New Preliminary Data from Two Studies Show Clinical Activity of Neratinib in Combination with Trastuzumab and in Combination with Paclitaxel in Advanced HER-2 Positive Breast Cancer
Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), todayannounced preliminary data from two ongoing studies, one evaluatingneratinib (HKI-272) in combination with trastuzumab (Herceptin(R),Roche) in HER-2 positive (ErbB-2 positive) breast cancer, and aseparate study investigating neratinib safety and efficacy when givenwith paclitaxel (Taxol(R), Bristol-Myers Squibb) in patients withHER-2 dependent solid tumors. The data gathered from both trials arescheduled to be presented at the 45th Annual Meeting of the AmericanSociety of Clinical Oncology Annual Meeting in Orlando, Florida, fromMay 29 to June 2, 2009. Neratinib is an investigational orallyadministered irreversible inhibitor of the HER-2 and EGFR kinases.
"The data gathered from these studies provide additional evidencesuggesting that neratinib, when combined with these therapies, is anactive agent in HER-2 positive breast cancer," says Ramona Swaby,M.D., Department of Medical Oncology, Fox Chase Cancer Center,Philadelphia, PA. "While improvements have been made in treatingHER-2 positive breast cancer, there remains an unmet medical need formore therapies for patients with metastatic breast cancer. These datawarrant ongoing and future investigations to further understand andevaluate the utility of neratinib against this aggressive disease."
Neratinib (HKI-272) in Combination with Trastuzumab for theTreatment of Advanced Breast Cancer
This ongoing phase 1/2 study of neratinib in combination withtrastuzumab evaluated patients with advanced ErbB-2 positive breastcancer that progressed following therapy with trastuzumab, thestandard of care in this disease setting. The primary endpoint of thetwo-part study is 16-week progression-free survival (PFS). The firstpart of the study includes patients being administered neratinib (160mg or 240 mg) daily plus weekly trastuzumab (4 mg/kg IV loading dosethen 2 mg/kg). In the second part of the study, patients receive aweekly dose of trastuzumab with daily neratinib (240 mg).
To date, 45 patients have been enrolled and 28 patients wereevaluable for efficacy. The 16-week PFS rate (for part 2) was 45percent (95 percent CI, 26 percent to 62 percent); median PFS was 16weeks (95 percent CI, 15 to 31 weeks). The complete response rate was7 percent, while 21 percent of evaluable patients showed partialresponse. The objective response rate was 29 percent (95 percent CI,13 percent to 49 percent).
In this study, adverse events of any grade were diarrhea, nausea,anorexia, vomiting, asthenia, rash and fatigue. In the 45 patientsenrolled in this study, diarrhea was the most common adverse event,observed in 91 percent of patients, and was the most significantgrade 3 or 4 adverse event, occurring in 16 percent of patients. Twopatients receiving neratinib 240 mg reported adverse events leadingto discontinuation of therapy.
Safety and Efficacy of Neratinib (HKI-272) in Combination withPaclitaxel in Patients with Solid Tumors
In a separate phase 1/2, open-label, 2-part study, ascendingmultiple daily oral doses of neratinib (160 mg, 240 mg) wereadministered in combination with IV paclitaxel 80 mg/m2, iftolerable, or 70 mg/m2 on days 1, 8 and 15. Patients with solidtumors (endometrial, cervical, colorectal and esophageal cancers)were entered in the phase 1 portion (part 1), and only patients withmetastatic ErbB-2 positive breast cancer were enrolled in part 2.Safety and efficacy were investigated in patients with ErbB-2positive metastatic breast cancer.
A total of 102 patients were enrolled in part 2 of the study and97 patients were evaluable for efficacy. The overall response rate at16-weeks (for part 2) was 63 percent (80 percent CI, 55.9 percent to69.4).
