Patients with rare diseases From Hipper-Lindau (VHL) The disease has genetic mutations that cause benign tumors throughout the body. These tumors increase the risk of cancer, and the standard treatment is to remove them surgically. A Merck drug has cleared regulatory barriers and provided treatment options for VHL patients with cancer.
U.S. Food and Drug Administration Friday Officially recognized The drug belzutifan is used to treat adults with VHL disease and three cancers: renal cell carcinoma, central nervous system hemangioblastoma, and pancreatic neuroendocrine tumors. The drug is suitable for these cancers that require treatment but do not require immediate surgery. Merck will market the once-daily pill under the name “Welireg”. Its approval marks the return of the Kenilworth, New Jersey-based pharmaceutical giant for acquiring a drug in a $1.2 billion transaction two years ago.
According to Merck, An estimated 10,000 people in the U.S. have discovered VHL disease. People with this disease are born with VHL gene mutation, It encodes the protein key of cellular processes and is used to break down other proteins that are no longer needed. The VHL protein specifically targets hypoxia-inducible factor 2a (HIF-2a), which is a key protein that regulates genes that help the body cope with hypoxia, which is the low availability of oxygen in cells. However, in some cases, such as mutations caused by VHL disease, the VHL protein cannot function normally, thus making HIF-2a more active. This increased activity leads to protein expression, which triggers the production of red blood cell blood vessels, which can promote the growth of cancer.
Merck’s Welireg is a small molecule designed to bind to HIF-2a. Under hypoxic conditions or the VHL protein cannot function normally, the drug prevents HIF-2a’s ability to trigger activities that promote the growth of cancer cells. Welireg is the first drug approved by the FDA to work in this way.
The FDA’s decision on Welireg is based on data from an ongoing open-label clinical trial that evaluated 61 patients with VHL-related renal cell carcinoma, the most common type of kidney cancer. The patients participating in the study had other VHL-related tumors, including tumors of the central nervous system and pancreas.
Patients in clinical trials receive a 120 mg dose of the drug once a day until the disease progresses or the toxicity becomes unacceptable. The main goal is to assess the overall response rate to treatment, measured by imaging scans. According to the FDA, the overall response rate of Merck’s drug treatment was 49%. All patients who responded to treatment were followed up for at least 18 months; 56% of the responses lasted 12 months or longer, and the median time to response was 8 months.
The study also evaluated the drug in patients with other types of VHL-related tumors. Among 24 patients with measurable central nervous system tumors, the overall response rate was 63%. Among these patients, 73% had a response for 12 months or longer. Among the 12 patients with measurable pancreatic tumors, the overall response rate was 83%; 50% of these patients had responses that lasted 12 months or longer.
The most common adverse reactions of Welireg include decreased hemoglobin levels, anemia, fatigue, increased levels of muscle waste creatinine, and headaches. The FDA warned that Welireg’s anemia and hypoxia may be severe. In clinical trials, anemia was observed in 90% of patients, and grade 3 anemia was observed in 7% of patients (anemia is graded from 1 to 5, with 5 indicating death; grade 3 is considered severe). The FDA stated that patients with anemia should receive blood transfusions as needed, but it does not recommend the use of drugs that stimulate the bone marrow to produce more blood cells. The Welireg label has a black box warning to remind patients and clinicians that exposure to the drug during pregnancy can harm the fetus. The FDA recommends that patients verify their pregnancy status before starting treatment.
The FDA’s approval of Welireg was advanced about a month. The FDA’s regulatory decision target date is September 15. The approval means a big payday for supporters of the company that originally developed the drug. Belzutifan is the main drug candidate of Peloton Therapeutics. Two years ago, when the Dallas-based biotechnology company was preparing to conduct an IPO to fund phase 3 testing of renal cell cancer drugs, Merck previously acquired Peloton for US$1.2 billion.
According to the terms of the acquisition agreement, now that Welireg has received FDA approval, Peloton’s former shareholders will receive a milestone payment of $50, plus another $50 million after the first commercial sale of the drug in the United States. Merck said it expects the drug to be on the market in early September. The sales-based milestone may result in up to $1.05 billion in additional payments to Peloton’s former shareholders.
Merck is also developing Welireg as a potential treatment for renal cell carcinoma and other types of cancer. In February, the company began pairing the drug with Lenvima, a tyrosine kinase inhibitor developed by a Japanese pharmaceutical company and R&D partner Eisai, for phase 3 studies. The study is recruiting patients with kidney cancer who have previously received treatment and have spread.
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