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Over the past several years, multiple myeloma treatment options have expanded widely for patients, resulting in significantly improved outcomes. The FDA approved around 16 new agents and 30 treatment regimens, transforming the multiple myeloma treatment paradigm for patients with newly diagnosed and relapsed/refractory multiple myeloma. Bristol Myers Squibb (BMS) and Janssen, a subsidiary of Johnson & Johnson, are the two titans dominating the multiple myeloma treatment market with around nine FDA-approved products for multiple myeloma in different settings.
With its industry-leading oncology portfolio, Janssen is expected to lead the multiple myeloma treatment market
Multiple myeloma treatment has advanced at a rapid pace, thanks to many new drugs hitting the market. Beyond DARZALEX, Janssen is aggressively developing its multiple myeloma franchise. DARZALEX (Janssen) and EMPLICITI (BMS) were approved at the same time (2015), but DARZALEX has grown much more quickly, touching a revenue of nearly USD 8 billion in 2022 starting from nearly USD 0.5 billion in 2016.
Several factors contributed to the continuous growth of DARZALEX and the slow uptake of EMPLICITI. DARZALEX has not stopped rolling since hitting the multiple myeloma treatment market with continuous label expansions, and the introduction of the subcutaneous formulation. DARZALEX dominates the multiple myeloma market with three front-line approvals, including one in eligible (DVTd) and two in transplant ineligible (DVMP, and DRd). While DARZALEX’s success has surged, late-stage pipeline entries of additional CD38-targeting drugs intensified competition in the busy multiple myeloma treatment market. To ward off the competition, Janssen launched the subcutaneous formulation of DARZALEX. DARZALEX Faspro cuts its dosing time to just a few minutes from hours and could help it fend off a challenge from Sanofi. Janssen has transitioned 85% of its US operations to subcutaneous formulation, while the conversion rate is at 80% in Europe. That is why, despite the growing competition, DARZALEX continues to move in the right direction, given the enhanced convenience and ease of use for the patient. DARZALEX was the first drug to receive regulatory approval in a quadruplet regimen for multiple myeloma in the first-line scenario. Another highly anticipated combination, D-RVd, is being studied in both eligible and ineligible settings for the treatment of multiple myeloma. Janssen plans to replace the RVd regimen in the earlier multiple myeloma treatment lines and shift the treatment paradigm to quadruplet regimens.
It is worth mentioning that Janssen now has five multiple myeloma medicines on the market. With this, Janssen is anticipated to dominate this decade of the multiple myeloma treatment segment. Janssen has the most diversified approved drugs portfolio, ranging from monoclonal antibodies to CAR-T’s to bispecific antibodies.
Does BMS’s reign of dominance in multiple myeloma treatment segment has come to an end?
EMPLICITI received FDA approval in the United States in 2015. EMPLICITI started with a revenue of USD 150 million and achieved a maximum revenue of USD 380 million in 2020; after that, it started to decline and registered a global revenue of USD 296 million in 2022 with an 11% decline from 2021 (USD 334 million). J&J’s DARZALEX and Takeda’s NINLARO obtained regulatory approval in 2015. Since then, DARZALEX has swiftly grown in multiple myeloma treatment segments. DARZALEX became the first monoclonal antibody to be approved for use in newly diagnosed patients. In addition, EMPLICITI also failed to make its presence in the first-line segment as the drug experienced a setback in the ELOQUENT-1 clinical trial. The addition of EMPLICITI to a regimen of Rd in transplant-ineligible did not show significant improvement in preventing disease progression compared to using Rd alone.
However, with its acquisition of Celgene in 2019, BMS took on REVLIMID and POMALYST, positioning EMPLICITI as a minor drug within a much larger multiple myeloma franchise. REVLIMID and POMALYST had a global revenue of approximately USD 9.7 billion and USD 2 billion in 2018. REVLIMID continued to deliver strong quarterly results and became one of the top-selling drugs of BMS, with a global revenue of USD 12.8 billion with USD 8.7 billion in the US. However, this was the peak of REVLIMID sales as the revenue declined afterward. The US revenues decreased by 4% in 2022 due to lower demand driven by generic erosion, partially offset by higher average net selling prices. International revenues decreased 61% in 2022 due to lower demand due to generic erosion across several European countries and Canada, lower average net selling prices, and foreign exchange impacts of 4%.
