FDA Approval Makes Breyanzi Third CAR-T Therapy in Non-Hodgkin’s Lymphoma

With the FDA’s approval of Bristol Myers Squibb’s (BMS) Breyanzi (lisocabtagene maraleucel) last month, there are now three chimeric antigen receptor T cell (CAR-T) therapies to treat a certain type of non-Hodgkin’s lymphoma (NHL). A Zitter Insights poll shows that payers do not anticipate its approval as having much of an impact on their management of the space. However, with more of these therapies in the pipeline, payers should take a closer look at these products and their strategies to manage them, say industry experts.

On Feb. 5, the FDA approved Breyanzi for the treatment of adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma not otherwise specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma and follicular lymphoma grade 3B. The agency gave the CD19-directed CAR-T therapy orphan drug, regenerative medicine advanced therapy and breakthrough therapy designations.

CAR-Ts are one-time treatments that consist of extracting a person’s white blood cells, reprogramming them to recognize and attack the cancer cells and then reinfusing them into the patient. As of early March, Breyanzi’s website listed 23 authorized treatment centers across the U.S. BMS plans to manufacture Breyanzi at its Bothell, Wash., facility.

Breyanzi — previously known as liso-cel, the shortened version of its non-proprietary name — joins Novartis Pharmaceuticals Corp.’s Kymriah (tisagenlecleucel), first approved in August 2017, and Yescarta (axicabtagene ciloleucel) from Gilead Sciences Inc. unit Kite Pharma, Inc., approved in October 2017, as the three CAR-T therapies in NHL. Kymriah also is approved to treat people up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, and Yescarta is also indicated for adults with relapsed/refractory follicular lymphoma after at least two lines of treatment.

“We never would have dreamed about five or six years ago that there would be competition in the space,” said Lynn Nishida, R.Ph., chief pharmacy officer and managing partner at Trend HealthCare Partners, during a Feb. 11 webinar. But now “we have even more options using this highly complex technology.”

For the Managed Care Oncology Index: Q2 2020, between June 1, 2020, and June 30, 2020, Zitter Insights polled 51 commercial payers with 129.6 million covered lives. Those with 96% of lives anticipated that they would manage Breyanzi to label. Asked how impactful its introduction into NHL would be for their management of the indication, payers with 71% of lives said it would have either no impact or minimal impact, while 28% said it would have a moderate impact.

AIS Health and Zitter Insights are both MMIT companies.

Payers said that Breyanzi would need to have a 15% to 16% reduction in its wholesale acquisition cost from the WACs of the other two CAR-Ts for members to have access to the new agent. Breyanzi launched with a list price of $410,300 for the one-time treatment compared with $373,000 for Yescarta and Kymriah in NHL. The price for Kymriah in ALL is $475,000.

In response to a question about the new drug’s price, Kimberly Whitefield, director of worldwide cell therapy communications at BMS, tells AIS Health that “Breyanzi is a potentially definitive treatment with a differentiated safety and efficacy profile for R/R LBCL [i.e., relapsed/refractory large B-cell lymphoma] that addresses an unmet need by offering an individualized treatment experience for patients and HCPs [i.e., health care professionals]. Breyanzi can be administered in the inpatient or outpatient setting of a certified health care facility and has demonstrated sustained response. BMS believes Breyanzi delivers significant value including medical value, patient value and overall impact to the health care system. BMS prices our therapies based on the value they deliver. In setting the price for this new treatment, we considered many factors to ensure responsible pricing that strikes a balance between ensuring access for every eligible patient who may benefit and rewarding medical innovation and investment in research and development.”

Will Competition Result In Price Erosion?

“All three CAR-T therapies have the same approved indication for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy,” points out Winston Wong, Pharm.D., president of W-Squared Group. “One would think that this would lead to increased competition for the lymphoma indication, leading to the potential ability for payers to negotiate net pricing. I believe the reality is that unless the managed care organization has a pathway program in place, there will be few organizations that will manage the selection of any of the CAR-T agents for the lymphoma indication. Only those organizations with a pathway program in place will truly manage the class. Since efficacy and safety appear to be similar across the three CAR-T agents, it will come down to cost. Perhaps with three CAR-Ts on the market for the same indication, one can only hope to see some price erosion.”

