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AstraZeneca and Merck Rapidly Advance LYNPARZA® (olaparib) in Japan With a Second Regulatory SubmissionAstraZeneca and Merck (NYSE:MRK), known as MSD outside the U.S. and Canada, today announced that they have submitted a new drug application (NDA) to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) for the use of LYNPARZA® (olaparib) tablets in unresectable or recurrent BRCA-mutated breast cancer, with a decision expected in the second half of 2018. The Japan NDA is based on the positive results from the Phase III OlympiAD trial published in the New England Journal of Medicine. This is the second NDA for LYNPARZA in Japan where the medicine is currently under review for use in ovarian cancer, with a PMDA decision for this indication anticipated in the first half of 2018. LYNPARZA tablets are currently being tested in a range of tumor types in addition to ovarian and breast, including prostate and pancreatic cancers. IMPORTANT SAFETY INFORMATION
DOSING AND ADMINISTRATION To avoid substitution errors and overdose, do not substitute LYNPARZA (olaparib) tablets with LYNPARZA capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Recommended tablet dose is 300 mg, taken orally twice daily, with or without food. Continue treatment until disease progression or unacceptable toxicity. For adverse reactions, consider dose interruption or dose reduction. WARNINGS AND PRECAUTIONS There are no contraindications for LYNPARZA. Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some of these patients also had a history of previous cancer or bone marrow dysplasia. Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (=Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed. Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt treatment with LYNPARZA and initiate prompt investigation. Discontinue LYNPARZA (olaparib) if pneumonitis is confirmed and treat patient appropriately. Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving the final dose. ADVERSE REACTIONS-Maintenance Setting Most common adverse reactions (Grades 1-4) in =20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%). Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), and decreased appetite (21%). Most common laboratory abnormalities (Grades 1-4) in =25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%). ADVERSE REACTIONS-Advanced gBRCAm ovarian cancer Most common adverse reactions (Grades 1-4) in =20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%). Most common laboratory abnormalities (Grades 1-4) in =25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: decrease in hemoglobin (90%), increase in mean corpuscular volume (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%). DRUG INTERACTIONS Anticancer Agents: Clinical studies of LYNPARZA (olaparib) in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation ad prolongation of myelosuppressive toxicity. CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment. CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, be aware of a potential for decreased efficacy of LYNPARZA. USE IN SPECIFIC POPULATIONS Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients. Lactation: No data are available regarding the presence of olaparib in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose. Hepatic Impairment: No adjustment to the starting dose is required in patients with mild hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment. Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr 51-80 mL/min). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr =30 mL/min). Please see complete Prescribing Information, including Patient Information (Medication Guide)
About OlympiAD
About LYNPARZA® (olaparib) LYNPARZA is the foundation of AstraZeneca's industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.
About Metastatic Breast Cancer
About Germline BRCA Mutations
About the AstraZeneca and Merck Strategic Oncology Collaboration
Merck's Focus on Cancer As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's 2016 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC (News - Alert)) available at the SEC's Internet site (www.sec.gov). View source version on businesswire.com: http://www.businesswire.com/news/home/20171023005473/en/ |