Blood disease light chain (AL) amyloidosis currently has no FDA-approved therapies, but Johnson & Johnson is making its case for Darzalex to become the first.
Adding the recently approved subcutaneous version of the drug—known as Darzalex Faspro—to a trio of chemo drug cyclophosphamide, Takeda’s Velcade and steroid dexamethasone cleared (PDF) disease from the blood in 53% of newly diagnosed AL amyloidosis patients in a phase 3 trial, J&J said Saturday at the European Hematology Association’s virtual annual congress.
Cyclophosphamide, Velcade and dexamethasone on their own, meanwhile, hit that benchmark in only 18% of patients.
The data are important, as nearly one-third of AL amyloidosis patients die within a year of diagnosis, Mark Wildgust, Ph.D., vice president of global medical affairs for oncology at J&J’s Janssen unit, said. “Once you get that diagnosis, the outcomes are quite poor for these patients,” he said, adding that “it’s quite a critical time to try to engage in treatment.”
One reason? The disease’s only symptom is organ deterioration that may take up to 10 years to show up. When it finally does, patients “present with symptoms like congestive heart failure or renal disfunction,” Wildgust noted.
Those symptoms are similar to those caused by more common ailments, so when a patient goes to a cardiologist, for example, AL amyloidosis—which affects about 4,500 patients per year in the U.S.—is not necessarily top of mind for the doctor.
“That ends up delaying patients from getting identified,” Wildgust said, adding that nearly a quarter of AL amyloidosis patients have seen more than six doctors before finally getting a diagnosis.
The makeup of J&J’s trial, called Andromeda, reflected that delay. More than two-thirds of patients had two affected organs, with 59% and 72% experiencing kidney and heart involvement, respectively.
But in addition to clearing disease at a rate nearly three times that of the standard-of-care regimen, the Darzalex-containing cocktail also delayed the time to major organ deterioration, J&J said.
“It’s not like you had this trial read out with one endpoint that was statistically positive,” Wildgust pointed out. “What we see is a broad effect of Darzalex on AL amyloidosis with that significant deep response, delaying of organ deterioration, delaying of the need for other interventional therapy and an improvement in organ response as well.”
J&J’s myeloma blockbuster is looking to become the first approved therapy in the plasma disorder after Takeda’s Ninlaro, another myeloma drug, failed a phase 3 trial in AL amyloidosis last year.
It’s also looking to cement its position as the top CD38 drug on the market after picking up some recent competition from Sanofi’s Sarclisa, a product the French pharma’s R&D chief John Reed recently said has "the potential to become the anti-CD38 of choice for the treatment of multiple myeloma.”
The amyloidosis win “just continues to add to that breadth of data we have underpinning” Darzalex as the leading drug in its class, Wildgust said, referencing “a lot of noise out there” about other companies’ rivals.