Varubi IV’s second-try FDA approval provides CINV patients with a new option

21st November 2017 (Last Updated November 21st, 2017 10:40)

The treatment of chemotherapy-induced nausea and vomiting (CINV) has improved significantly over the past two decades. The current standard of care is a three-drug regimen consisting of a neurokinin-1 receptor (NK1) receptor antagonist, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, and a corticosteroid—dexamethasone.

The treatment of chemotherapy-induced nausea and vomiting (CINV) has improved significantly over the past two decades. The current standard of care is a three-drug regimen consisting of a neurokinin-1 receptor (NK1) receptor antagonist, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, and a corticosteroid—dexamethasone.

However, CINV remains a major side effect of cancer treatment, with more than half the patients treated with emetogenic chemotherapy experiencing delayed CINV, which occurs 24–120 hours after initial treatment with chemotherapy. In September 2015 in the US and April 2017 in the EU, Tesaro received approval for Varubi (rolapitant), a new NK1 receptor antagonist to add to the growing arsenal against CINV. However, oral administration can be difficult for patients experiencing nausea and emesis, and the majority of NK1 receptor antagonists are administered intravenously in the US. On October 25, 2017, Tesaro announced the FDA approval of Varubi IV, an intravenous form of rolapitant, and aims to commence sales within Q4 2017.

Varubi IV was approved for the same indication as the oral form: for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic chemotherapy, in combination with other antiemetic agents. Approval was based on a study that demonstrated bioequivalence, consisting of 123 healthy volunteers, who were administered either a single dose of 166.5mg of IV rolapitant over 30 minutes, or 180mg of oral rolapitant. With the exception of infusion-site reactions with IV rolapitant, the safety profile of the intravenous form was consistent with the oral formulation.

The approval for Varubi IV comes after an earlier rejection by the FDA in January 2017. In a Complete Response Letter to Tesaro’s NDA, the agency requested additional information regarding the in vitro method utilized to demonstrate the comparability of the drug produced by two proposed commercial manufacturers, which were included in the New Drug Application (NDA).

Varubi and Varubi IV compete directly with Merck’s market-leading NK1 receptor antagonists, Emend (aprepitant) and Emend IV (fosaprepitant dimeglumine). Varubi’s efficacy is comparable to that of Emend, although it may offer safety benefits as it has been shown to have a lower incidence of adverse events. In addition, rolapitant is not an inhibitor or inducer of CYP3A4, which means that it has a lower risk of drug-drug reactions, allowing the dexamethasone dosing given with rolapitant to be higher. However, KOLs believe that the choice between Varubi or Emend will be mostly made on the basis of pricing.

Oral rolapitant was approved as Varuby by the European Commission in April 2017, and Tesaro commenced sales in May 2017 on a country-by-country basis. The company, however, has not indicated whether it is seeking approval for the IV form within Europe. Varubi generated $7m in US revenue for Tesaro in 2016, and this grew to $148m in worldwide revenues in the first three quarters of 2017. Overall, Varubi IV provides patients and physicians with a new option for the treatment of CINV, and is likely to increase the use of rolapitant in the US.