Navigating the Complex Landscape of Cell and Gene Therapy: Challenges and Solutions

There are a host of challenges when it comes to cell therapies, explained Zahra Mahmoudjafari, PharmD, BCOP, clinical pharmacy manager at University of Kansas Health System, during a presentation at the Oncology Pharmacists Connect (OPC) meeting in Austin, Texas. However, the uptake in awareness of the impact of these challenges seems to have been somewhat slow within the oncology community, according to Mahmoudjafari.

“I feel like sometimes I'm a doomsday prepper because I’m just screaming from the rooftops in terms of the pipeline, and not many people have necessarily paid attention until recently—I don't know how many approvals it took [for them to notice]. But here we are,” Mahmoudjafari said.

For cell and gene therapies, there are several classes of therapies, including new target molecules, bispecifics, gene editing with CRISPR technology, and costimulatory domains in various targets, Mahmoudjafari explained.

For cell and gene therapies, there are several classes of therapies, including new target molecules, bispecifics, gene editing with CRISPR technology, and costimulatory domains in various targets. Image Credit: © pinkeyes - stock.adobe.com

“Costimulatory domains…are very exciting and have come up with very important and improved response rates for our relapsed/refractory patients, and it continues to move up into earlier lines of care,” Mahmoudjafari said. “There's a lot going on in the pipeline with cell and gene therapies.”

For the most part, CAR T-cell therapies have been accessible for patients from academic centers, but there has been growth in adoption in the community setting as well, Mahmoudjafari explained. Adoption and accessibility for bispecifics has also been difficult, despite the operationalization of bispecifics being a broadly discussed topic in the field for some time, Mahmoudjafari noted.

“But it feels like every other day [the] FDA—who often works on Friday nights—will come up with another indication for one of these CAR T-cells, and we've got indications in lymphomas, multiple myeloma—you name it, we're seeing approvals,” Mahmoudjafari said. “It's great to have this pipeline, but not all centers have access to every single one of these CAR T-cell therapies.”

For both bispecifics and CAR T-cell therapies, most of the approved therapies require some form of observation in an inpatient acute care unit, Mahmoudjafari explained. “Although if you talk to some [cancer centers], people are doing this outpatient routinely, for those centers that are well-equipped and have the appropriate monitoring parameters in place. [With these therapies,] we’re still having the [cytokine release syndrome] and neurotoxicity concerns in long-term management, [which] we're becoming far more familiar with,” Mahmoudjafari said.

For CAR T-cell therapy, Mahmoudjafari noted that the process of development is a journey in and of itself that can take several weeks, if not months, depending on the patient and their indication.

“It's quite the journey of a prolonged manufacturing time,” Mahmoudjafari said. “And patients may not have that kind of time.”

To ensure appropriate access to cell and gene therapies for patients, there are many individuals and stakeholders involved, Mahmoudjafari explained. When patients receive these therapies in an acute care setting, oncology pharmacists will work within a multidisciplinary care team, which can include physicians, nurses, regulatory team members, quality team members, or financial counselors, as well as others.

“There's a whole village of people that are involved in ensuring that cell therapies are successful in an organization,” Mahmoudjafari said. “When cell therapies were first approved, it threw a wrench in how we were going to go about getting [prior] authorizations [PAs]. Bispecifics are actually the most straightforward [in that] you have a patient, you look for an authorization pre-certification, and then you're able to treat the patient. [But] that's not necessarily the case with CAR T, even 6 or 7 years [after the first CAR T-cell approval by the FDA].”

With CAR T-cell therapies, Mahmoudjafari explained that the PA process can take several weeks, if not longer if a payer is less familiar with the therapy. “But at this point, they're pretty familiar. It's not taking quite as long, but it can still take time,” Mahmoudjafari said.

Although challenges continue to exist around PAs, cost has been the primary issue gaining attention in relation to cell and gene therapy challenges, according to Mahmoudjafari. With CAR T-cell therapies, the total cost can range anywhere between $1 million and $2 million per patient, Mahmoudjafari explained.

There can also be significant ancillary costs with cell and gene therapies. With CAR T-cell therapies, treatment often requires a long intensive care unit admission, with potential follow up travel, lodging, and other out of pocket costs.

“These costs all add up. On the one hand, you'd say, ‘Okay, the one and done CAR T is a great option. Let's be done—it's just a million dollars, fine. What about bispecifics. It's going to cost less, right?’ Well, that's not necessarily the case,” Mahmoudjafari said. “If you really crunch the numbers, you could very easily have a comparable total cost of care when it comes to the bispecifics, because oftentimes, they are not necessarily a time-limited therapy, and they can continue on for as long as the patient is responding. These bispecifics can be very comparable, if not more expensive, depending on the primary disease state.”

However, reimbursement for CAR T-cell therapies has improved significantly since the first FDA approval for a CAR T in August 2017, according to Mahmoudjafari. This is particularly the case for commercial and managed care, as well as for Medicare.

“For CAR T, in commercial plans, most of the time, it's either a single case agreement or a global case agreement. Usually that's defined in terms of events, whether that be your admission time, your follow up time, inpatient, or outpatient,” Mahmoudjafari said. “Oftentimes, the product…requires a clinical authorization and your managed care team will work through a single case agreement, if you don't already have a global contract in place.”

For Medicare, there are diagnosis related groups (DRGs), which did not exist when the first CAR T-cell therapy was approved in 2017. “That was a very significant challenge within the cell therapy space. Every year, we reevaluate it and this DRG does change, but not by a whole lot,” Mahmoudjafari said.

Currently, however, one of the biggest barriers beyond access is payer challenges, Mahmoudjafari explained.

“Single case agreements are not going to be tenable long term as we make sure that more patients are able to receive these therapies,” Mahmoudjafari said. “They take time from an institutional perspective, and it's just not going to be sustainable. Then, what we're working toward is the Center of Excellence model. On the one hand, that sounds wonderful, but on the other hand, it can cause issues with access because of distance between centers of excellence and patients, which may require a patient to travel rather than going to their home organization.”

Additionally, another challenge is bundled reimbursement models, which can significantly vary, Mahmoudjafari explained. However, there is a lot of activity on the horizon looking to mitigate some of these challenges. “Those include risk management approaches, and you'll see more risk management and outcomes-based agreements from what we've seen with the gene therapies,” Mahmoudjafari said. “I really would love to have more outcome-based agreements with some type of warranty that these products will work, maybe with some annuity-based contracts, and lots of contract negotiations.”

Additionally, there may be an increased role for specialty pharmacies in the cell and gene therapy space. “It's very new. So, we'll see what the potential challenges are [that arise] related to this,” Mahmoudjafari said.

When it comes to ensuring appropriate access, Mahmoudjafari explained that the typical statistic discussed for patients with lymphoma is that only 2 out of 10 patients have access to cell therapies, which have moved up to the second line of care.

“That [rate of access] is just not good enough,” Mahmoudjafari said. “Impeding access causes these preventable delays, which prevents eligible patients from receiving the best possible outcome. We know that there are sociodemographic factors that are associated with this, and potentially disparities in our patient outcomes. Again, there's a lot that goes into ensuring appropriate access and affordability, and we have a lot of work to do when it comes to education and training.”

REFERENCE

Mahmoudjafari Z. Springboarding Excellence: Cultivating Innovative Solutions in Cellular Therapy. Oncology Pharmacists Connect; June 20-21; Austin, Texas.