The USFDA, in August this year, had accepted Genentech’s supplemental New Drug Application (sNDA) and granted Priority Review to Zelboraf (vemurafenib) for the treatment of Erdheim-Chester Disease (ECD).
It has now announced that the drug received expanded approval for the drug to include the treatment of adult patients whose cancer cells have the BRAF V600 mutation.
In its announcement, the agency explains that ECD is a slow-growing blood cancer that originates in the bone marrow. ECD causes an increased production of histiocytes, a type of white blood cell. Excess histiocytes can result in tumors infiltrating many organs and tissues throughout the body, including the heart, lungs, and brain.
Erdheim-Chester is a rare illness that results in the over-accumulation of histocytes, in tissues and organs, and can result in organ failure. There are fewer than 500 Erdheim-Chester cases in the US each year, 50 percent of whom harbor BRAF V600 mutations.
The approval, which has a breakthrough therapy designation, was based on efficacy results from the use of vemurafenib in 22 patients with BRAF V600 mutation-positive ECD. Half of these patients (11 of 22 [50%]) experienced a partial response and 1 patient (4.5%) experienced a complete response.
These data were collected as part of phase 2 VE-BASKET study, which was conducted in patients with a variety of cancers and other diseases testing positive for BRAF V600 mutations. Basket studies use an innovative clinical trial design that matches a disease’s underlying genetic profile to the mechanism of action of the medicine, instead of enrolling people primarily on the basis of their disease or its location, the company explained.
Severe side effects include the development of new cancers (skin cancer, squamous cell carcinoma or other cancers), growth of tumors in patients with BRAF wild-type melanoma, hypersensitivity reactions, severe skin reactions (such as Stevens-Johnson Syndrome and toxic epidermal necrolysis), heart abnormalities, liver damage, photosensitivity, uveitis, kidney failure, immune reactions after receiving radiation treatment, and thickening of tissue in the hands and feet.
Common side effects experienced by patients treated with the drug included joint pain, raised bumps, hair loss, fatigue, change in the heart’s electrical activity, and skin growths. Zelboraf can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception.
“The approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence. “This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with rare cancer with no approved therapies.“
