New Drug Arrivals in Myeloma Treatment!
The myeloma community celebrated the accelerated approval of 3 new drugs to treat multiple myeloma in November of 2015. Lets have a detailed look on what these drugs are and how they work –
Produced by Japanese drugmaker Takeda Pharmaceuticals, Ninlaro, also called Ixazomib, is a reversible proteasome inhibitor. Proteosomes are cellular complexes that normally break down proteins. Proteosome inhibitors block this action thus blocking enzymes necessary for growth of myeloma cells.
Ninlaro has been approved in only those patients who have had at least one prior therapy. Also, it needs to be administered in combination with Revlimid (lenalidomide), and the corticosteroid drug dexamethasone.
The phase III trial on which the FDA approval was based, compared the effectiveness of Ninlaro in combination with lenalidomide and dexamethasone versus placebo in combination with lenalidomide and dexamethasone, and showed that Ninlaro successfully extended the progression free survival (PFS) of patients by 20.6 months compared to 14.7 months by the placebo arm.
Ninlaro comes in 4mg, 3mg, and 2.3 mg oral capsules to be taken at least one hour before or 2 hours after food. Although not contraindicated in any disease, most common adverse reactions include diarrhea, constipation, low blood platelets, nerve damage of the hands and feet, peripheral edema, nausea, vomiting and back pain.
Generic name Daratumumab, it is the first monoclonal antibody approved for treating myeloma. Developed by Johnson and Johnson (J&J) and Genmab and Marketed by Janssen Biotech of Horsham, Pennsylvania, it is a IgG1k antibody that targets CD38 protein present on myeloma cells and is approved to be prescribed to multiple myeloma patients who have received at least three prior therapies, including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent.
Darzalex works by helping our immune system cells attack the cancer cells by recognizing the CD38 antigen present on them.
Two open-labeled studies, which led to the FDA approval of the drug, showed 29% and 36% complete or partial reduction of tumor burden in patients treated with Darzalex.
Darzalex is contraindicated in pregnancy. Also since this drug may interfere with certain tests done by blood banks, it is imperative to inform the blood banks that patients are receiving Darzalex.
The most common side effects of Darzalex infusion-related reactions, fatigue, nausea, back pain, fever and cough and may also result in low counts of infection-fighting white blood cells, blood platelets and red blood cells.
Also called Elotuzumab and developed by collavorative efforts of Bristol Myers Squibb (BMS) and AbbVie, it is the second monoclonal antibody approved for myeloma treatment. It is an immunostimulatory IgG kappa monoclonal antibody that kills myeloma cells through antibody dependent cell cytotoxicity mechanism. Empliciti targets a glycoprotein called Signalling Lymphocytic Activation Molecule family member 7 (SLAMF7) glycoprotein, which is present on both myeloma cells as well as natural killer cells. Natural killer cells are a kind of white blood cells, which have the ability to bind to tumor cells or virus-infected cells and kill them.
Empliciti has been approved in those patients who have had 1-3 prior myeloma therapies and should be administered as a combination therapy with Revlimid (lenalidomide) and dexamethasone (ERd).
The ELOQUENT – 2 trial on which the FDA approval for Empliciti was based, found that the median progression free survival (PFS) in the group treated with Empliciti in combination with Revlimid and dexamethasone (ERd group) was 19.4 months compared to 14.9 months in the group treated with only Revlimid plus dexamethasone (Rd group). Also it was noted that the risk of disease progression or death was reduced by 30% in ERd group compared to the Rd group.
The drug is available for intravenous administration in 300mg and 400mg single dose vials. The most frequent serious adverse reactions of Empliciti are acute renal failure, anaemia, pneumonia, pyrexia, pulmonary embolism, and respiratory tract infection.
Although all these 3 drugs are going to be life prolonging for the patients with refractory disease, their cost remains a killer. Ninlaro is priced at $8,670 per four-week cycle, or $2,890 per Ninlaro capsule. According to J&J, Darzalex drug will cost $5,850 per infusion, starting out weekly and gradually moving to biweekly and monthly. The annual cost comes out to be approximately $135,550. For Empliciti, the wholesale price per vial will be $1,776 for the 300 mg vial and $2,368 for the 400 mg vial.
All powers to the drug companies, the insurance companies, the medical fraternity, and the researchers, to find out ways to lower the cost of these life saving drugs!