American regulators have approved Varubi (rolapitant) to prevent delayed phase chemotherapy-induced nausea and vomiting. The drug is approved for use in adults in combination with other antiemetics or drugs that prevent nausea and vomiting.
The US Food and Drug Administration (FDA) say that Varubi, a “human substance P/neurokinin-1 (NK-1) receptor antagonist,” was evaluated in three phase 3 clinical trials involving 2,800 adults.
The trials showed that when administered with granisetron and dexamethasone – a commonly used antiemetic therapy for preventing nausea and vomiting following chemotherapy – Varubi was more effective than placebo therapy during the delayed phase.
Patients given Varubi reported less vomiting and less use of rescue medication for nausea and vomiting.
The most common side effects in patients treated with Varubi included neutropenia (low white blood cell count), hiccups, reduced appetite and dizziness.
Cancer patients often experience nausea and vomiting as side effects of chemotherapy. The unpleasant symptoms can last for days after receiving therapy.
Vomiting can also cause tiredness, trouble concentrating and slow wound healing. If prolonged, more serious complications can develop that require hospitalization such as dehydration, weight loss, and malnutrition.
Chemotherapy-induced nausea and vomiting are generally categorized as acute (occurring within 24 hours of therapy) or delayed phase (persisting for up to a week after therapy). There is also another category – anticipatory – where the patient feels nauseous before treatment.
Varubi targets the delayed phase. The results of the trials show the drug led to a significant reduction in episodes of vomiting or use of rescue medication during the 25-120 hour period following administration of emetogenic chemotherapies – treatment that induces emesis or nausea and vomiting.
The trials tested Varubi with highly emetogenic (such as cisplatin and the combination of anthracycline and cyclophosphamide) and moderately emetogenic chemotherapy drugs.
“Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients’ lives and sometimes their therapy,” says Dr. Amy Egan, deputy director of the Office of Drug Evaluation III in the Center for Drug Evaluation and Research at the FDA, adding that the “approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy.”
According to the American Cancer Society, about 7 or 8 out of every 10 people treated for cancer have bouts of nausea and vomiting.
When a patient receives chemotherapy, it triggers nerve centers in various parts of the brain and the digestive system such as the esophagus or food pipe, the stomach and the intestines. These triggers activate the vomiting reflex pathway.
Antiemetics – drugs that prevent nausea and vomiting – block receptors in the vomiting reflex pathway. For example, the serotonin receptor 5-HT3, which is found in the brain and parts of the digestive system, is blocked by drugs called 5-HT3 receptor antagonists. Granisetron is one of them.
Varubi blocks another type of receptor called P/neurokinin 1 (NK-1) that is known to be particularly involved in the delayed phase of chemotherapy-induced nausea and vomiting.
The FDA note that Varubi also blocks the action of an enzyme called CYP2D6 which breaks down certain drugs. As a result, Varubi should not be given to people who are also taking the drugs that the enzyme metabolizes, such the antipsychotic thioridazine. The danger is that the amount of thioridazine in the blood may increase, which can cause abnormal heart rhythm.
Varubi is marketed by Tesaro Inc., based in Waltham, MA. CEO Lonnie Moulder says:
“Results from the phase 3 trials of Varubi demonstrated that patients receiving emetogenic chemotherapy agents, including platinum and cyclophosphamide-containing regimens, benefitted from the addition of Varubi to their antiemetic regimen.
More information about Varubi can be obtained from the company’s full prescribing information document.
Earlier this year, the FDA also approved a new daily pill for locally advanced basal cell carcinoma, an increasingly common skin cancer that occurs in the top layer of skin.