With its Feb. 28 approval, the Janssen Pharmaceutical Companies of Johnson & Johnson and Legend Biotech USA, Inc.’s Carvykti (ciltacabtagene autoleucel; cilta-cel) becomes the second chimeric antigen receptor T-cell (CAR-T) therapy to treat multiple myeloma. Payers report being less likely to prefer it over some or all other multiple myeloma treatments with a similar indication, but oncologists are showing more enthusiasm for prescribing the new agent, according to Zitter Insights.
The FDA approved Carvykti for the treatment of adults with relapsed or refractory multiple myeloma after at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. The product is a B-cell maturation antigen (BCMA)-directed CAR-T agent. The one-time treatment will have a phased launch and will be available through a limited network of certified treatment centers. The FDA gave the drug breakthrough therapy and orphan drug designations. The therapy’s wholesale acquisition cost is $465,000.
The FDA approved the first BCMA-directed CAR-T on March 26, 2021 — Bristol Myers Squibb and bluebird bio, Inc.’s Abecma (idecabtagene vicleucel) — for the same indication as Carvykti. The agency also gave the drug breakthrough therapy and orphan drug designations. The price for the one-time dose is $419,500.
For the Managed Care Oncology Index: Q3 2021, between Aug. 23, 2021, and Oct. 11, 2021, Zitter Insights polled 41 commercial payers covering 113.8 million lives. Those with almost 40% of lives said they were likely to manage Carvykti at parity with other fifth-line multiple myeloma agents (see chart, p. 3). Abecma was cited as the treatment that payers were likely to prefer it over.
Zitter Insights and AIS Health are both MMIT companies.
The company also surveyed 100 oncologists during the same time frame. Almost 50% said they were likely to prescribe Carvykti over some other fifth-line multiple myeloma treatments, citing GSK’s Blenrep (belantamab mafodotin-blmf), Karyopharm Therapeutics’ Xpovio (selinexor), Oncopeptides’ Pepaxto (melphalan flufenamide) — which the company voluntarily withdrew from the U.S. market in October and then rescinded the withdrawal in January — and Abecma as the products most likely to be prescribed over. And 43% of respondents said they likely would prescribe it over all other similar treatments for the condition.
In multiple myeloma, payers “will typically utilize their hematology/oncology specialists and provider network to clinically manage multiple myeloma patients,” says Dea Belazi, Pharm.D., M.P.H., president and CEO of AscellaHealth. “Multiple treatment options exist, including surgery, radiation, stem cell transplant and drug therapies. For drug therapies, payers will typically utilize prior authorization to ensure that the appropriate therapy is available to the physician for their patient based upon the current clinical condition and stage of multiple myeloma.”
The choice of treatment for relapsed or refractory patients “is based on the response to drugs used in prior lines of therapy, prior adverse events and the condition of the patient,” explains Lynn Nishida, R.Ph., head of clinical operations at Evio. “Due to the selection of resistant clones at each prior line of therapy, the difficulty in achieving a response increases, and remissions tend to be shorter.”
Carvykti’s approval “brings an additional treatment option for adult patients with relapsed or refractory multiple myeloma who have failed four or more prior lines of therapy,” asserts Belazi*. “*The available clinical data from the CARITUDE-1 study appears to indicate that it may provide a potential advantage compared to other available fourth lines of therapy.”
“Carvykti will largely complete with Abecma,” says Nishida. Both are CAR-T therapies targeting BCMA, “a cell surface protein widely expressed on malignant plasma cells.” In addition, both agents “have shown high response rates and improvements in progression-free survival and overall survival that compare favorably with other available drug treatments.” She notes that both have been studied in the third-line setting, and that Janssen and Legend had sought a fourth-line indication for Carvykti but were given a fifth-line approval.
Although Carvykti and Abecma have not undergone head-to-head trials, “Carvykti has demonstrated a higher response rate than Abecma but has had a higher rate of cytokine release syndrome (CRS) and treatment-related patient deaths,” says Nishida. As with all CAR-T therapies, concerns include “durability of response, safety, and overall cost,” she says.
