TESARO Announces the Launch of VARUBI(TM) (Rolapitant) in the United States

• VARUBI™(rolapitant) provides extended protection for chemotherapy-induced nausea and vomiting (CINV) in the delayed phase (25-120 hours) with a single dose as part of an antiemetic regimen
• More than half of patients undergoing emetogenic chemotherapy may experience delayed CINV, even when prescribed a 5-HT₃ receptor antagonist and a corticosteroid

WALTHAM, Mass., Nov. 16, 2015 (GLOBE NEWSWIRE) -- TESARO, Inc. TSRO, an oncology-focused biopharmaceutical company, today announced that VARUBI™ (rolapitant), an NK-1 receptor antagonist, is now available in the United States. The U.S. Food and Drug Administration (FDA) approved VARUBI on Sept. 1, 2015, for use in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

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VARUBI is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, with a plasma half-life of approximately seven days. Results from all three Phase 3 trials of VARUBI demonstrated that patients receiving highly and moderately emetogenic chemotherapy agents, including platinum and anthracycline/cyclophosphamide-containing regimens, experienced a significant reduction in episodes of vomiting or use of rescue medication during the 25 to 120 hour period following chemotherapy administration. In addition, patients who received VARUBI reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy. No dosage adjustment is required for dexamethasone, a CYP3A4 substrate, when administering VARUBI. A single dose (two 90 milligram tablets) of VARUBI is to be administered approximately one to two hours prior to chemotherapy administration, in combination with a 5-HT₃ receptor antagonist and dexamethasone.

"We are proud to introduce our first product, VARUBI, for the prevention of delayed nausea and vomiting associated with cancer chemotherapy," said Lonnie Moulder, CEO of TESARO. "Many patients expect CINV to be a distressing part of chemotherapy, and their symptoms often occur outside of the clinic. As an NK-1 receptor antagonist, VARUBI works specifically to prevent CINV in the days after chemotherapy administration. By reducing the burden of delayed nausea and vomiting, we can help people who are undergoing chemotherapy spend time with their families and focus on what is most important to them."

"VARUBI represents a meaningful option in cancer supportive care, for both patients and physicians," said Lee S. Schwartzberg, M.D., F.A.C.P., executive director, West Cancer Center. "Blocking both 5-HT3 and NK-1 receptors has been shown to offer better control of nausea and vomiting than by inhibiting 5-HT3 receptors alone. Adding a single dose of VARUBI to an antiemetic regimen, including a 5-HT3 receptor antagonist and corticosteroid, may result in fewer episodes of vomiting or use of rescue medication, as well as less nausea that interferes with normal daily life in the days following chemotherapy. In addition, no dosage adjustment is required for dexamethasone, a CYP3A4 substrate, when administering VARUBI."

Just three weeks after the approval of VARUBI by the U.S. FDA, the   National Comprehensive Cancer Network (NCCN) added VARUBI to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Antiemesis Version 2.2015 as a recommended option, in combination with other antiemetic agents, for patients receiving both high emetic risk intravenous chemotherapy (HEC) and moderate emetic risk intravenous chemotherapy (MEC). Category 1, the highest level category of evidence and consensus, was granted to VARUBI for both HEC and MEC chemotherapy.

The full prescribing information for VARUBI is available at www.VarubiRx.com.

TOGETHER with TESARO™

TOGETHER with TESARO™ is a patient resource program dedicated to supporting people living with cancer. The program assists with access issues, so that patients with cancer can be free to focus on treatment goals and simply living life.  It provides a full suite of services to meet each patient's needs and individual experience. A team of access and affordability experts is available to help oncology practices and patients gain access to the medication they require. TOGETHER with TESARO will continue to evolve and grow to meet provider and patient needs.

For more information, please visit www.tesarobio.com/togetherwithtesaro or call 1-844-2TESARO (1-844-283-7276).

About Chemotherapy-Induced Nausea and Vomiting (CINV)

Chemotherapy-induced nausea and vomiting is a debilitating, yet often preventable, side effect of chemotherapy.

Up to 50% of patients undergoing highly or moderately emetogenic chemotherapy experience delayed CINV (25 to 120 hours post chemotherapy)—even when prescribed a 5-HT₃ receptor antagonist and corticosteroid.

Blocking both 5-HT₃ and NK-1 receptors has been shown to offer better control of nausea and vomiting than inhibiting 5-HT₃ receptors alone. Adding a single dose of VARUBI to an antiemetic regimen, including a 5-HT₃ receptor antagonist and corticosteroid, further improves prevention of CINV in the delayed phase following chemotherapy.

About VARUBI™

VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. NK-1 receptors are highly concentrated in the brain and bind neurokinin substance P. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by emetogenic stimuli, including certain cancer chemotherapies. A Positron Emission Tomography (PET) study with rolapitant in normal, healthy volunteers demonstrated that rolapitant crosses the blood brain barrier and occupies brain NK-1 receptors at high levels for up to 120 hours. VARUBI has a half-life of approximately seven days, which may contribute to the ability of a single dose of VARUBI to cover the entire delayed CINV phase (25-120 hours). 