In this preliminary analysis, the adverse event profile of thecombination of neratinib (240 mg) plus paclitaxel (80 mg/m2) wassimilar to that reported with both agents as monotherapy. Adverseevents of any grade were diarrhea, alopecia, infection, peripheralneuropathy, leucopenia, anemia, nausea, rash, fatigue and vomiting.The most common adverse event was diarrhea, observed in 89 percent ofthe 102 patients enrolled in part 2 and was the most significantgrade 3 or 4 adverse event, occurring in 25 percent of patients.Fourteen patients had dose reductions and one patient withdrew fromthe study due to an adverse event.
"Emerging clinical data continue to suggest that neratinib, incombination with these therapies is tolerable and active in treatingHER-2 positive disease, even in those women who have progressed whileon other targeted therapies," says Gary L. Stiles, M.D., ChiefMedical Officer, Wyeth Pharmaceuticals. "These additional data buildupon results presented at the 2008 San Antonio Breast CancerSymposium, and Wyeth is committed to evaluating further the potentialof this investigational therapy."
In 2008, the American Cancer Society estimated that more than182,000 women in the United States would be diagnosed with breastcancer, and more than 40,000 would die from the disease. The HER-2receptor is over-expressed in 25 percent to 30 percent of patientswith breast cancer.
Wyeth is one of the world's largest research-drivenpharmaceutical and health care products companies. It is a leader inthe discovery, development, manufacturing and marketing ofpharmaceuticals, vaccines, biotechnology products, nutritionals andnon-prescription medicines that improve the quality of life forpeople worldwide. The Company's major divisions include WyethPharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge AnimalHealth.
The statements in this press release that are not historicalfacts are forward-looking statements that are subject to risks anduncertainties that could cause actual results to differ materiallyfrom those expressed or implied by such statements. In particular,clinical trial data are subject to differing interpretations, and theviews of regulatory agencies, medical and scientific experts andothers may differ from ours. There can be no assurance that neratinibwill ever receive regulatory approval or be successfully developedand commercialized. Other risks and uncertainties that could causeactual results to differ materially from those expressed or impliedby forward-looking statements include, among others, risks related toour proposed merger with Pfizer, including satisfaction of theconditions of the proposed merger on the proposed timeframe or atall, contractual restrictions on the conduct of our business includedin the merger agreement, and the potential for loss of key personnel,disruption in key business activities or any impact on ourrelationships with third parties as a result of the announcement ofthe proposed merger; the inherent uncertainty of the timing andsuccess of, and expense associated with, research, development,regulatory approval and commercialization of our products andpipeline products; government cost-containment initiatives;restrictions on third-party payments for our products; substantialcompetition in our industry, including from branded and genericproducts; emerging data on our products and pipeline products; theimportance of strong performance from our principal products and ouranticipated new product introductions; the highly regulated nature ofour business; product liability, intellectual property and otherlitigation risks and environmental liabilities; the outcome ofgovernment investigations; uncertainty regarding our intellectualproperty rights and those of others; difficulties associated with,and regulatory compliance with respect to, manufacturing of ourproducts; risks associated with our strategic relationships; globaleconomic conditions; interest and currency exchange rate fluctuationsand volatility in the credit and financial markets; changes ingenerally accepted accounting principles; trade buying patterns; theimpact of legislation and regulatory compliance; risks anduncertainties associated with global operations and sales; and otherrisks and uncertainties, including those detailed from time to timein our periodic reports filed with the Securities and ExchangeCommission, including our current reports on Form 8-K, quarterlyreports on Form 10-Q and annual report on Form 10-K, particularly thediscussion under the caption "Item 1A, Risk Factors" in our AnnualReport on Form 10-K for the year ended December 31, 2008, which wasfiled with the Securities and Exchange Commission on February 27,2009. The forward-looking statements in this press release arequalified by these risk factors. We assume no obligation to publiclyupdate any forward-looking statements, whether as a result of newinformation, future developments or otherwise.
ots Originaltext: Wyeth PharmaceuticalsIm Internet recherchierbar: http://www.presseportal.de
Contact:Danielle Halstrom, +1-215-280-3898 (on site), of Wyeth Pharmaceuticals, or Douglas Petkus, +1-973-660-5218; or Investors, Justin Victoria, +1-973-660-5340, both of Wyeth