GlaxoSmithKline has filed an NDA for casopitant, a novel NK-1 receptor antagonist to reduce nausea and vomiting in chemotherapy and post-surgical settings, the firm said May 29.

Data from Phase III trials backing the filing were presented during the American Society of Clinical Oncology meeting in Chicago May 30.

The NDA was filed during the week of May 19, GSK told "The Pink Sheet" DAILY, for a standard 10-month review. The likely PDUFA date would be around March 19, 2009.

The Anglo-U.S. pharma giant has proposed the U.S. brand name Rezonic for the compound (as well as Zunrisa for ex-U.S. marketing), and has gathered data for a single-dose regimen, as well as for three-day oral and three-day intravenous/oral regimens.

The NDA seeks indications for prophylaxis of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting, in combination therapy with GSK's Zofran (ondansetron) and dexamethasone.

Last June, GSK said it sees casopitant as an opportunity to build on Zofran, a 5-HT3 receptor antagonist, and its supportive-care franchise in oncology. During an oncology pipeline review, Debashish Roychowdhury cited a broad unmet need for CINV therapy, and predicted GSK's oncology experience and sales force would enable casopitant to find market success quickly.

While 95 percent of CINV and 60 percent of PONV patients receive prophylactic anti-emetics, Roychowdhury said, roughly 40 percent to 50 percent of those patients still experience nausea and vomiting. It is cited as the single-most important concern by such patients, he added.

Merck hit the market first with Emend (foseprepitant dimeglumine), an anti-emetic approved in capsule form in 2003. Also an NK-1 receptor antagonist, the drug was approved for PONV in June 2006, while an I.V. formulation gained a CINV indication this past January, after FDA accepted Merck's response to a May 2007 "approvable" letter (¹ Also see "FDA “Approvable” Letter Requests Validation, Stability Data For Merck’s Emend IV" - Pink Sheet, 14 May, 2007.).

Last June, Roychowdhury noted Emend had produced a 4.5 percent response in prophylaxis and predicted casopitant would prove a better therapy for CINV. GSK predicted it would be efficacious in both highly emetogenic and moderately emetogenic chemotherapy, with flexible and convenient dosing options, he said.

The NDA is backed by a pair of Phase III trials showing significant reduction in the number of patients experiencing CINV, GSK says in a release, in both HEC and MEC treatment regimens. The treatment groups received casopitant along with standard dual therapy of Zofran and dexamethasone, while the control groups received standard of care.

The HEC trial produced an 86 percent response rate in the treatment arm (p<0.0001), while="" the="" mec="" trial="" produced="" a="" 73="" percent="" response="" rate.="" complete="" response="" was="" measured="" as="" no="" vomiting="" or="" retching="" as="" well="" as="" no="" need="" for="" rescue="" medication="" for="" five="" days="" following="">

In the HEC trial, 810 patients receiving cisplatin-based chemo were randomized into two treatment groups or the control group. One treatment group received a single 150 mg tablet of casopitant along with standard of care, while the other received 90 mg of casopitant IV plus Zofran on day one and 50 mg casopitant tablets on days two and three.

Complete response was observed in 80 percent of the latter treatment group (p<0.0004), and="" in="" 66="" percent="" of="" the="" control="" group.="" the="" two="" treatment="" regimens="" produced="" response="" rates="" of="" 95="" percent="" and="" 94="" percent="" respectively="" during="" the="" first="" 24="" hours="" after="" chemo,="" and="" 86="" percent="" and="" 80="" percent="" during="" days="" two="" through="" five,="" gsk="">

A total of 1,933 breast cancer patients receiving standard MEC regimens were randomized into three treatment groups and one control group, each receiving standard Zofran and dexamethasone treatment. One treatment group received a 150 mg casopitant tablet on day one, another received a 150 mg tablet on day one plus 50 mg tablet each on days two and three, and the other received a 90 mg I.V. dose on day one and 50 mg tablets on days two and three.

Both oral dosing regimens produced a complete response rate of 73 percent, while the IV and oral regimen produced a 74 percent response, compared with 59 percent in the control arm, GSK reported.

CINV risk is greater than 90 percent for patients receiving highly emetogenic chemotherapy without prophylaxis, GSK states, while the risk ranges from 30 percent to 90 percent for patients on moderately emetogenic chemo not receiving prophylactic treatment. Episodes of CINV can have a considerable impact on quality life, even leading patients to delay or refuse therapy, the company contends.

-Joseph Haas (j.haas@elsevier.com)

GSK Files NDA For Oncology Anti-Nausea Drug

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