FDA OKs Bristol Myers Squibb’s LAG-3 drug, approving first new class of checkpoint inhibitor in 8 years
For the first time in nearly a decade, the FDA has approved a new type of checkpoint inhibitor to treat certain patients with cancer.
The drug, developed by Bristol Myers Squibb and known as relatlimab, is approved for patients with metastatic melanoma or melanoma that can’t be treated with surgery. It’s given in combination with Opdivo, Bristol’s blockbuster PD-1 inhibitor.
Marketed as Opdualag, the antibody combo will cost $27,389 per infusion. A Bristol spokesperson said the price is in line with other combination treatments for metastatic melanoma.
Relatlimab is notable because it has the same principle mechanism of action — known as checkpoint blockade —as blockbuster CTLA-4 and PD-1 immunotherapies, such as Yervoy and Keytruda. But it goes after a new target on T cells, called LAG-3.
It’s the first new checkpoint target to reach patients since the first PD-1 drugs were approved in 2014. Researchers hope it could be the beginning of a series of new immunotherapy targets that improve responses to and expand the use of checkpoint therapies, although they caution that the field has faced more than its share of failures in recent years.
Like the two previous class of drugs, relatlimab is designed to take the brakes off the immune system, unleashing it to attack tumors. Bristol Myers showed it could do so in a pivotal trial of 714 Stage III and Stage IV melanoma patients, notably without triggering untoward side effects.
The study randomized patients to receive either a combination of Opdivo and relatlimab or Opdivo alone. Patients who received the combination went a median of 10.1 months before their cancers progressed, compared to 4.6 months for Opdivo alone.
The progression data is similar to what researchers see when they combine Opdivo and Yervoy, Bristol Myers’ CTLA-4 inhibitor, but that combination can be highly toxic, leaving oncologists to only prescribe it for a subset of patients.
Relatlimab, though, showed comparatively few adverse events. The most common were elevated liver enzymes and fatigue, each of which occurred in just over 1% of patients.
That means oncologists can now prescribe LAG-3/PD-1 for patients who are too sick or otherwise don’t want to handle the side effects of CTLA-4. Executives and other researchers caution, though, that they will need more and longer-term data before concluding the LAG-3 combo is the new standard of care.
If future survival data for LAG-3 combo look similar to the CTLA-4 combo, it would reinforce “as the new standard of care for previously untreated patients with advanced melanoma,” two UK cancer researchers wrote in an New England Journal of Medicine editorial. “It is unlikely that there will be a head-to-head trial between the two combinations, since the difference in toxic effects is stark.”
Bristol Myers is now running additional trials testing LAG-3 in lung, colon and other cancers in hopes that it will also prove effective there. However, some experts doubt it will prove effective in many other cancer types and companies developing rival LAG-3 drugs, such as Regeneron, have concentrated their efforts on skin cancer.
“My understanding of what’s been at least publicly released is there’s not a slam dunk indication, where you get the same kick in activity, as melanoma,” Israel Lowy, Regeneron’s head of oncology, told Endpoints News in January.
Miriam Merad, head of Mount Sinai’s Precision Immunology Institute, agreed, telling Endpoints at the time: “I think it’s going to be very tumor specific.”