Supplemental New Drug Application being reviewed under FDA Real-Time Oncology Review (RTOR) and Project ORBIS pilot programs
NEW YORK, NY, USA I December 28, 2020 I Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for LORBRENA ® (lorlatinib) as a first-line treatment for people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). The sNDA is based on data from the pivotal CROWN study and is being reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in April 2021.
LORBRENA is a third-generation ALK inhibitor specifically developed to inhibit the most common tumor mutations that drive resistance to current medications and to address brain metastases. Up to 40% of people with ALK-positive lung cancer present with brain metastases.1,2,3
“The decision by the FDA to evaluate our application for LORBRENA under its innovative review pathways, which aim to speed up availability of potentially life-changing medicines, underscores the significance of the CROWN data and potential impact of LORBRENA as an initial therapy for people with ALK-positive advanced non-small cell lung cancer,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “We look forward to working with the FDA to bring this treatment option to patients as quickly as possible.”
The RTOR program is intended to create a more efficient review process to bring safe and effective treatments to people as early as possible. The program allows the FDA to review clinical trial data from certain applications before the complete application is formally submitted. Review under the program does not guarantee or influence the approvability of the application.4
The FDA also will conduct the review under Project ORBIS, an initiative introduced in 2019, which provides a framework for potential concurrent submissions and collaborative review with health authorities in Canada, Singapore, Switzerland, Australia, Brazil and the United Kingdom. Under Project ORBIS, collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries.5
The submission is supported by positive results from the Phase 3 CROWN trial, which met the primary endpoint of improved progression-free survival (PFS) versus XALKORI® (crizotinib) in people with previously untreated advanced ALK-positive NSCLC. Detailed results were published in the New England Journal of Medicine and previously presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
In 2018, the FDA approved LORBRENA for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. This indication was approved under accelerated approval based on tumor response rate and duration of response. Data from the CROWN study will also support the conversion to a full approval for the use of LORBRENA for this indication.
About the CROWN Study
CROWN is a Phase 3, randomized, open-label, parallel 2-arm trial in which 296 people with previously untreated advanced ALK-positive NSCLC were randomized 1:1 to receive LORBRENA monotherapy (n=149) or XALKORI monotherapy (n=147). The primary endpoint of the CROWN trial is progression-free survival (PFS) based on blinded independent central review (BICR). Secondary endpoints include PFS based on investigator’s assessment, overall survival (OS), objective response rate (ORR), intracranial objective response, and safety.
About Non-Small Cell Lung Cancer
Lung cancer is the number one cause of cancer-related death around the world.5 NSCLC accounts for approximately 80-85% of lung cancers,6 with ALK-positive tumors occurring in about 3-5% of NSCLC cases.7 In 2020, an estimated 13,000 new cases of ALK-positive NSCLC will be diagnosed in the G7.8
About LORBRENA® (lorlatinib)
LORBRENA is a tyrosine kinase inhibitor (TKI) that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORBRENA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. LORBRENA is approved in the U.S. for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on:
- crizotinib and at least one other ALK inhibitor for metastatic disease; or
- alectinib as the first ALK inhibitor therapy for metastatic disease; or
- ceritinib as the first ALK inhibitor therapy for metastatic disease.
- This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The full prescribing information for LORBRENA can be found here.
About XALKORI® (crizotinib)
XALKORI is a TKI indicated for the treatment of patients with metastatic NSCLC whose tumors are ALK- or ROS1-positive as detected by an FDA-approved test. 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 60 countries.
The full prescribing information for XALKORI can be found here.
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 23 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.
Pfizer Inc.: 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 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.
1 Peters S. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer. N Engl J Med. 2017;377:829-38.
2 Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALKrearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389:917–929
3 Gainor JF, Tseng D, Yoda S, et al. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non-small-cell lung cancer. JCO Precis Oncol. 2017;2017.
4 US Food and Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program. Accessed October 2020.
5 U.S. Food and Drug Administration. Project Orbis. https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis. Accessed November 2020.
6 World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2018: Lung fact sheet. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed November 2020.
7 American Cancer Society. What is lung cancer? https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed November 2020.
