- Oral Rolapitant New Drug Application (NDA) Submission on Track for Mid-2014
- Development Plans for Niraparib in Small Cell Lung Cancer and First-Line Ovarian Cancer Announced
CHICAGO, June 1, 2014 (GLOBE NEWSWIRE) -- TESARO, Inc. (Nasdaq:TSRO), an oncology-focused biopharmaceutical company, today announced that final results from three Phase 3 trials of rolapitant, an investigational neurokinin-1 (NK-1) receptor antagonist in development for the prevention of chemotherapy-induced nausea and vomiting (CINV), were presented today at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
"We are very pleased with these pivotal data which, along with the previously conducted Phase 2 study, will form the basis of our New Drug Application submission to the U.S. Food and Drug Administration in mid-2014," said Mary Lynne Hedley, Ph.D., president of TESARO. "Additionally, we look forward to expanding our niraparib development program to include clinical trials in the small cell lung cancer and first line ovarian cancer settings."
Phase 3 Results
The first Phase 3 study of rolapitant was an international, multicenter, randomized, double-blind, active-controlled study that enrolled 1,369 cancer patients receiving moderately emetogenic chemotherapy (MEC), approximately half of whom were receiving anthracycline-based treatment for breast cancer. Patients were randomized to receive either control, which consisted of a 5-HT3 receptor antagonist plus dexamethasone, or 200 milligrams of oral rolapitant plus control. Patients who received rolapitant had a significantly higher complete response (CR) rate, defined as no emesis and no use of rescue medication, for the primary endpoint of complete response during the delayed phase compared to control (71.3% vs. 61.6%, p<0.001). CR rates were higher for rolapitant-treated patients in the acute (83.5% vs 80.3%, p=0.143) and overall (68.6% vs. 57.8%, p<0.001) phases. The rolapitant group also achieved higher rates of complete protection, defined as no emesis, no use of rescue medication, and no significant nausea, in both the delayed (64.3% vs. 56.9%, p=0.006) and overall phases (62.0% vs. 53.2%, p=0.001). Approximately one-third of the participants (n=457/1,369) in this trial were enrolled at U.S.-based clinical sites, and a subset analysis of these patients showed that the rolapitant group had higher CR rates in the delayed (61.6% vs. 48.0%, p=0.005), acute (84.7% vs. 75.1%; p=0.012) and overall (59.3% vs. 44.1%, p=0.002) phases, in addition to higher rates of complete protection overall (54.2% vs. 39.7%, p=0.042), no significant nausea overall (68.1% vs. 58.5%, p=0.003), and no emesis overall (78.7% vs. 65.3%, p>0.001).
The second Phase 3 study of rolapitant was an international, multicenter, randomized, double-blind, active-controlled study that enrolled 532 patients receiving highly emetogenic chemotherapy (HEC), defined as regimens which contain cisplatin at a dose equal to or greater than 60 mg/m2. Patients were randomized to receive either control, which consisted of a 5-HT3 receptor antagonist plus dexamethasone, or 200 milligrams of oral rolapitant plus control. Patients who received rolapitant had a significantly higher complete response rate compared to control for the primary endpoint of CR during the delayed phase (72.7% vs. 58.4%, p<0.001), acute (83.7% vs 73.7%, p=0.005) and overall (70.1% vs. 56.5%, p=0.001) phases. Additionally, rolapitant-treated patients had a significantly higher rate of no significant nausea in the overall phase (71.6% vs. 63.0%, p=0.037). The rolapitant group also achieved higher rates of no nausea in both the delayed (53.0% vs. 41.6%, p=0.009) and overall phases (49.6% vs. 39.3%, p=0.018).
The third Phase 3 study of rolapitant was an international, multicenter, randomized, double-blind, active-controlled study that enrolled 555 patients receiving highly emetogenic chemotherapy (HEC), defined as regimens which contain cisplatin at a dose equal to or greater than 60 mg/m2. Patients were randomized to receive either control, which consisted of 5-HT3 receptor antagonist plus dexamethasone, or 200 milligrams of oral rolapitant plus control. Patients who received rolapitant had a significantly higher complete response rate compared to control for the primary endpoint of CR during the delayed phase (70.1% vs. 61.9%, p=0.043). CR rates were also higher for rolapitant-treated patients in the acute (83.4% vs 79.5%, p=0.233) and overall (67.5% vs. 60.4%, p=0.084) phases. The rolapitant group also achieved higher rates of no nausea in both the delayed (58.3% vs. 46.9%, p=0.007) and overall phases (55.0% vs. 44.0%, p=0.009).
Safety & Tolerability Data
Safety and tolerability data for patients who received rolapitant were similar to the results for those who received control in each of the three Phase 3 trials, and were consistent with the results from earlier rolapitant clinical studies. The most frequently reported treatment-related adverse events were balanced across treatment arms and included fatigue, constipation, headache, nausea, hiccups and dyspepsia.
Preparations continue in support of a submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in mid-2014. The oral rolapitant NDA will include data from one Phase 3 study in patients receiving moderately emetogenic chemotherapy (MEC), in addition to one Phase 2 and two Phase 3 trials in patients receiving cisplatin-based, highly emetogenic chemotherapy (HEC). The top-line results of each of the Phase 3 trials of rolapitant were previously announced by TESARO.
Rolapitant is an investigational agent and, as such, has not been approved by the U.S. FDA or any other regulatory agency. The p values presented above are unadjusted.
Rolapitant is a potent and selective NK-1 receptor antagonist with an extended plasma half-life that is being developed for the prevention of CINV. NK-1 receptors are highly concentrated in the brain and bind the neurokinin substance P. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by emetogenic stimuli, including certain cancer chemotherapies. NK-1 receptor antagonists have been demonstrated to improve the management of nausea and vomiting experienced by cancer patients undergoing chemotherapy. The safety and tolerability of single and repeat doses of rolapitant have been assessed in more than 2,500 healthy volunteers and patients. Rolapitant is being developed both in oral and intravenous formulations. TESARO licensed exclusive rights for the development, manufacture, commercialization and distribution of rolapitant from OPKO Health, Inc.
About Chemotherapy-Induced Nausea and Vomiting (CINV)
CINV is estimated to afflict over 70% of cancer patients undergoing chemotherapy and, if not prevented, may possibly result in a delay or even discontinuation of chemotherapy treatment. Prolonged nausea and vomiting may result in unwanted weight loss, dehydration and malnutrition, as well as hospitalization.
TESARO is an oncology-focused biopharmaceutical company dedicated to improving the lives of cancer patients by acquiring, developing and commercializing safer and more effective therapeutics. For more information, visit www.tesarobio.com.
To the extent that statements contained in this press release are not descriptions of historical facts regarding TESARO, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Examples of forward looking statements contained in this press release include our expectations regarding future clinical trials with niraparib. Forward-looking statements in this release involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the initiation of future clinical trials, availability of data from ongoing clinical trials, expectations for regulatory approvals, and other matters that could affect the availability or commercial potential of our drug candidates. TESARO undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see TESARO's Annual Report on Form 10-K for the year ended December 31, 2013 and other filings TESARO makes with the Securities and Exchange Commission.
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