According to Ryan McDonald of Cure Today, the FDA recently granted Breakthrough Therapy Designation to MK-6482, an investigational HIF-2α inhibitor developed by Merck. The orally-administered drug, designed to treat patients with VHL-associated renal cell carcinoma (RCC), blocks hypoxia-inducible factor (HIF)-2α. Normally, this plays a role in fueling kidney cell growth. However, this can be dangerous when those cells are cancerous.

According to the FDA, Breakthrough Therapy Designation is:

intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

As a result of receiving this designation, as well as Orphan Drug Designation, Merck will receive quicker regulatory review, assistance with drug development, and increased mentorship and communication with the FDA. The FDA granted both statuses following presentations at the 2020 ASCO Virtual Scientific Meeting. Within these presentations, researchers shared that MK-6482 reduced cancerous lesions or tumors in 86.9% of patients within a clinical trial.

Von Hippel-Lindau (VHL) Syndrome

Resulting from VHL gene mutations, von Hippel-Lindau (VHL) syndrome is a rare inherited disorder that causes cysts and tumors to form throughout the body. However, in 20% of cases, people with VHL have no family history of the disorder. Generally, VHL-related cysts and tumors develop in the retina, spine, kidneys, pancreas, adrenal glands, inner ear, brain, and genital tract. They can be either cancerous or benign. Regardless, VHL raises the risk of developing pancreatic neuroendocrine tumors (pNETs) and renal cell carcinoma (RCC). Around 10,000 people in the U.S. have VHL.

Symptom onset varies, but many people experience their symptoms initially in their early 20s. Symptoms and manifestations include:

• Headaches
• Issues with balance
• High blood pressure
• Digestive issues
• Excessive sweating
• Anxiety
• Vision and hearing loss
• Hemangioblastomas in the retina, spine, and brain

Learn more about VHL syndrome here.

Renal Cell Carcinoma (RCC)

Doctors aren’t exactly sure of the cause of renal cell carcinoma (RCC), an aggressive and easily spreading form of kidney cancer. In many cases, RCC begins as a singular kidney tumor. However, it often spreads to the lungs or other organs. Risk factors include smoking, a history of kidney issues, and genetics. In fact, mutated PRC, TFE3, and VHL genes are associated with RCC. The cancer usually develops between the ages of 50 and 70, and impacts males more than females.

Symptoms include:

• Bloody or rust-colored urine
• Unintended weight loss
• Vision problems
• Fatigue
• Fever
• Abdominal pain and pressure
• High blood pressure
• Enlarged testicles or testicular veins

Learn more about RCC here.