Health Canada Authorizes CARVYKTI® (ciltacabtagene autoleucel) for Patients with Relapsed or Refractory Multiple Myeloma Who Have Received One to Three Prior Lines of Therapy

Authorization is based on results from the Phase 3 CARTITUDE-4 (MMY3002) study, which showed treatment with CARVYKTI^® reduced the risk of disease progression or death by 74 per cent compared to standard of care.¹

TORONTO, Nov. 21, 2024 /CNW/ - Johnson & Johnson (NYSE: JNJ) announced today that Health Canada has issued a Notice of Compliance (NOC) for CARVYKTI^® (ciltacabtagene autoleucel) for the treatment of adult patients with multiple myeloma who have received one to three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide.¹ With this approval, CARVYKTI^® becomes the first and only B-cell Maturation Antigen (BCMA)-targeted therapy approved for the treatment of patients with multiple myeloma as early as second line.

CARVYKTI^® previously received a Notice of Compliance with conditions (NOC/c) from Health Canada for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and who are refractory to their last treatment.¹

Canada's Drug Agency (CDA-AMC) has recently recommended CARVYKTI^® for reimbursement with conditions for eligible patients who have received one to three prior lines of therapy. In its rationale for the recommendation, CDA-AMC pointed out that the CARTITUDE-4 trial demonstrated that treatment with CARVYKTI^®, compared to standard of care, was associated with statistically significant and clinically meaningful improvements in progression-free survival (PFS) in eligible patients. This builds on their prior recommendation for reimbursement with conditions for CARVYKTI^® in 2023 in eligible patients who have received at least three prior lines of therapy, based on the results of the CARTITUDE-1 trial. Johnson & Johnson is actively working with the pan-Canadian Pharmaceutical Alliance to negotiate reimbursement for CARVYKTI^® to enable public access.

"The new approval for CARVYKTI^® fills an important gap for patients with multiple myeloma who may require this therapy as early as first relapse and represents a significant milestone for Canadian patients with this disease," says Dr. Donna Reece*, MD, Chief Medical Officer, Canadian Myeloma Research Group. "The first approval for CARVYKTI^® was for its use in treating patients with refractory myeloma who had received at least three prior lines of therapy that included the three main drug classes (proteasome inhibitors, immunomodulatory drugs and anti-CD38 monoclonal antibodies). However, myeloma treatment options have advanced rapidly, and Canadian patients with relapsed multiple myeloma may have received all these agents in second- or even first-line treatment, and yet have not qualified for CARVYKTI^® — a highly effective immunotherapy that is transforming the treatment of multiple myeloma. This expanded indication will allow eligible patients with multiple myeloma to receive CARVYKTI^® much earlier in their treatment journey."

"The clinical trial showed that a single infusion of CARVYKTI^® significantly lowered the risk of disease progression or death compared to current standard of care," says Dr. Richard LeBlanc**, Hematologist, Maisonneuve-Rosemont Hospital. "This authorization means patients have a more effective treatment option that offers an opportunity for a deeper and durable response as early as their first relapse."

Multiple myeloma is the second most common form of blood cancer in Canada and it is estimated that 1,750 Canadians will die from the disease in 2024.^2,3 While the introduction of novel therapies in recent years has led to significant improvements in PFS and overall survival (OS) in patients with multiple myeloma, the disease remains incurable, with nearly all patients relapsing and requiring subsequent therapy.^4,5 As the disease progresses, patients experience cycles of relapse and remission, with periods of remission generally becoming progressively shorter with each new line of therapy.^6,7

"With the progressive, cyclical nature of multiple myeloma, the sooner we can give patients the treatment that is right for them, the higher the likelihood that more patients achieve better outcomes and an improved quality of life," says Martine Elias***, CEO, Myeloma Canada. "This approval offers patients hope that their next treatment will help extend remission and give them more precious quality time with their loved ones."

This latest Health Canada authorization is based on results from the Phase 3 CARTITUDE-4 study, a randomized, open-label, multicenter trial evaluating the efficacy and safety of CARVYKTI^® versus standard of care regimens of either pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent.¹ A total of 419 patients were randomized to receive CARVYKTI^® (208 patients) or standard of care (211 patients).¹ Of the patients in the standard of care arm, 183 received DPd and 28 received PVd.¹ All the patients in the CARVYKTI^® arm underwent leukapheresis and received bridging therapy.¹ At a median follow-up of 15.9 months, a 74 per cent reduction in the risk of disease progression or death (PFS Hazard Ratio [HR]=0.26; 95% Confidence Interval [CI], 0.18–0.38; p value p<0.0001) was observed in patients randomized to the CARVYKTI^® arm compared to standard of care treatments.¹

The most common nonlaboratory adverse reactions (incidence greater than 20 per cent) in CARTITUDE-4 were pyrexia, cytokine release syndrome, hypogammaglobulinemia, musculoskeletal pain, diarrhea, fatigue, upper respiratory tract infection, headache, hypotension, viral infection and nausea.¹ 