An intravenous formulation of rolapitant is also being developed. TESARO licensed exclusive rights for the development, manufacture, commercialization, and distribution of VARUBI (rolapitant) from OPKO Health, Inc.

About the VARUBI (Rolapitant) Clinical Program

The superior efficacy of VARUBI was established in multiple global, randomized, well-controlled, blinded clinical trials that enrolled more than 2,500 patients. VARUBI, when administered in combination with a 5-HT₃ receptor antagonist and dexamethasone, was significantly superior to a 5-HT₃ receptor antagonist and dexamethasone in preventing delayed CINV in patients receiving either moderately or highly emetogenic chemotherapy.

The clinical profile of VARUBI in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two identical Phase 3 studies: HEC1 and HEC2. Both trials met their primary endpoint of complete response (CR) in the delayed phase (25-120 hours) of CINV and demonstrated statistical superiority of rolapitant 180 mg compared to active control (5-HT₃ receptor antagonist + dexamethasone). In HEC1, 264 patients received rolapitant 180 mg, and 262 received control. The proportion of patients achieving a CR was 72.7% vs. 58.4% (p=<0.001). In HEC2, 271 patients received rolapitant, and 273 received control. The proportion of patients achieving a CR was 70.1% vs. 61.9% (p=0.043). The most common adverse reactions (≥3%) among patients receiving cisplatin-based chemotherapy were neutropenia (9% VARUBI vs. 8% control), hiccups (5% vs. 4%), and abdominal pain (3% vs. 2%).

A Phase 3 trial was also conducted to evaluate rolapitant 180 mg compared to active control in 1,332 patients receiving anthracycline/cyclophosphamide combinations or moderately emetogenic chemotherapy regimens, including carboplatin, irinotecan, pemetrexed, oxaliplatin, and doxorubicin. This trial met its primary endpoint of CR in the delayed phase of CINV and demonstrated statistical superiority of rolapitant 180 mg compared to active control (5-HT₃ receptor antagonist + dexamethasone). The proportion of patients achieving a CR was 71.3% vs 61.6% (p=<0.001). The most common adverse reactions (≥3%) among patients receiving these chemotherapies were decreased appetite (9% VARUBI vs. 7% control), neutropenia (7% vs. 6%), dizziness (6% vs. 4%), dyspepsia (4% vs. 2%), urinary tract infection (4% vs. 3%), stomatitis (4% vs. 2%), and anemia (3% vs. 2%).

Primary data from the three Phase 3 studies have been published in Lancet Oncology. The analysis of the non-AC MEC population was presented at the 2015 annual meeting for the Multinational Association for Supportive Care in Cancer, and commentary has been provided in Nature Reviews Clinical Oncology.

Indication and Important Safety Information for VARUBI™ (Rolapitant)

Indication

VARUBI, in combination with other antiemetic agents, is indicated in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

Contraindication

VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate. A significant increase in plasma concentrations of thioridazine may result in QT prolongation and Torsades de Pointes.

Warnings and precautions

Interaction with CYP2D6 substrates with a narrow therapeutic index

• The inhibitory effect of VARUBI on CYP2D6 lasts for at least 7 days and may last longer after administration of a single dose of VARUBI.
• Avoid use of VARUBI in patients who are receiving pimozide, a CYP2D6 substrate. An increase in plasma concentrations of pimozide may result in QT prolongation.
• Monitor for adverse reactions if concomitant use of VARUBI and other CYP2D6 substrates with a narrow therapeutic index cannot be avoided.

Adverse reactions

• In patients receiving cisplatin-based, highly emetogenic chemotherapy in cycle 1, the most common adverse reactions reported at an incidence of ≥5% and a frequency greater than control were neutropenia (9% VARUBI vs 8% control) and hiccups (5% vs 4%).
• In patients receiving moderately emetogenic chemotherapy and combinations of anthracycline and cyclophosphamide in cycle 1, the most common adverse reactions reported at an incidence of ≥5% and a frequency greater than control were decreased appetite (9% VARUBI vs 7% control), neutropenia (7% vs 6%), and dizziness (6% vs 4%). 

Drug interactions

• VARUBI is an inhibitor of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Increased plasma concentrations of BCRP and P-gp substrates with a narrow therapeutic index may result in potential adverse reactions. Monitor for adverse reactions related to the concomitant drug if use with VARUBI cannot be avoided
• Avoid use of VARUBI in patients who require chronic administration of strong CYP3A4 inducers (e.g., rifampin) as significantly reduced plasma concentrations of VARUBI can decrease the efficacy of VARUBI

VARUBI is available by prescription only.

About TESARO

TESARO is an oncology-focused biopharmaceutical company devoted to providing transformative therapies to people bravely facing cancer. For more information, visit www.tesarobio.com.

Forward Looking Statements

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, among others, statements regarding the commercial availability of VARUBI in the U.S. and TESARO's plans to develop and commercialize additional therapies. Forward-looking statements in this release involve substantial risks and uncertainties that could cause our performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, any factors that could affect the availability or commercial potential of VARUBI. 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, 2014.