NEW YORK–(BUSINESS WIRE) January 14, 2021 — Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) for Xalkori® (crizotinib) for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive. The safety and efficacy of Xalkori have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL. ALCL is a rare form of non-Hodgkin lymphoma (NHL) and accounts for approximately 30% of cases of NHL in young people.1,2,3 Approximately 90% of ALCL cases in young people are ALK-positive.4,5,6
“We are proud to deliver the first biomarker-driven therapy for children and young adults with ALCL. Xalkori offers a meaningful new treatment option for young patients with relapsed or refractory ALK-positive ALCL,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “Xalkori transformed the treatment of ALK-positive non-small cell lung cancer as the first biomarker-driven therapy for that disease, and this approval is a notable milestone in our journey to continue to follow the science to address cancers with significant unmet need.”
Although the majority of people with ALK-positive ALCL respond well to chemotherapy and experience long-term remission, a number of patients will unfortunately relapse or require alternative treatment approaches.7
“With increased attention being placed on the development of targeted agents and the importance of ALK in pediatric patients with ALCL, the approval of Xalkori is a significant victory in our ongoing fight against these cancers that provides an outpatient oral medication with the real possibility of robust and sustained responses,” said Yael Mossé, M.D., Associate Professor of Pediatrics at the University of Pennsylvania/ Children’s Hospital of Philadelphia and Principal Investigator for the pivotal study run through the Children’s Oncology Group. “ALK fusions play an important role in the pathology of ALCL, and it’s exciting that Xalkori is able to leverage this dependence to provide a treatment option for young people faced with ALCL disease progression.”
The FDA approval is based on results from Study ADVL0912 (NCT00939770), a multicenter, single arm, open-label study in 121 patients between the ages of 1 and 21 that included 26 patients with relapsed or refractory, systemic ALK-positive ALCL after at least one systemic treatment. Treatment with Xalkori resulted in an objective response rate of 88%. Among the 23 patients who achieved a response, 39% maintained their response for at least 6 months and 22% maintained their response for at least 12 months.8
The safety profile of Xalkori in ALK-positive ALCL in children and young adults is generally consistent with that observed in patients with ALK-positive and ROS1-positive metastatic NSCLC. The most common adverse reactions (≥35%), excluding laboratory abnormalities, were diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough and pruritis. The most common Grade 3 or 4 laboratory abnormalities (≥15%) included neutropenia, lymphopenia and thrombocytopenia. Grade 4 laboratory abnormalities (≥15%) included neutropenia (62%), lymphopenia (35%) and thrombocytopenia (19%). In Study ADVL0912, visual disorders occurred in 46% of 121 patients treated with Xalkori, including 65% of the 26 patients diagnosed with ALCL.8
“Crizotinib represents an exciting new development in the treatment of this disease,” said Meghan Gutierrez, Chief Executive Officer at the Lymphoma Research Foundation. “Researchers have made significant progress in our understanding of ALCL, which we hope will continue to improve treatment strategies and the options for children with ALCL. Today’s news builds upon this progress and provides hope to pediatric patients with ALCL and their loved ones.”
Xalkori received Breakthrough Therapy designation (BTD) from the FDA for the ALK-positive ALCL indication in May 2018. The European Medicines Agency (EMA) has agreed to a Paediatric Investigational Plan (PIP) for Xalkori including the treatment of pediatric patients with relapsed or refractory systemic ALK-positive ALCL. This agreement provides a path for a potential regulatory submission for Xalkori in pediatric patients with relapsed or refractory ALK-positive ALCL in the European Union.
About Xalkori (crizotinib)
Xalkori is a tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with metastatic NSCLC whose tumors are ALK- or ROS1-positive as detected by an FDA-approved test. In addition to the United States, Xalkori has received approval for patients with ALK-positive NSCLC in more than 90 countries including Australia, Canada, China, Japan, South Korea and the European Union. Xalkori is also approved for ROS1-positive NSCLC in more than 70 countries.
Xalkori is indicated for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. The safety and efficacy of Xalkori have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.
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 people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.
About Pfizer: Breakthroughs That Change Patients’ Lives
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 170 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 January 14, 2021. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about Xalkori® (crizotinib) and a new indication in the U.S. for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive, including their potential benefits, that involves 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 Xalkori; 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 any drug applications may be filed in any additional jurisdictions for Xalkori for the new indication (including in the European Union) or in any jurisdictions for any other potential indications for Xalkori; whether and when any such other applications may be approved by regulatory authorities, which will depend on a 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 such product candidate 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 Xalkori; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; 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 U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
1 Ward E, DeSantis C, Robbins A, et al. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 2014;64(2):83-103.
2 Drexler HG, Gignac SM, von Wasielewski R, et al. Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. Leukemia 2000;14:1533–59.
3 Medscape. Anaplastic Large Cell Lymphoma. Available at: https://emedicine.medscape.com/article/208050-overview#a4. Accessed October 2020
4 Burkhardt B, Zimmermann M, Oschlies I, et al. The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. Br J Haematol 2005;131(1):39-49.
5 Le Deley MC, Rosolen A, Williams DM, et al. Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: Results of the randomized ALCL99 vinblastine trial. J Clin Oncol 2010;28(25):3987–93.
6 Mussolin L, Pillon M, Bonato P, et al. Cytogenetic analysis of pediatric anaplastic large cell lymphoma. Pediatr Blood Cancer 2010;55(3):446-51.
7 P. Mossé, Yael, D. Voss, Stephan, S. Lim, Megan, et al. 2017. Journal of Clinical Oncology. Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children’s Oncology Group Study. 35. JCO.2017.73.483. 10.1200/JCO.2017.73.4830.
8 XALKORI® (crizotinib) Prescribing Information. New York. NY: Pfizer Inc: 2021.
Source: Pfizer Inc.
Posted: January 2021
Xalkori (crizotinib) FDA Approval History