Tesaro On Track For Mid-Year NDA Filing Of Oral CINV Candidate Rolapitant

While awaiting data from the third and final Phase III trial of the oral cancer supportive care candidate, Tesaro also will advance an I.V. formulation of rolapitant. Meanwhile, PARP inhibitor niraparib is in two Phase III trials in oncology indications, with a plan to seek other tumor types the compound might treat.

Undaunted by Wall Street bearishness on the prospects for Phase III cancer supportive care candidate rolapitant, Tesaro Inc. said it remains on track to file an NDA by mid-year and begin building a commercial team that will be leveraged to support launches of other pipeline oncology candidates, notably Phase III PARP inhibitor niraparib.

During the firm’s full-year 2013 earnings call Feb. 19, CEO Lonnie Moulder called 2013 “a pivotal year for Tesaro,” noting it had produced successful data from two of three Phase III trials for rolapitant and moved niraparib into Phase III trials in ovarian cancer and breast cancer roughly a year after acquiring the candidate from Merck & Co. Inc. (Also see "Tesaro’s Niraparib Takes PARP Inhibitor Lead In Ovarian Cancer" - Pink Sheet, 25 Sep, 2013.).

For 2014, he said, the Massachusetts-based company’s goals are to get successful data from the third pivotal Phase III trial testing rolapitant in chemotherapy-induced nausea and vomiting (CINV), file an NDA for the oral formulation by mid-year, complete dose-finding testing of an intravenous formulation of rolapitant, continue advancement of the two Phase III trials of niraparib and also identify other tumor types for which that compound might be effective.

Tesaro’s plan is to launch an I.V. version of rolapitant about one year after FDA approval of the oral formulation. While 20% of the U.S. CINV market is appropriate for oral therapy, the company projects that 80%, including outpatient hospitals and clinics, will use the I.V. formulation.

“[Last December,] we reported successful top-line data for rolapitant from two completed Phase III trials,” Moulder told the call. “The product profile we now have in hand positions us well, upon approval, to penetrate the CINV market with a meaningful product for cancer patients and health care providers.”

Top-line data reported in December left some analysts suspecting rolapitant might struggle to differentiate itself from the current market standard, Merck’s Emend (aprepitant), an agent from the same drug class. With that drug slated to lose U.S. patent protection by July 2015, some observers wondered if there would be much of a market at all for a second selective neurokinin-1 (NK-1) receptor antagonist in CINV (Also see "Tesaro’s Rolapitant Hits Primary Endpoints, But Still Disappoints" - Pink Sheet, 21 Jan, 2014.).

Secondary Endpoints Unmet So Far

In a 1,369-patient study in moderately emetogenic chemotherapy (MEC), oral rolapitant met its primary endpoint, statistical significance in preventing vomiting or need for rescue medication during the “delay period” 24 to 120 hours after administration of chemo. Likewise, it met that endpoint in a 555-patient study in highly emetogenic chemo (HEC), a patient group that Tesaro projects to encompass about 10% of cancer patients. However, in neither study did the compound hit the secondary endpoints of statistically significant complete response during the first 24 hours after chemo administration or in the overall 0 to 120-hour time period after chemo infusion.

Those secondary endpoints could prove crucial in differentiation compared with Emend, analysts assert. But Moulder contends that rolapitant can be marketed effectively on the basis of efficacy, convenience and safety – the option of an I.V. formulation would only increase those potential advantages, he added. The third pivotal trial, also investigating the drug in HEC, is 95% enrolled, with results expected during the second quarter.

Tesaro envisions a potential $1.5 billion market for NK-1 receptor antagonist therapy in the U.S., based on roughly 5 million chemotherapeutic initiations annually that would be appropriate for such therapy. “Our goal is to further penetrate this existing underserved market with a product that can make a meaningful difference for patients and providers,” the CEO said. “Importantly, the oncology practice guidelines established by [the National Comprehensive Cancer Network] and [the American Society of Clinical Oncology] support significantly expanded use of NK-1 receptor antagonists for the prevention of CINV compared to current practice. Data indicate that less than 25% of this market is currently being penetrated.”

The company plans to begin building a commercial team during the late stages of FDA review of the rolapitant NDA. The U.S. commercial organization will likely number 120 associates, Moulder said, including field sales reps, medical sales liaisons, science liaisons, and marketing, reimbursement and account team support. That team then will be used to launch niraparib if approved by FDA as well, he said.

One of the more bullish analysts covering Tesaro is Leerink Partners’ Howard Liang, who maintained an “outperform” rating on its shares in a Feb. 20 note. While Moulder told the call he projects that rolapitant can be a break-even proposition for Tesaro upon reaching $55 million to $60 million in annual sales, Liang projects a fairly solid launch, with $6 million in sales in 2015, increasing to $48.6 million in 2016. He also anticipates niraparib reaching market in 2016, with first-year sales of $15.8 million.

At present, Tesaro is conducting the Phase III NOVA study of niraparib in patients with high-grade serous, platinum-sensitive ovarian cancer and the Phase III BRAVO study in breast cancer. While the firm’s goal is to continue enrolling and advancing those trials this year, it also hopes to initiate a Phase I study of niraparib in Ewing’s sarcoma by the middle of 2014.

Tesaro President Mary Lynne Hedley added that the company will seek out other tumor types in which niraparib might have a therapeutic effect, possibly including small cell and non-small cell lung cancer.

“Our strategy for niraparib will be driven by assessments of unmet need, the current standard of care and the potential use of a clinical or genetic marker to select patients for clinical trials,” she explained. “For example, sensitivity to platinum can be a predictor of PARP inhibitor sensitivity. We have the opportunity to explore a maintenance setting in certain tumor types for which platinum is used to derive an initial response because the number of courses of platinum that a patient can receive is limited by cumulative toxicity.”

Tesaro is well funded to drive these programs forward as well as its burgeoning development of Phase IIa ALK/TRK inhibitor TSR-011, in-licensed from Amgen Inc. in 2011. The firm ended the year with about $130 million in cash and equivalents on hand, and augmented that in January with a public offering of 3.2 million common shares sold at $31.50 per share, which netted $94.8 million [See Deal].