The staying power of FDA-approved oral Varubi (rolapitant) for chemotherapy-induced nausea and vomiting (CINV) should provide an edge in the marketplace, Tesaro Inc. CEO Lonnie Moulder told BioWorld Today. "Because 5HT3 receptor antagonists are so effective in the early phase of nausea and vomiting, the greatest need that exists today is for what we call the delayed phase, days two through five [after chemo]," he said. "The half-life of Varubi, approximately seven days, matches up very nicely with that." Given ahead of chemo, the drug "protects the patient over the full five-day at-risk period," he added. Varubi will be made available in the fourth quarter and an intravenous (I.V.) formulation is expected to be ready in about a year.

Pricing has not been established for the drug, a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors. To be used in combination with other anti-emetic agents, the drug is indicated specifically for the prevention of delayed CINV in adults.

CINV is induced via two key pathways: the neuropeptide substance P and the serotonin pathway, the latter blocked by serotonin subtype 3, or 5HT3 receptor antagonists, available since the early 1990s. "Virtually every patient that receives emetogenic chemotherapy does receive a 5HT3 receptor antagonist," Moulder said. "Substance P is more relevant after the first 24 hours, and is blocked at the NK-1 receptor."

Varubi enters the estimated $1 billion market with Emend (aprepitant), the NK-1 therapy from Kenilworth, N.J.-based Merck & Co. Inc., cleared by the FDA to prevent nausea for up to five days following chemotherapy. Emend sold about $553 million last year, but tablets must be administered on three consecutive days. "The durability and simplicity of Varubi stand out," Moulder said.

There's also Akynzeo (netupitant/palonosetron) for CINV, approved by the FDA last October. Palonosetron, approved earlier as Aloxi (Roche AG, Helsinn Healthcare SA), targets 5HT3 and works during the acute phase (within the first 24 hours) after the start of cancer chemotherapy. Netupitant, the new drug component of Akynzeo, takes aim at NK-1 and thus is designed to work during both the acute phase and delayed phase of chemo. Akynzeo is distributed and marketed by Eisai Inc., of Woodcliff Lake, N.J., under license from Lugano, Switzerland-based Helsinn Healthcare SA.

Here, too, Varubi has an advantage in half-life and beyond, Moulder said. "The NK-1 receptor antagonist that's contained within Akynzeo as well as Emend both have drug interactions with medications that are metabolized through the CYP3A4 pathway system," which is about 50 percent to 60 percent of all drugs. Best therapy for CINV patients includes a 5HT3 drug, an NK-1 drug and dexamethasone.

"With the other two NK-1 receptor antagonists, because of the CYP3A4 drug interactions, the dose of dexamethasone has to be adjusted, whereas with Varubi, no dose adjustment is necessary with dexamethasone or with any CYP3A4 substrate," he said.

Waltham, Mass.-based Tesaro Inc. gained rights to the drug from Miami-based Opko Health Inc. for $121 million including milestones, double-digit, tiered royalties and a 10 percent equity position in Tesaro. Rolapitant was a Schering-Plough Corp. property, but Opko scored it for just $2 million up front after Schering's 2009 merger with Merck and Co. Inc. (See BioWorld Today, Dec. 15, 2010.)

Jefferies analyst Eileen Flowers said a $15 million payment is due to Opko upon first commercial sale, amortized over nine years (about $1.7 million per year through 2023). She estimated Varubi sales of about $5 million, $44 million and $134 million for 2015, 2016 and 2017, respectively. "We currently assume U.S. blended pricing for I.V./oral Varubi of $350/chemo cycle, assuming parity pricing to Emend (given [the] oral Emend price of $450/chemo cycle and I.V. Emend price of $260/chemotherapy cycle)," she wrote in a research report.

Tesaro raised $86.3 million in its 2012 IPO to advance rolapitant. That offering was combined with an issue of 26.9 million shares of series B preferred stock, for net proceeds of $58.3 million. (See BioWorld Today, March 27, 2012.)

Also Wednesday, Merck said the supplemental new drug application for Emend was approved by the FDA, and the capsules are now OK'd for use in combination with other anti-emetic agents in patients 12 and older and patients yonger than 12 who weigh at least 30 kg (about 66 pounds) for the prevention of acute and delayed CINV, including that caused by high-dose cisplatin, as well as for the prevention of CINV associated with initial and repeat courses of moderately emetogenic chemo.

Tesaro's stock (NASDAQ:TSRO) closed Wednesday at $53.41, up $1.72.