8 Garber K. ALK, lung cancer, and personalized therapy: portent of the future? J Natl Cancer Inst. 2010;102:672-675.
9 Decision Resource Group, Kantar Health.
SOURCE: Pfizer
Post Views: 25
Supplemental New Drug Application being reviewed under FDA Real-Time Oncology Review (RTOR) and Project ORBIS pilot programs
NEW YORK, NY, USA I December 28, 2020 I Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for LORBRENA ® (lorlatinib) as a first-line treatment for people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). The sNDA is based on data from the pivotal CROWN study and is being reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in April 2021.
LORBRENA is a third-generation ALK inhibitor specifically developed to inhibit the most common tumor mutations that drive resistance to current medications and to address brain metastases. Up to 40% of people with ALK-positive lung cancer present with brain metastases.1,2,3
“The decision by the FDA to evaluate our application for LORBRENA under its innovative review pathways, which aim to speed up availability of potentially life-changing medicines, underscores the significance of the CROWN data and potential impact of LORBRENA as an initial therapy for people with ALK-positive advanced non-small cell lung cancer,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “We look forward to working with the FDA to bring this treatment option to patients as quickly as possible.”
The RTOR program is intended to create a more efficient review process to bring safe and effective treatments to people as early as possible. The program allows the FDA to review clinical trial data from certain applications before the complete application is formally submitted. Review under the program does not guarantee or influence the approvability of the application.4
The FDA also will conduct the review under Project ORBIS, an initiative introduced in 2019, which provides a framework for potential concurrent submissions and collaborative review with health authorities in Canada, Singapore, Switzerland, Australia, Brazil and the United Kingdom. Under Project ORBIS, collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries.5
The submission is supported by positive results from the Phase 3 CROWN trial, which met the primary endpoint of improved progression-free survival (PFS) versus XALKORI® (crizotinib) in people with previously untreated advanced ALK-positive NSCLC. Detailed results were published in the New England Journal of Medicine and previously presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
In 2018, the FDA approved LORBRENA for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. This indication was approved under accelerated approval based on tumor response rate and duration of response. Data from the CROWN study will also support the conversion to a full approval for the use of LORBRENA for this indication.
About the CROWN Study
CROWN is a Phase 3, randomized, open-label, parallel 2-arm trial in which 296 people with previously untreated advanced ALK-positive NSCLC were randomized 1:1 to receive LORBRENA monotherapy (n=149) or XALKORI monotherapy (n=147). The primary endpoint of the CROWN trial is progression-free survival (PFS) based on blinded independent central review (BICR). Secondary endpoints include PFS based on investigator’s assessment, overall survival (OS), objective response rate (ORR), intracranial objective response, and safety.
About Non-Small Cell Lung Cancer
Lung cancer is the number one cause of cancer-related death around the world.5 NSCLC accounts for approximately 80-85% of lung cancers,6 with ALK-positive tumors occurring in about 3-5% of NSCLC cases.7 In 2020, an estimated 13,000 new cases of ALK-positive NSCLC will be diagnosed in the G7.8
About LORBRENA® (lorlatinib)
LORBRENA is a tyrosine kinase inhibitor (TKI) that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORBRENA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. LORBRENA is approved in the U.S. for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on:
- crizotinib and at least one other ALK inhibitor for metastatic disease; or
- alectinib as the first ALK inhibitor therapy for metastatic disease; or
- ceritinib as the first ALK inhibitor therapy for metastatic disease.
- This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The full prescribing information for LORBRENA can be found here.
About XALKORI® (crizotinib)
XALKORI is a TKI indicated for the treatment of patients with metastatic NSCLC whose tumors are ALK- or ROS1-positive as detected by an FDA-approved test. 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 60 countries.
The full prescribing information for XALKORI can be found here.
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 23 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.
Pfizer Inc.: 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 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.
1 Peters S. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer. N Engl J Med. 2017;377:829-38.
2 Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALKrearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389:917–929
3 Gainor JF, Tseng D, Yoda S, et al. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non-small-cell lung cancer. JCO Precis Oncol. 2017;2017.
4 US Food and Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program. Accessed October 2020.
5 U.S. Food and Drug Administration. Project Orbis. https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis. Accessed November 2020.
6 World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2018: Lung fact sheet. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed November 2020.
7 American Cancer Society. What is lung cancer? https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed November 2020.
8 Garber K. ALK, lung cancer, and personalized therapy: portent of the future? J Natl Cancer Inst. 2010;102:672-675.
9 Decision Resource Group, Kantar Health.
SOURCE: Pfizer
Post Views: 25
