EXOME

all the information, none of the junk | biotech • healthcare • life sciences

Immunotherapy Safety Worries Halt Celgene Myeloma Study, Slow 5 Others

Xconomy New York — 

Amid growing concerns about the safety of a new class of cancer immunotherapy drugs when combined with other therapies to treat blood cancers, the FDA has put the brakes on another batch of clinical studies, this time run by the publicly traded biotech Celgene (NASDAQ: CELG).

Celgene said this morning that the nation’s drug regulator has halted one study completely, in multiple myeloma, and put partial brakes on five others: three in multiple myeloma, one in a type of leukemia, and one in a type of non-Hodgkin lymphoma.

Cranbury, NJ-based Celgene did not say that the FDA actions were due to problems in its studies. Instead, Celgene’s language pointed to an abundance of FDA caution stemming from three deaths in a different multiple myeloma study combining a so-called checkpoint inhibitor from Merck (NYSE: MRK) called pembrolizumab (Keytruda) with two other cancer drugs—including a Celgene product.

“The decision by the FDA was based on risks identified in other trials for an anti-PD-1 antibody, pembrolizumab, in patients with multiple myeloma in combination with immunomodulatory agents,” a statement from Celgene reads. PD-1 is one of the “checkpoint” proteins some cancers use to evade detection by the immune system.

The news comes one day after Bristol-Myers Squibb (NYSE: BMY) announced, for similar reasons, partial holds on three multiple myeloma trials involving combinations of its anti-PD-1 drug nivolumab (Opdivo) and other agents.

The success of pembrolizumab and nivolumab in several types of cancer has spurred a flood of other anti-PD-1 treatments, as well as hundreds of trials to test the new drugs in combinations to boost their effectiveness. The rush to test combinations has raised concerns among some experts in the field.

Anti-PD-1s have been approved to treat certain types of lymphoma, skin, lung, colon, kidney, bladder, and head-and-neck cancers, as well as tumors that share a common underlying genetic mutation.

They have not been approved to treat multiple myeloma, the third most common blood cancer in the U.S.

Last week, the FDA released a statement from its top drug evaluator, Janet Woodcock, to signal broader concern about the safety of checkpoint combinations to treat myeloma:

“The FDA is actively examining the data from the [pembrolizumab] trials and working directly with Merck to better understand the true cause of the safety concerns. In addition, the agency is working with sponsors of other similar cancer drugs, known as PD-1/PD-L1 inhibitors, to examine other trials in which these drugs are being studied in combination with other drugs, known as immunomodulatory agents, and in which they’re being studied in combination with other classes of drugs in hematologic malignancies.”

Celgene owns an industry-leading franchise of multiple myeloma drugs headed by lenalidomide (Revlimid), which has grown quickly this decade, hitting nearly $7 billion in sales in 2016. In the trial on full hold—which means patients currently enrolled must stop taking the treatment—Celgene is combining durvalumab (Infimzi), an anti-PD-1 drug from AstraZeneca (NYSE: AZN), with lenalidomide. In the five on partial hold—current patients may continue treatment, but no new patients may sign up—Celgene is studying durvalumab in combination with a wide range of drugs.

While the common element in each trial is AstraZeneca’s durvalumab, Celgene is responsible for the program, known as Fusion, and most of its costs. Celgene paid $450 million in 2015 for the rights to develop durvalumab in blood cancers.

Celgene shares were up 90 cents to $141.08 in late trading Thursday.

Image of multiple myeloma cells by KGH via a Creative Commons license.