Tesaro Inc. reps will be soon be hitting the prescriber/provider streets with educational and marketing messages about the value of NK-1 inhibition for chemotherapy-induced nausea and vomiting, following the approval of its oral NK-1 inhibitor Varubi (rolapitant).

FDA approved the drug for prevention of delayed-phase – 25 hours to 120 hours after treatment – for CINV, or emesis, in combination with other antiemetics on Sept. 1. Varubi may be used with initial and repeat courses of vomit-inducing (emetogenic and highly emetogenic) cancer chemotherapy.

Varubi is the third-in-class NK-1 receptor antagonist approved by FDA, after Merck & Co. Inc.’s modest-selling Emend (aprepitant), which is available in oral and intravenous formulations. The oral formulation of Emend, which is approved for acute (1-24 hours post-chemo) as well as delayed phase CINV, goes off patent this year.

The NK-1 market is under-developed, as the class is often overlooked for CINV prevention. Emend had sales of $508 million in 2013 and $553 million in 2014. An estimated 80% derives from IV use.

An intravenous formulation of Varubi is in development and will be submitted following the launch of the oral formulation.

Eisai Co. Ltd./Helsinn Group’s Akynzeo – a combination of the second generation 5-HT3 receptor antagonist palonosetron with the NK-1 antagonist netupitant in a fixed dose pill – was approved for use with the corticosteroid dexamethasone for prevention of acute and delayed nausea and vomiting associated with chemotherapy in October 2014 ([A#00141020009]). Palonostetron is marketed in injectable form as Aloxi.

Safety And Dosing Convenience

In its approval letter on Varubi, FDA said that the filing “was not referred to an FDA advisory committee because it was not the first in its class and the application” and did not raise significant public health questions. The agency did, however, issue a press release announcing the approval of the product.

Tesaro reaffirmed previously announced plans to launch in the fourth quarter. It declined to comment on price. However, in the past the company has based market projections on existing NK-1 pricing of about $450 per oral dose and approximately $300 for IV dose. Tesaro says the opportunity for the class is $1 billion to $1.5 billion in the U.S. alone; it plans to file the drug in Europe in early 2016.

The company has said that rolapitant’s selling factors include a differentiated safety profile when it comes to CYP3A4 drug interactions and its ability to be combined with any approved 5-HT3 receptor antagonist. No dosage adjustment is required for dexamethasone, a CYP3A4 substrate. Varubi also has a long half life of seven days.

NK-1 receptor antagonists have been under-used in the treatment paradigm, in contradiction with treatment guidelines, so there is an opportunity for brand sponsors to invest in education of prescribers and providers.

Patient surveys and our primary market research point to the high rate of CINV and its potentially debilitating effects, Tesaro said in a statement about the approval.

“We look forward to expanding the awareness of CINV and working with healthcare providers to make this important medicine available to patients during the fourth quarter,” the firm said.

Focus On Delayed Phase

Market research done in preparation for the launch suggests “the most compelling rolapitant messaging aligns with the area of greatest need – the delayed phase of CINV, despite use of a 5-HT3 receptor antagonist and corticosteroid treatment," CEO Lonnie Moulder said during the company’s Aug. 6 earnings call.

“We will educate oncologists and nurses about the need to fully protect at-risk patients from delayed CINV as outlined by the existing anti-emetic guidelines and we will appropriately communicate the profile of rolapitant,” Moulder told the call.

The filing was supported by three Phase III studies of 2,800 patients undergoing chemotherapy.

The trials tested Varubi with a 5-HT3 receptor antagonist and dexamethasone against just the 5-HT3/dexamethasone regimen for preventing CINV in patients receiving either moderately or highly emetogenic chemotherapy. Performance was measured by the reduction in vomiting and use of rescue medication for nausea and vomiting during the delayed phase.

A complete response in the delayed phase was the primary endpoint for all three studies, while complete response in the acute phase and overall effect (1-120 hours) were secondary endpoints.

Two studies were done with highly emetogenic chemotherapy. In these trials, the drug met the delayed phase primary endpoint. In one of the trials, it also was significantly more effective for the acute phase and overall endpoints, but in the second, it missed both secondary endpoints, disappointing the market ([A#14131224001]).

A third study tested Varubi in moderately emetogenic chemotherapy. In that trial, the drug met the primary delayed phase endpoint and also the overall secondary endpoint, but missed the acute phase secondary endpoint.

Labeling cites only the response for the primary, delayed phase endpoint.

Tesaro's Varubi: Safety, Dosing Convenience Could Drive Third NK-1 Inhibitor

More from United States

More from North America