Johnson & Johnson’s Darzalex is already on track to nab a second multiple myeloma nod in newly diagnosed patients in the U.S., but its journey with England’s cost watchdog hasn't been so smooth.
In new guidance (PDF) published on Tuesday, the National Institute for Health and Care Excellence (NICE) agreed to back a multiple myeloma combo that includes Darzalex, Takeda’s Velcade and corticosteroid dexamethasone in patients who have received one previous treatment. But it didn't tap the combo for routine use; instead, it'll be covered only as part of the Cancer Drugs Fund (CDF).
NICE offered the limited coverage while citing a lack of full data on how long the combo can extend patients’ lives. The CDF offers new drugs via a managed access pathway, meaning a patient must go the extra mile and apply for its use.
As data from the phase 3 CASTOR trial shows, the three-drug regimen cut the risk of disease progression or death by 78% versus a Velcade-dexamethasone pairing. NICE recognized that staving off myeloma progression by a median 18 months was “game-changing,” but it still had several problems with the data.
For one thing, more patients in the two-drug arm, 29%, had Celgene’s Revlimid as their first treatment, while that percentage was only 12% among those in the three-drug group involving Darzalex. The CDF clinical lead argued that the difference could have favored Darzalex “because patients in this trial arm may have had a better prognosis,” even as J&J suggested some other imbalances might have negatively affected Darzalex’s performance.
What NICE was more concerned about, though, was a lack of data showing Darzalex could extend patients' lives. NICE called the overall survival data “immature,” as more than half of the patients in both arms were still alive at the company’s initial data cut after a median follow-up of 27 months. Even after J&J submitted new data with an additional nine months of follow-up, NICE wasn’t swayed, adding that it was still unable to determine the regimen’s long-term effect on survival.
This isn’t the first NICE setback Darzalex has encountered. As a monotherapy, Darzalex was first rejected for a third-line application. It is now covered in the fourth line—also only through the CDF arrangement. The reason? NICE said it didn’t have enough data to make a definite ruling on the drug’s efficacy for routine NHS use, a caveat the agency agreed to revisit in its next review in November 2020.
Last May, Darzalex—used alongside Velcade, chemo melphalan and prednisone—became the first monoclonal antibody to win an FDA green light in newly diagnosed patients. Then, at the American Society of Hematology annual meeting last December, J&J touted data showing a Darazlex-Revlimid combo could cut the risk of disease progression or death by 44%, setting the drug up for its second FDA go-ahead in previously untreated patients.