The long-term results from the Phase 3 CARTITUDE-4 study shared by Johnson & Johnson at the 2024 International Myeloma Society (IMS) Annual Meeting (Abstract #OA-65) showed a single infusion of CARVYKTI^® significantly extended OS in patients with relapsed or lenalidomide-refractory multiple myeloma who have received one to three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, reducing the risk of death by 45 per cent versus standard therapies of PVd or DPd. With these data, CARVYKTI^® is now the first and only cell therapy to improve OS versus standard therapies for patients with lenalidomide-refractory multiple myeloma as early as second line.⁸

"This milestone underscores our commitment to discovering and developing best-in-class therapies, particularly for incurable forms of cancer where patients face difficult prognoses," says Berkeley Vincent, President, Johnson & Johnson Innovative Medicine, Canada. "CARVYKTI^® plays an important role in our work to redefine multiple myeloma and ultimately help patients achieve sustained remission. We are determined to get in front of cancer and these recent regulatory and access milestones for CARVYKTI^® represent critical steps forward in reaching this goal."

About CARVYKTI^®

CARVYKTI^® (ciltacabtagene autoleucel) received a NOC/c from Health Canada in February 2023 for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and who are refractory to their last treatment.¹ An NOC/c is a form of market approval granted to a product on the basis of promising evidence of clinical effectiveness following review of the submission by Health Canada.

CARVYKTI^® was authorized by Health Canada in July 2024 for the treatment of adult patients with multiple myeloma who have received one to three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide.¹

CARVYKTI^® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA.¹ BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells.¹ The CARVYKTI^® CAR protein features two BCMA-targeting single-domain antibodies designed to confer high avidity against human BCMA.¹ Upon binding to BCMA-expressing cells, the CAR promotes T-cell, activation, expansion and elimination of target cells.¹

About the CARTITUDE-4 Study

CARTITUDE-4 (MMY3002, NCT04181827) is an international, randomized, open-label Phase 3 study evaluating the efficacy and safety of CARVYKTI^® versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).^1,9

About Johnson & Johnson

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com and https://innovativemedicine.jnj.com/canada. Follow us on LinkedIn at Johnson & Johnson Innovative Medicine, Canada and X at @JNJInnovMedCAN. Janssen Inc. is a Johnson & Johnson company.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of CARVYKTI^® (ciltacabtagene autoleucel). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither of Janssen Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

* Dr. Donna Reece was not compensated for this media work. She has been compensated previously by Janssen Inc., a Johnson & Johnson company, for other professional engagements.

** Dr. Richard LeBlanc was not compensated for this media work. He has been compensated previously by Janssen Inc., a Johnson & Johnson company, for other professional engagements.

*** Martine Elias was not compensated for this media work. She has been compensated previously by Janssen Inc., a Johnson & Johnson company, for other professional engagements. Janssen Inc. has also previously compensated Myeloma Canada for other initiatives.

© Johnson & Johnson and its affiliates 2024

	_________________________________________
	^1 CARVYKTI^®Product Monograph, Toronto, ON: Janssen Inc. July 19, 2024.
	^2 Myeloma Canada. What is Myeloma? Available at: https://myeloma.ca/recently-diagnosed/what-is-myeloma/
	^3 Canadian Cancer Society. Multiple myeloma statistics. Available at: https://cancer.ca/en/cancer-information/cancer-types/multiple-myeloma/statistics
	^4 Sonneveld, Pieter. "Management of multiple myeloma in the relapsed/refractory patient." Hematology. American Society of Hematology. Education Program vol. 2017,1 (2017): 508-517. doi:10.1182/asheducation-2017.1.508. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142583/
	^5 Bonello, Francesca et al. "Moving Toward Continuous Therapy in Multiple Myeloma." Clinical hematology international vol. 1,4 189-200. 12 Nov. 2019, doi:10.2991/chi.d.191101.001. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432368/
	^6 Yong, Kwee et al. "Multiple myeloma: patient outcomes in real-world practice." British journal of haematology vol. 175,2 (2016): 252-264. doi:10.1111/bjh.14213. Available at: https://pubmed.ncbi.nlm.nih.gov/27411022/
	^7 Karthik Ramasamy, Francesca Gay, Katja Weisel, Sonja Zweegman, Maria Victoria Mateos, Paul Richardson.
	Improving outcomes for patients with relapsed multiple myeloma: Challenges and considerations of current and emerging treatment options. Blood Reviews, Volume 49, 2021, 100808, ISSN 0268-960X. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0268960X2100014X
	^8 Mateos, et al. Overall Survival (OS) With Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care (SoC) in Lenalidomide (Len)-Refractory Multiple Myeloma (MM): Phase 3 CARTITUDE-4 Study Update. International Myeloma Society 2024 Annual Meeting. September 2024.
	^9 ClinicalTrials.Gov. A study comparing JNJ-68284528, a CAR-T therapy directed against B-cell maturation antigen (BCMA), versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in participants with relapsed and lenalidomide-refractory multiple myeloma (CARTITUDE-4). Available at: https://www.clinicaltrials.gov/study/NCT04181827

SOURCE Janssen Inc.

Media contact: Ali Aziz, [email protected], 647-978-2000; Investor contact: Lauren Johnson, [email protected]