiles and the benefits of real-world evidence insights, oncologists have become less concerned about toxicity and have found that the benefits outweigh the risks in many cases.”
Obstacles to patient access
Cardinal Health researchers monitor and explore other challenges associated with CAR-T therapies. Often cited concerns about CAR-T therapies are related to costs. Priced up to $1 million per person per treatment, CAR-T therapies are some of the most expensive treatments on the market. However, our researchers are finding that the high price tag is no longer deterring oncologists as much as it did when the first CAR-T therapy was approved as evidence of the benefits of these treatments stacks up.
Beyond the sticker price, oncologists often cite the administrative burdens of using these therapies, including cumbersome logistics, long referral processes and payer approvals, as obstacles that need to be overcome.
Administrative delays often impact whether the patient will be able to receive the treatment at all. Because cancer can progress so rapidly, any delay may mean that a patient won’t get the therapy they need in time. In fact, our researchers found that 69% of oncologists surveyed cited disease progression as why patients prescribed CAR-T therapy didn’t receive it.
However, Feinberg said, “As we gain more real-world evidence of efficacy, we have seen a shift in the obstacles that are cited by oncologists, from safety to cost to cumbersome logistics, which shows the interest and adoption among the medical community as solutions to these concerns continue to evolve.”
With more than one hundred companies around the globe now developing CAR-T technologies, we anticipate continued innovation in these therapies, Feinberg said.
Something that could open more options for CAR-T treatments is a shift from autologous (unique to a single patient) to allogeneic CAR-T treatments, which are off-the-shelf options that can be used by many patients. Several pharmaceutical and biotech companies are in the process of developing these off-the-shelf products, or even beginning clinical trials on them.
Additionally, many hope that the treatments will become available in the community oncologist setting, rather than only in accredited centers, often large research hospitals, where patients often must travel for treatment. “There are still quite a few barriers to overcome before these therapies can move to the community setting,” said Feinberg. “Oncologists continue to indicate that the greatest barriers for administering CAR-T therapy in their own practice is the ability to manage acute or immediate complications. That could mean that only CAR-T therapies with lower toxicity will move to community practices.
Cardinal Health’s role in increasing patient access
By bringing together experts across the product development and commercialization life cycle, Cardinal Health’s innovative Advanced Therapy Solutions team has been instrumental in getting these therapies to patients.
Beginning with product development, our Regulatory Sciences experts consult with pharmaceutical manufacturers to facilitate FDA or other regulatory agency product approval. Our more than 200 consultants have supported the product development of 36 advanced therapies, and have worked on a variety of CAR-T therapies.
On a parallel track, our Real-World Evidence team works with manufacturers to develop regulatory-grade research for therapies intended for small patient populations. Since 2015, this team has published 20+ abstracts and manuscripts dedicated to CAR-T therapy adoption and obstacles for the biopharma and oncology communities.
Once products are approved, our Third-Party Logistics and Services team sets up standard operating procedures at sites for CAR-T products and handles therapy ordering. Since 2017, this team has processed more than 7K cell therapy orders.
Finally, once CAR-T therapies are on the market, the Cardinal Health SonexusTM Access and Patient Support team steps in, working directly with patients. They take patients’ calls, respond to questions, help with the logistics for patients to travel to sites of care, find answers to health insurance questions, and more, all to help ensure that patients can get on – and stay on – these novel therapies.
“CAR-T therapies are showing the evolution of our understanding of medicine, and how we fight and cure diseases,” Feinberg said. “In just five years, we have seen incredible adoption and utilization that I expect will continue as new CAR-Ts come to market,” said Feinberg.