According to officials at the FDA, yesterday “the U.S. Food and Drug Administration granted accelerated approval for Darzalex (daratumumab) to treat patients with multiple myeloma who have received at least three prior treatments.”

I was planning to write about allo (donor) stem cell transplant statistics today. The premise? Be careful; a lot of commonly used stats aren’t always what they seem. Then yesterday daratumumab was unexpectedly approved several months early. In the face of the big news, I’m going to shelve statistical talk until later. Turns out the statistical caution applies to data about dara, too.

Most expected another immunotherapy trailblazer, elotuzumab, to be approved first. After all, elo’s been around year’s longer.Thing is, elo only works well in combination with an IMiD like Revlimid. Daratumumab has exhibited far more single agent activity, so bumping dara ahead makes sense. Way to go FDA!

FDA approves Darzalex for patients with previously treated multiple myeloma

November  16, 2015

Today the U.S. Food and Drug Administration granted accelerated approval for Darzalex (daratumumab) to treat patients with multiple myeloma who have received at least three prior treatments. Darzalex is the first monoclonal antibody approved for treating multiple myeloma.

Multiple myeloma is a form of blood cancer that occurs in infection-fighting plasma cells (a type of white blood cell) found in the bone marrow. These cancerous cells multiply, produce an abnormal protein and push out other healthy blood cells from the bone marrow. The disease may result in a weakened immune system and cause other bone or kidney problems. The National Cancer Institute estimates there will be 26,850 new cases of multiple myeloma and 11,240 related deaths in the United States this year.

“Targeting proteins that are found on the surface of cancer cells has led to the development of important oncology treatments,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “Darzalex provides another treatment option for patients with multiple myeloma who have become resistant to other therapies.”

Darzalex injection, given as an infusion, is a monoclonal antibody that works by helping certain cells in the immune system attack cancer cells.

The safety and efficacy of Darzalex were demonstrated in two open-label studies. In one study of 106 participants receiving Darzalex, 29 percent of patients experienced a complete or partial reduction in their tumor burden, which lasted for an average of 7.4 months. In the second study of 42 participants receiving Darzalex, 36 percent had a complete or partial reduction in their tumor burden.

The most common side effects of Darzalex were infusion-related reactions, fatigue, nausea, back pain, fever and cough. Darzalex may also result in low counts of infection-fighting white blood cells (lymphopenia, neutropenia, and leukopenia) or red blood cells (anemia) and low levels of blood platelets (thrombocytopenia).

Blood banks should be informed that patients are receiving Darzalex because the drug may interfere with certain tests that are done by blood banks (such as antibody screening) for patients who need a blood transfusion. Women who are pregnant should not use Darzalex, and women planning to become pregnant should use effective contraceptives during and for at least three months after treatment.

The FDA granted breakthrough designation for this application based on preliminary clinical evidence suggesting that if approved, Darzalex may offer a substantial improvement over available therapies. Darzalex also received priority review and orphan drug designations. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as tax credits, user fee waivers and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

Darzalex was approved under the agency’s accelerated approval program, which allows the approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.

Darzalex is marketed by Janssen Biotech of Horsham, Pennsylvania.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

###

GenmabThere are other companies involved in the worldwide roll out of daratumumab. This release by Genmab provides a lot more info about the drug, how it works and plans for distribution:

http://globenewswire.com/news-release/2015/11/16/787655/0/en/Genmab-Announces-U-S-FDA-Approval-of-DARZALEX-daratumumab-for-Multiple-Myeloma-and-Updates-Financial-Guidance.html

For me, they could have ended the release after the opening paragraph. I need confirmation of this, but if daratumumab (I call it “dara” for short; trade name Darzalex) was really approved under such a broad umbrella, a majority of myeloma patients already qualify to use it. Let me explain.

Most of these drug approvals point to patients being “refractory” to one or more compounds. For example, an approval might require a patient to be refractory to three other lines of therapy. That means three other myeloma drugs need to have stopped working for a doctor to prescribe the medication. That’s a lot higher bar than “to treat patients with multiple myeloma who have received at least three prior treatments.”

Maybe its semantics. If not, this means that someone who started with dex and radiation, then later adds Velcade or Revlimid, their specialist can add dara in any combination and at any time. RVD, radiation for one or more plasmacytomas,  then stem cell transplant? Bring on dara!

Broad interpretation like this is similar to Revlimid when it was approved. Here the bar was set even lower at one prior therapy. I remember arm wrestling with my insurance company to approve Rev for me when my Mayo Clinic specialist prescribed it for me back in 2007. After two “no’s,” we switched approaches, arguing that my first line of therapy was radiation and dex. It worked like a charm. Rev was approved within a week.

I have so much I’d like to explore here. We haven’t even looked at how well dara works, or it’s safety profile. And I don’t want to forget our discussion about how difficult it is to rely on statistics these days. I want to get back to David and how difficult it’s becoming to read the overall survival tea leaves.

I’ll tackle that over the weekend. Maybe I can get the myeloma statistical guru, Gary Petersen, to chime in. In the meantime, another patient savant, Danny Parker, has written an in-depth report that may turn myeloma therapy as we know it upside down. I’ve read the first two installments. It’s amazing!

Me? I’m feeling good enough to be excited by the speed at which myeloma therapy is morphing and changing. Hopefully some of us may live longer as a result.

Feel good and keep smiling! Pat