FDA approves Mylotarg for treatment of acute myeloid leukemia

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Pfizer Inc. announced that the U.S. Food and Drug Administration approved MYLOTARG™ (gemtuzumab ozogamicin) for adults with newly diagnosed CD33-positive acute myeloid leukemia (AML),

and adults and children 2 years and older with relapsed or refractory CD33-positive AML.1 MYLOTARG is the first therapy with an indication that includes pediatric AML. It is also the only AML therapy that targets CD33, an antigen expressed on AML cells in up to 90% of patients.

“The FDA approval of MYLOTARG fills a critical unmet need for many adults and children with AML, which can be fatal in a matter of months or even weeks if not treated and has a high relapse rate,” said Liz Barrett, global president, Pfizer Oncology. “Based on clinical data, real-world experience and support from the AML community, we are grateful MYLOTARG now has the potential to help a broad range of AML patients.”

MYLOTARG was originally approved in 2000 at a higher dose under the FDA’s accelerated approval program for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years or older and who were not considered candidates for other cytotoxic chemotherapy. In 2010, Pfizer voluntarily withdrew MYLOTARG in the U.S. after a confirmatory trial failed to show clinical benefit and there was a higher rate of fatal toxicity compared to chemotherapy. MYLOTARG has remained on the market in Japan and has been available to individual patients through Pfizer’s compassionate use programs. Due to the critical unmet need for patients with AML, there remained great interest among AML clinicians to evaluate MYLOTARG using different doses and different schedules. These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of MYLOTARG.

“Today is an important day for patients, their families and the entire AML community, as the approval of MYLOTARG brings forth a long-awaited treatment option that may lead to deeper, more durable remissions for patients with AML,” said Jorge Cortes, MD, University of Texas, MD Anderson Cancer Center. “After many years, we are finally seeing progress in the treatment of AML, which has renewed my hope in improving outcomes for my patients. I am pleased that I can now offer many adult and pediatric patients targeted treatment with MYLOTARG.”

Today’s approval of MYLOTARG is based on several investigator-led clinical trials, including ALFA-0701, AML-19 and MyloFrance-1.1

The ALFA-0701 trial was a Phase 3, multicenter, randomized, open-label study of 271 patients with newly-diagnosed de novo AML, using a new, lower fractionated dose of MYLOTARG. Patients received MYLOTARG 3 mg/m2 on days 1, 4 and 7 in combination with conventional chemotherapy or chemotherapy alone. The primary endpoint was event-free survival (EFS). Administering MYLOTARG (n=135) in addition to standard induction chemotherapy resulted in a significant improvement in EFS compared with chemotherapy alone (n=136) in patients with newly diagnosed AML. Event-free survival was 17.3 months for patients receiving MYLOTARG compared with 9.5 months for those receiving chemotherapy alone (HR = 0.56 [95% CI: (0.42, 0.76)]).1

Study AML-19 was a multicenter, randomized, open-label Phase 3 study comparing single agent MYLOTARG (n=118) to best supportive care (n=119) for elderly patients who could not tolerate other AML therapies. As initial treatment, patients received MYLOTARG 6 mg/m2 on day 1 and MYLOTARG 3 mg/m2 on day 8. As continued treatment, patients without evidence of disease progression received MYLOTARG 2 mg/m2 on day 1 every 4 weeks. The efficacy of MYLOTARG was established on the basis of a significant improvement in overall survival (OS). Median OS was 4.9 months for patients receiving MYLOTARG compared with 3.6 months for patients receiving best supportive care (HR=0.69 [95% CI: 0.53-0.90] [2-sided p=0.005]).1

MyloFrance-1 was a Phase 2, single-arm, open-label study of 57 adult patients in first relapse. Patients received single agent MYLOTARG 3mg/m2 on days 1, 4 and 7. The efficacy of MYLOTARG was established on the basis of complete remission (CR) rate and duration of remission. In the trial, 15 (26%; 95% CI: 16%-40%) patients achieved a complete remission (CR) and median relapse-free survival (RFS) was 11.6 months.1

The U.S. labeling for MYLOTARG includes a boxed warning for hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD). Veno-occlusive disease has been reported in association with the use of MYLOTARG as a single agent and as part of a combination chemotherapy regimen (5%). In patients who received MYLOTARG, the most common (≥15%) adverse reactions were hemorrhage, infection, fever, nausea, vomiting, constipation, headache, increased ALT, increased AST, rash and mucositis.

Pfizer is committed to helping patients gain access to Pfizer medicines, including MYLOTARG, and related educational tools, resources and services, regardless of their financial or health insurance status through the company’s patient assistance programs.

About AML
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and accounts for approximately 80% of all cases of acute leukemia.2 About 21,380 people are expected to be diagnosed with AML in the United States in 2017.3 The majority of AML cases occur in adults, but about 500 children are diagnosed with AML each year.4 Acute myeloid leukemia is the second most common leukemia in children.6 The majority of children (85%) will achieve a response after initial treatment, with approximately 5% being refractory to treatment.5 Additionally, approximately 30% of children will have their disease return5. Only one in four patients with AML survive longer than five years.4

MYLOTARG is an antibody-drug conjugate (ADC) composed of the cytotoxic agent calicheamicin, attached to a monoclonal antibody (mAB) targeting CD33, an antigen expressed on the surface of myeloblasts in up to 90 percent of AML patients.6,7,8 When MYLOTARG binds to the CD33 antigen on the cell surface it is absorbed into the cell and calicheamicin is released causing cell death.1,7,8

MYLOTARG is commercially available in Japan where it is approved for the treatment of patients with relapsed or refractory CD33-positive AML who are not considered candidates for other cytotoxic chemotherapy. MYLOTARG originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development and commercialization activities for this molecule.

About Pfizer Oncology
Pfizer Oncology is committed to pursuing innovative treatments that have a meaningful impact on those living with cancer. As a leader in oncology speeding cures and accessible breakthrough medicines to patients, Pfizer Oncology is helping to redefine life with cancer. Our strong pipeline of biologics, small molecules and immunotherapies, 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. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments and licensing partners, Pfizer Oncology strives to cure or control cancer with its breakthrough medicines. Because Pfizer Oncology knows that success in oncology is not measured solely by the medicines you manufacture, but rather by the meaningful partnerships you make to have a more positive impact on people’s lives.

Pfizer Inc.: Working together for a healthier worldTM
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. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. 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.

Sally Beatty, 212-733-6566
Ryan Crowe, 212-733-8160

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