Bristol-Myers Squibb's novel immune checkpoint inhibitor combination Opdualag has demonstrated impressive early market performance, generating $58 million in sales during its first quarter on the market after receiving FDA approval in March for unresectable or metastatic melanoma.
The fixed-dose combination of LAG-3 inhibitor relatlimab and PD-1 inhibitor nivolumab (Opdivo) represents the first LAG-3-targeting therapy to receive regulatory approval, giving BMS a significant first-mover advantage in this emerging class of cancer immunotherapies.
"Opdualag is off to a great start," said BMS Chief Executive Giovanni Caforio, noting that the drug has already captured low double-digit market share in first-line metastatic melanoma treatment with additional uptake in second-line settings. The early performance reinforces the company's confidence that Opdualag can meet its projected $4 billion peak sales target across multiple cancer indications.
Clinical Advantage in Melanoma Treatment
The FDA approved Opdualag based on the phase 2/3 RELATIVITY-047 trial, which demonstrated substantial clinical benefits compared to Opdivo monotherapy. Patients receiving the combination experienced a median progression-free survival of 10.1 months versus 4.6 months for Opdivo alone, more than doubling the time patients lived without disease progression.
This impressive efficacy data, coupled with a manageable safety profile, positions Opdualag as "a potential new standard of care in patients with metastatic melanoma around the world," according to Caforio. The drug is anticipated to receive European approval in the coming weeks following a positive recommendation from the EMA's human medicines committee.
While some cannibalization of Opdivo monotherapy and the Opdivo/Yervoy (ipilimumab) combination is occurring, BMS reports that the switching patterns align with expectations. Most transitions come from patients previously on PD-1 monotherapy, where the clinical benefits of Opdualag are most pronounced.
Safety Profile Advantages
Opdualag offers a potentially more tolerable alternative to the Opdivo plus Yervoy combination, which has been available for melanoma since 2015 but is associated with significant toxicity. In clinical trials, more than 50% of melanoma patients treated with Yervoy experienced grade 3/4 adverse events.
By comparison, Opdualag demonstrated a more favorable safety profile in the RELATIVITY-047 trial. Grade 3/4 drug-related adverse events occurred in 18.9% of patients receiving Opdualag compared to 9.7% with Opdivo monotherapy. Treatment discontinuation rates were 14.6% and 6.7%, respectively.
The combination is priced at approximately $27,389 per infusion after discounts, comparable to the Opdivo/Yervoy combination for melanoma.
Mechanism of Action and Competitive Landscape
LAG-3 (Lymphocyte Activation Gene-3) functions similarly to PD-1 as a negative regulator of T cells, suppressing immune activity against cancer cells. By inhibiting both LAG-3 and PD-1 simultaneously, Opdualag releases two distinct "brakes" on the immune system, enhancing its ability to recognize and attack tumor cells.
While BMS currently leads the LAG-3 inhibitor field, several competitors are advancing similar therapies:
- Merck & Co is developing favezelimab in combination with its PD-1 inhibitor Keytruda (pembrolizumab), with a phase 3 trial in colorectal cancer initiated last year
- Other companies with LAG-3 programs include Immutep (eftilagimod alpha), Novartis (leramilimab), Incyte (INCAGN 2385), and Regeneron (REGN3767)
Future Growth Prospects
Opdualag represents an important addition to BMS's portfolio as the company faces generic competition for its big-selling blood cancer therapy Revlimid (lenalidomide) and the approaching patent expiry for Yervoy. The new combination therapy helps bolster BMS's immuno-oncology franchise, which continues to be led by Opdivo and anti-thrombotic drug Eliquis (apixaban).
BMS is currently conducting additional trials of Opdualag in lung and colorectal cancers, seeking to expand the therapy's indications and fulfill its projected revenue potential. The company's overall second-quarter revenues rose 2% to $11.9 billion, with new products collectively contributing $482 million.
Among these newer therapies, beta thalassemia-associated anemia treatment Reblozyl (luspatercept) grew 34% to $172 million, while CD19-targeted CAR-T therapy Abecma (idecabtagene vicleucel) increased to $89 million from $24 million a year ago, benefiting from expanded manufacturing capacity.
As BMS continues to advance its pipeline, including the anticipated September approval of oral psoriasis therapy deucravacitinib and the progression of next-generation anti-thrombotic milvexian into phase 3 trials, Opdualag stands out as a significant innovation with the potential to transform melanoma treatment and strengthen the company's position in the competitive immuno-oncology landscape.