Production Capacity May Be Advantage
Belazi and Nishida both point out that Carvykti has a potential advantage over Abecma tied to its manufacturing. Carvykti may “provide improvements in production capacity compared” with Abecma, “which is having difficulties in meeting current demand,” says Belazi. “However, there will be a limited network of certified treatment centers as Janssen and Legend Biotech bring their production up to capacity.” Specifically, Nishida explains, “in the first year of the Abecma launch, BMS has not been fully able to meet demand for the product mainly due to a shortage of viral vectors, which are used to deliver the cell therapy.”
Bristol Myers is working on resolving those issues by the end of this year or early next year, she says. “However, until vector availability concerns are completely addressed, prescribers may likely base selection for ‘eligible patients’ [on the therapy] that has the best availability at the time it is needed, regardless of any clinical differences between Abecma and Carvykti.”
“The significance of an additional therapy option is based upon the effectiveness of the therapy in the disease treatment paradigm, product safety and how well the therapy compares to other available therapies, including other CAR-T therapies,” maintains Belazi. Approval in the fifth-line setting for Carvykti “will limit the significance of the product as it is initially market available.…The significance of this second CAR-T therapy will be in the current follow-on clinical studies, which are evaluating the product earlier in the treatment paradigm for multiple myeloma patients who have received one to three lines of prior therapy. If these trials demonstrate improved safety, clinical efficacy and duration of sustained clinical effect, this may alter the treatment paradigm.”
He tells AIS Health that while “at first glance,” another fifth-line treatment may not seem significant, “the potential significance of this new therapy option lies in the results from the Phase I/II clinical trial CARTITUDE-1.” In that study, 74% of the patients “reached the two-year survival mark, and approximately 60% of the patients did not experience any disease progression for at least two years. In addition to a 98% objective response rate and a 78% complete response rate, the study demonstrated almost a 22-month median duration of response. With a typical five-year survival rate for diagnosed multiple myeloma patients of 54%, this may provide an important therapy option for those patients in that it may provide a durability of response over time.” In comparison, Abecma “indicates a tumor response rate of 72% and 28% for complete tumor eradication, with a median time without tumor progression of slightly less than nine months.”
These “promising” results for Carvykti, however, “must be balanced with the safety profile,” which saw 95% of patients experiencing CRS, 26% suffering neurotoxicity and 23% experiencing immune effector cell-associated neurotoxicity syndrome (ICANS). Carvykti is available only through a Risk Evaluation and Mitigation Strategy (REMS) program — as is Abecma — that “will require infusion at certified facilities with health care providers trained to manage these adverse effects,” explains Belazi.
He points out that “Carvykti is priced at a 10% premium over Abecma,” which likely is due to “the potential enhanced efficacy and the longer duration of response seen in the Carvykti clinical trial while using Abecma as a comparator. The higher cost for Carvykti will be seen as a disadvantage until further clinical studies can be conducted to determine if one of these CAR-T therapies demonstrates an enhanced efficacy or safety profile or if further clinical information becomes available. Even though Carvykti is more costly than Abecma, the cost for either therapy is prohibitively expensive, and the ultimate determination for product positioning will be based on the continued clinical trials, open label extension results and additional trials for use earlier in the multiple myeloma treatment paradigm.”
Will Payers Prefer One CAR-T Over Other?
Asked if payers may prefer either Carvykti or Abecma over the other, Nishida replies that “a lot will depend on how payers can uniquely work with manufacturers and/or other vendors to mitigate both the drug’s high cost and differential cost difference. Payers are also looking at ways outside of standard rebate contracts for other methods to lower the cost, including ways to work with manufacturers to place warranties on a drug’s efficacy and safety. Product manufacturers who are willing to place their best foot forward in structuring fair types of risk-based agreements may have more influence with payers.”
When it comes to the CAR-Ts in general, payers usually have prior authorization in place, with criteria including clinical information and studies, national guidelines such as those from the American Society of Clinical Oncology and the National Comprehensive Cancer Network, “compendia recommendations, clinician input and independent value determinations” from organizations such as the Professional Society for Health Economics and Outcomes Research (ISPOR) and the U.K.s’ National Institute for Health and Care Excellence (NICE), states Belazi. “Reimbursement methodologies include using pre-negotiated pricing with manufacturers and specialty pharmacies; value-based agreements; loan-based assistance programs, which offer a payment-over-time model; site-of-care direction; and professional service administration agreements. The goal of the various reimbursement methodologies is to minimize all the costs of care and administration for the delivery of services.”
by Angela Maas