BMS is not offering outcomes-based contracts at this time, Whitefield says, but it does offer programs and resources for patients and their caregivers, including “copay assistance for patients with commercial/private insurance, a patient assistance program for eligible patients with financial need who are uninsured or have insurance that excludes coverage for [the] CAR-T cell therapy product and assistance for eligible patients with financial need who must relocate to comply with safety monitoring requirements.”

Providers May Drive CAR-T Choice

Wong tells AIS Health that “it is my expectation that the oncology practice will be the deciding party to choose a preferred CAR-T, based upon experience and cost to the practice.”

Zitter Insights also polled 102 oncologists between June 1, 2020, and June 30, 2020. Approximately half said they did not anticipate administering Breyanzi, slightly more than those with the same response for Yescarta and Kymriah (see chart below). Of oncologists administering the CAR-Ts, more expected to do so in an inpatient setting as opposed to an outpatient one. One of the reasons for hesitancy over outpatient infusion is the products’ side effect profile. The labels for all three therapies contain black-box warnings for neurologic toxicities and cytokine release syndrome (CRS), a potentially fatal reaction that is treated with Actemra (tocilizumab) from Roche Group member Genentech USA, Inc.

Asked how payers can distinguish among the CAR-Ts, Wong responds that “most payers will have medical policies in place that will state that the medication is to be used for its approved label. Due to the complexity of the CAR-T administration, as well as administration in a certified facility, payers will be most likely aware of the utilization of any of the CAR-T agents, but this will mainly be from a contracting standpoint as opposed to the promotion of a preferred product.”

BMS says it can turn around a dose of the product within 24 days. That’s slightly more than the other two CAR-Ts, which may be a “disadvantage” for Breyanzi, said Nishida during the webinar: Kymriah takes 22 days, and Yescarta takes 17 days. Clinical trials showed a complete remission rate of 54% for people treated with Breyanzi, “which is on par” with Yescarta, she said, and Kymriah for the same indication has a 64% remission rate. All three therapies require that patients are monitored closely for a period of time after infusion, with the requirement that patients remain near the treatment facility for a period of time.

For the first week following infusion with Breyanzi, patients will be monitored daily, which may be done in person or remotely, and then must stay “within proximity” of the health care facility for at least four weeks after infusion, says Whitefield. BMS is providing Cell Therapy 360, “a digital service platform that optimizes access to relevant resources which are designed to support patients and caregivers through the Bristol Myers Squibb CAR-T cell therapy journey, from enrollment through the initial post-infusion monitoring period. The platform includes outpatient monitoring support. BMS will also offer patients disposable wearable technology during the initial post-infusion monitoring period, which will help them track their temperature in real-time through a smartphone.”

Asked how BMS will conduct long-term patient monitoring, Whitefield says that both long- and short-term care “will vary by patient.…Supportive care or treatment may be required to manage CRS, neurologic events or other potential adverse events following treatment with Breyanzi. As part of the 15-year follow-up registry study, patients who receive Breyanzi will require long-term monitoring in order to characterize the long-term safety profile of Breyanzi in the post-marketing setting. In addition, lifelong monitoring should be conducted to identify potential secondary malignancies.”

Payer preparation for these treatments cannot come too quickly, with FDA decisions on more CAR-Ts expected soon. Nishida pointed out that a decision on BMS’s multiple myeloma therapy idecabtagene vicleucel could come by the end of this month. Another multiple myeloma treatment, Johnson & Johnson’s citacabtagene autoleucel, has a decision expected in the second half of this year.

“Regardless of the high price, it just really spells out how payers need to be prepared to address these high-cost products for the rare few who have little options left, but they could potentially benefit from these products,” said Nishida.

For more information on the Zitter data, contact Jill Brown Kettler at jbrown@aishealth.com. Contact Nishida at Lynn.Nishida@TrendHCP.com, Whitefield at Kimberly.Whitefield@bms.com and Wong at w2sqgroup@gmail.com.

This story was reprinted from AIS Health’s monthly publication RADAR on Specialty Pharmacy. Visit
https://aishealth.com/product/specialty-pharmacy.

Angela Maas

Angela has an extensive background of editing, reporting and writing for trade and consumer publications. She has written Radar on Specialty Pharmacy (formerly called Specialty Pharmacy News) since she joined AIS Health in 2005 and has broad knowledge of the various issues at play within the space. Before joining AIS Health, she was managing editor at Employee Benefit News and Employee Benefit News Canada and managing editor at HemAware (a hemophilia publication), Lupus Living and Momentum (a multiple sclerosis publication). She has a B.A. in English and an M.A. in British literature from Arizona State University.

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