Pfizer Prepares for Voluntary Withdrawal of U.S. New Drug Application and for Discontinuation of Commercial Availability of Mylotarg®

NEW YORK, June 21 /PRNewswire-FirstCall/ -- Pfizer Inc. (NYSE: PFE) announced today that based on discussions with the U.S. Food and Drug Administration (FDA), it will be discontinuing commercial availability of Mylotarg® (gemtuzumab ozogamicin for Injection) (used for the treatment of relapsed acute myeloid leukemia (AML)) in the United States and that it will be voluntarily withdrawing the new drug application (NDA) for Mylotarg effective October 15, 2010.

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The approval of single agent Mylotarg in the U.S. was granted under FDA's accelerated approval regulations based on overall response rate in three non-comparative studies and required submission of additional data to confirm clinical benefit.  The required post-approval study (SWOG S0106) combining chemotherapy and Mylotarg did not demonstrate improved survival compared with chemotherapy alone in patients with previously untreated AML.

Additionally, among all patients evaluable for early toxicity the fatal induction toxicity rate was significantly higher in subjects given the combination of standard induction chemotherapy and Mylotarg than in those treated with chemotherapy alone.  After extensive discussions with the FDA, Pfizer has decided to withdraw the NDA effective October 15, 2010.

"We are disappointed that the study did not confirm the clinical benefit of Mylotarg.  Our primary concern is for patients who suffer from AML, which remains a very serious and difficult-to-treat disease with limited treatment options.  We advise patients to contact their physicians for further information," said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer Oncology Business Unit.

Patients who are currently taking Mylotarg and those patients who have been prescribed Mylotarg may continue their course of therapy, in consultation with their physicians.  However, Pfizer recommends that no new patients in the U.S. be prescribed Mylotarg.  Future use of Mylotarg for new patients in the U.S. will require physician submission of an Investigational New Drug (IND) application to the FDA.  

The Company is also working with Health Authorities outside the U.S. and will keep patients, regulatory authorities, investigators and clinicians informed about FDA actions and appropriate next steps for Mylotarg.

For further information please contact Pfizer Medical Information at 1-800-438-1985 or at www.pfizer.com.

Mylotarg® (gemtuzumab ozogamicin for Injection) was approved in the U.S. as a single agent for patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.  Patients treated with Mylotarg receive one course of treatment that consists of two doses typically given 14 days apart.

AML is a relatively uncommon disease that affects approximately 13,000 new patients annually in the U.S.  It is estimated that less than 2,500 patients receive Mylotarg annually in the U.S.

SWOG S0106 Post Approval Study

With the agreement of FDA, a Phase 3 randomized, comparative controlled trial (SWOG S0106) using Mylotarg in combination with other chemotherapeutic agents (daunorubicin and cytosine arabinoside) versus chemotherapy alone in first-line AML patients under the age of 61 was conducted to confirm clinical benefit for Mylotarg.  A total of 627 patients were enrolled in this study.  Although SWOG S0106 did not confirm the clinical benefit, the results do not directly impact the risk/benefit profile of Mylotarg in its approved indication as a single agent.

Additionally, among all patients evaluable for early toxicity, the fatal induction toxicity rate was significantly higher in the daunorubicin and cytosine arabinoside + Mylotarg arm compared to the daunorubicin and cytosine arabinoside arm (16/283=5.7% vs. 4/281=1.4%, P=0.01).

About Mylotarg® (gemtuzumab ozogamicin for Injection)

Important safety information:

Mylotarg should be administered under the supervision of physicians experienced in the treatment of acute leukemia and in facilities equipped to monitor and treat leukemia patients.

There are no controlled trials demonstrating efficacy and safety using Mylotarg in combination with other chemotherapeutic agents. Therefore, Mylotarg should only be used as a single agent chemotherapy and not in combination chemotherapy regimens outside clinical trials.  Severe myelosuppression occurs when Mylotarg is used at recommended doses.

Mylotarg administration can result in severe hypersensitivity reactions (including anaphylaxis), and other infusion-related reactions which may include severe pulmonary events. Infrequently, hypersensitivity reactions and pulmonary events have been fatal.  In most cases, infusion-related symptoms occurred during the infusion or within 24 hours of administration of Mylotarg and resolved.

Mylotarg infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension.  Patients should be monitored until signs and symptoms completely resolve. Discontinuation of Mylotarg (gemtuzumab ozogamicin for Injection) treatment should be strongly considered for patients who develop anaphylaxis, pulmonary edema, or acute respiratory distress syndrome.  Since patients with high peripheral blast counts may be at greater risk for pulmonary events and tumor lysis syndrome, physicians should consider leukoreduction with hydroxyurea or leukapheresis to reduce the peripheral white count to below 30,000 per microliter prior to administration of Mylotarg.

Hepatotoxicity, including severe hepatic veno-occlusive disease (VOD), has been reported in association with the use of Mylotarg as a single agent, as part of a combination chemotherapy regimen, and in patients without a history of liver disease or hematopoietic stem-cell transplant (HSCT).  (See WARNINGS and ADVERSE REACTIONS sections of the full Information.) Patients who receive Mylotarg either before or after HSCT, patients with underlying hepatic disease or abnormal liver function, and patients receiving Mylotarg in combinations with other chemotherapy may be at increased risk for developing severe VOD.

Death from liver failure and from VOD has been reported in patients who receive Mylotarg (gemtuzumab ozogamicin for Injection).  Physicians should monitor their patients carefully for symptoms of hepatotoxicity, particularly VOD.  These symptoms can include: rapid weight gain, right upper quadrant pain, hepatomegaly, ascites, elevations in bilirubin and/or liver enzymes.  However, careful monitoring may not identify all patients at risk or prevent the complications of hepatotoxicity.

Mylotarg may cause fetal harm when administered to a pregnant woman.  The reported rates of Grades 3 and 4 thrombocytopenia, neutropenia, anemia, and bleeding were 99%, 98%, 47%, and 15%, respectively. Twenty-eight percent of patients experienced severe infections, including sepsis (16%) and pneumonia (7%). The most common adverse events were fever (85%), chills (73%), nausea (70%), vomiting (63%), asthenia (44%), diarrhea (38%), abdominal pain (37%), headache (35%), stomatitis (32%), dyspnea (32%), epistaxis (31%), hypokalemia (31%), anorexia (29%), sepsis (25%), constipation (25%), local reaction (25%), nonspecific rash (22%), herpes simplex (22%), and neutropenic fever (21%).

Mylotarg can produce a postinfusion symptom complex of fever and chills and less commonly hypotension and dyspnea during the first 24 hours after administration.  Patients should receive diphenhydramine 50 mg po and acetaminophen 650-1000 mg po one hour before Mylotarg (gemtuzumab ozogamicin for Injection) administration.  Two additional doses of acetaminophen 650-1000 mg po every four hours may be given.  Vital signs should be monitored during infusion and for four hours following infusion.  

Please see full prescribing information at: http://www.wyeth.com/content/showlabeling.asp?id=119.

About Pfizer Oncology

Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide.  Our strong pipeline, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers, including breast, lung, prostate, sarcoma, melanoma, and various hematologic cancers.  Pfizer Oncology has biologics and small molecules in clinical development and more than 200 clinical trials underway.

By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time. For more information please visit www.Pfizer.com.

SOURCE Pfizer Inc.