So the question is, is this game over for REVLIMID? Will the legacy of REVLIMID slowly diminish? Well, not yet. BMS is developing potential successors to REVLIMID to become the future cornerstone for multiple myeloma treatment. BMS revealed its two Cereblon E3 ligase modulators (CELMoDs) iberdomide and mezigdomide in ASH 2021. BMS is investigating these CELMoDs for multiple myeloma treatment that were intentionally designed to improve upon the demonstrated efficacy of the IMiD agents, along with manageable tolerability, ease of administration, and the potential to improve patient outcomes. These agents co-opt cereblon to induce the degradation of target proteins Ikaros and Aiolos, which inhibit tumor cell proliferation, promote tumor cell death, and induce immune-stimulatory effects.
BMS has established a comprehensive multiple myeloma treatment strategy; the company is quite optimistic about CELMoDs replacing REVLIMID in earlier lines of multiple myeloma treatment. Now, it remains to be seen whether CELMoDs can live up to such high expectations or will they be an utter disappointment. Further trials and clinical data would undoubtedly tell whether CELMoDs would become the next blockbuster.
Janssen and BMS are competing head-to-head in the BCMA CAR-T space
BMS, in partnership with Bluebird Bio, brought the first CAR-T cell therapy ABECMA, a first-in-class BCMA-directed personalized immune cell therapy delivered as a one-time infusion for triple-class exposed patients with multiple myeloma. Being the only available CAR-T therapy, the demand for ABECMA was huge, leading to supply constraints as the company struggled to meet this high demand. A year after BMS, Janssen with Legends entered into the multiple myeloma ring with the FDA approval of CARVYKTI in February 2022. J&J and Legend teamed up for the joint commercialization of CARVYKTI in the United States. The companies set the wholesale acquisition cost of CARVYKTI at USD 465,000, slightly higher than ABECMA’s initial list price of USD 419,500 upon launch.
ABECMA and CARVYKTI are in a tight race; both are approved in the fifth line in the US and fourth line in the EU and targeting earlier treatment settings with bigger multiple myeloma patient pools. ABECMA’s revenue was USD 388 million in 2022, increased by 136.6% compared to 2021; this represents a strong growth year-over-year reflecting significant patient demand and the work the company has done to increase manufacturing capacity. While CARVYKTI’s sales in Q3 and Q4 2022 remained the same with USD 55 and 54 million. Even in Q1 of 2023, ABECMA generated revenue of USD 147 million globally with USD 118 million from the US market, compared to CARVYKTI, which could generate sales of USD 72 million globally with USD 70 million from the US market only. However, sales of CARVYKTI jumped significantly from USD 72 million to USD 117 million in the 2nd quarter of 2023, which reflects improvements in supply, on the other hand, ABECMA’s sales declined to USD 132 million in Q2 from USD 147 million in Q1 2023.
In a close race with Janssen, BMS highlighted the success of ABECMA in an earlier setting with the submission of sBLA for ABECMA multiple myeloma patients who have failed two to four prior lines of therapy. Based on KarMMA-3, the FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 16, 2023. CARVYKTI still has the potential to surpass ABECMA, given that CARVYKTI was evaluated in an earlier treatment line (2L+) compared to ABECMA (3L+). CARTITUDE-4 enrolled a meaningful number of patients who had just one prior line of treatment. In June 2023, Janssen submitted the sBLA to the US FDA seeking approval for CARVYAKTI to treat adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. Based on the findings from both CAR-Ts, it appears that CARVYKTI’s advances will eventually be a barrier to ABECMA’s adoption, potentially pushing CARVYKTI to the forefront of BCMA CAR-T therapy in multiple myeloma.
Janssen obtained regulatory approval for its BCMA x CD3 bispecific antibody, TECVAYLI, for treating multiple myeloma in 2022. This addition expands the array of therapies accessible for this type of blood cancer. Janssen has reinforced its position as a leading player in the area of multiple myeloma, standing alongside Bristol Myers Squibb, with the market debut of TECVAYLI and the recent approval of TALVEY, in addition to their current drugs like DARZALEX and CARVYKTI. BMS’s another breakthrough in the multiple myeloma category is CELMoDs, which are not likely to receive regulatory approval anytime soon. With REVLIMID’s generic entry and POMALYST’s patent expiring soon, BMS has one CAR-T that might help retain the company among the top key players in multiple myeloma. However, we anticipate Janssen to be the next leader in the multiple myeloma treatment space.