Pfizer Receives Positive CHMP Opinion for DAURISMO®(glasdegib)for Certain Adult Patients with Newly Diagnosed or Secondary Acute Myeloid Leukemia (AML)
NEW YORK, May 1 – Pfizer Inc. (NYSE: PFE) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for DAURISMO®(glasdegib), a Hedgehog pathway inhibitor, in combination with low-dose cytarabine (LDAC), a type of chemotherapy, for the treatment of newly diagnosed (denovo or secondary) acute myeloid leukemia in adult patients who are not candidates for standard chemotherapy. The CHMP’s opinion will now be reviewed by the European Commission, with a decision expected in the coming months.
“Acute myeloid leukemia is a life-threatening disease with poor survival rates, especially for those whom standard intensive chemotherapy is not an option,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Pfizer Oncology. “People living with this type of acute myeloid leukemia in Europe are in dire need of new treatment options, and with the CHMP positive opinion for DAURISMO, we are one step closer to being able to offer a new treatment option that may prolong survival.”
The Marketing Authorization Application was based on results from the Phase 2 BRIGHT 1003 trial, which showed DAURISMO nearly doubled median overall survival compared to LDAC alone (8.3 months vs. 4.3 months, HR
0.463, 95% CI [0.299,0.717]) in patients with previously untreated (de novo or secondary) AML were not eligible for intensive chemotherapy.1
The positive CHMP opinion of DAURISMO follows the medicine’s approval by the U.S. Food and Drug Administration (FDA) in November 2018.1 In the U.S., DAURISMO is approved in combination with LDAC, for the treatment of newly diagnosed AML in adult patients who are 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy.1
DAURISMO is not approved for any indication in any market outside the U.S. and Canada.
The full U.S. Prescribing Information, including BOXED WARNING, for DAURISMO can be found here.
IMPORTANT DAURISMO SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
WARNING:EMBRYO-FETALTOXICITY: DAURISMO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman.
DAURISMO is embryotoxic, fetotoxic, and teratogenic in animals. Conduct pregnancy testing in females of reproductive potential prior to initiation of DAURISMO treatment. Advise females of reproductive potential to use effective contraception during treatment with DAURISMO and for at least 30 days after the last dose. Advise males of the potential risk of DAURISMO exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with DAURISMO and for at least 30 days after the last dose to avoid potential drug exposure.
Blood Donation: Advise patients not to donate blood or blood products while taking DAURISMO and for at least 30 days after the last dose, because their blood or blood products might be given to a female of reproductive potential.
QTc Interval Prolongation: Patients treated with DAURISMO can develop QTc prolongation and ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia. Of the 98 evaluable patients treated with DAURISMO 100 mg in combination with low-dose cytarabine in the clinical trial, 5% were found to have a QTc interval greater than 500 ms and 4% of patients had an increase from baseline QTc greater than 60 ms. The clinical trial excluded patients with baseline QTc of greater than 470 ms or with a history of long QT syndrome or uncontrolled cardiovascular disease. Monitor electrocardiograms (ECGs) and electrolytes. Concomitant use of DAURISMO with drugs known to prolong the QTc interval and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. In patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring is recommended. Interrupt DAURISMO if QTc interval is >500 ms and discontinue permanently for patients who develop QTc interval prolongation with signs or symptoms of life- threatening arrhythmia.
AdverseReactions: Most common adverse reactions associated with DAURISMO (incidence ≥20%) were anemia (43%), fatigue (36%), hemorrhage (36%), febrile neutropenia (31%), musculoskeletal pain (30%), edema (30%), thrombocytopenia (30%), nausea (29%), dyspnea (23%), decreased appetite (21%), dysgeusia (21%), mucositis (21%), constipation (20%), and rash (20%).
Drug Interactions: Co-administration with strong CYP3A4 inhibitors increased DAURISMO plasma concentrations, which may increase the risk of adverse reactions including QTc interval prolongation. Consider alternative therapies that are not strong CYP3A4 inhibitors during treatment with DAURISMO and monitor patients for increased risk of adverse reactions including QTc interval prolongation. Strong and moderate CYP3A4 inducers should be avoided due to decreased DAURISMO plasma concentrations, which may reduce efficacy. If concomitant use of moderate CYP3A4 inducers cannot be avoided, increase the DAURISMO dosage to 200 mg once daily (if the patient is taking 100 mg) and 100 mg once daily (if the patient is taking 50 mg) as tolerated. Co- administration of DAURISMO with QTc-prolonging drugs may increase the risk of QTc interval prolongation. Avoid co-administration of QTc- prolonging drugs with DAURISMO or replace with alternative therapies. If co-administration of a QTc-prolonging drug is unavoidable, monitor patients for increased risk of QTc interval prolongation.
Lactation: Because of the potential for serious adverse reactions from DAURISMO in a breastfed child, advise women who are taking DAURISMO not to breastfeed or provide breast milk to infants or children during treatment and for at least 30 days after the last dose.
Renal Impairment: No dosage modification is recommended for patients with mild to severe renal impairment. Monitor patients with severe renal impairment (eGFR 15 to 29 mL/min) for increased risk of adverse reactions, including QTc interval prolongation, due to increased glasdegib concentrations.
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of patients. Today, Pfizer Oncology has an industry-leading portfolio of 22 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, prostate, kidney and lung cancers, as well as leukemia and melanoma.
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At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE:The information contained in this release is as of May 1, 2020. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
Thisreleasecontainsforward-lookinginformationabout DAURISMO (glasdegib), including a potential indication in the EU and DAURISMO’s potential benefits, that involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of DAURISMO; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when applications for DAURISMO may be filed in any other jurisdictions; whether and when the European Commission may
approve the pending application for DAURISMO in the EU and whether and when any such other applications for DAURISMO that may be pending or filed may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether DAURISMO will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of DAURISMO; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2019 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the
1 DAURISMOTM (glasdegib) Prescribing Information. New York. NY: Pfizer Inc: 2020.