On August 17, 2017 Pfizer Inc. (NYSE:PFE) reported that the U.S. Food and Drug Administration (FDA) has approved BESPONSA (inotuzumab ozogamicin) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) (Press release, Pfizer, AUG 17, 2017, View Source [SID1234520279]).1 BESPONSA was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The approval of BESPONSA is an important step forward for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia, a rare disease that can be fatal within a matter of months if left untreated," said Liz Barrett, global president, Pfizer Oncology. "BESPONSA will help address a significant need for new treatment options in B-cell acute lymphoblastic leukemia, and may help more patients reach stem cell transplant, which provides the best chance for long term remission. We’re proud to build on our continued commitment to patients with hematologic malignancies, and will continue our work to find new treatments in acute lymphoblastic leukemia and other blood cancers."
The approval was based on results from the Phase 3 INO-VATE ALL trial, a randomized, open-label, international, multicenter study evaluating the safety and efficacy of BESPONSA compared with Investigator’s choice of chemotherapy in 326 adult patients with relapsed or refractory B-cell ALL.1
"Based on the results seen in the INO-VATE ALL trial, BESPONSA improved multiple efficacy measures, including rates of hematologic remission, MRD-negativity and stem cell transplantation," said Hagop M. Kantarjian, M. D., INO-VATE ALL lead study investigator and professor, The University of Texas MD Anderson Cancer Center. "I look forward to seeing the impact this important new therapy may have on my patients."
The complete remission rate (CR/CRi)* for patients treated with BESPONSA was 81 percent [95% CI: 72%-88%] compared to 29 percent with chemotherapy [95% CI: 21%-39%]. Among patients achieving CR/CRi, those treated with BESPONSA also demonstrated a higher rate of minimal residual disease (MRD) negativity (78% [95% CI: 68%-87%]) compared to those treated with chemotherapy (28% [95% CI: 14%-47%]). Forty-eight percent of patients treated with BESPONSA proceeded to hematopoietic stem cell transplantation (HSCT) compared to 22 percent treated with chemotherapy. The median overall survival (OS) for patients treated with BESPONSA was 7.7 months [95% CI: 6.0, 9.2] and 6.2 months [95% CI: 4.7, 8.3] for patients treated with chemotherapy. The analysis of OS for patients treated with BESPONSA compared to chemotherapy did not meet the pre-specified boundary for statistical significance (HR: 0.75 [97.5% CI: 0.57-0.99]).1
The U.S. labeling for BESPONSA includes a boxed warning for hepatotoxicity, including hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), and increased risk of post-HSCT non-relapse mortality. Veno-occlusive disease, including fatal and life-threating VOD, occurred in 14 percent of patients treated with BESPONSA. A higher post-HSCT non-relapse mortality rate occurred in patients treated with BESPONSA (39%) than chemotherapy (23%).1 In patients treated with BESPONSA, the most common (≥20%) adverse reactions were thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyltransferase increased, and hyperbilirubinemia.1
Pfizer is committed to helping patients gain access to Pfizer medicines, including BESPONSA, and related educational tools, resources and services, regardless of their financial or health insurance status through the company’s patient assistance programs. Patients can call 1-877-744-5675 to learn more.
The full Prescribing Information, including BOXED WARNING, for BESPONSA can be found at View Source
IMPORTANT BESPONSA (inotuzumab ozogamicin) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
WARNING: HEPATOTOXICITY, INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE (VOD) (ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME) and INCREASED RISK OF POST–HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) NON-RELAPSE MORTALITY (NRM):
Hepatotoxicity, including fatal and life-threatening VOD, occurred in patients who received BESPONSA. The risk of VOD was greater in patients who underwent HSCT after BESPONSA treatment. Consider identified risk factors. Monitor closely for signs and symptoms of VOD
There was a higher post-HSCT non-relapse mortality rate in patients receiving BESPONSA, resulting in a higher Day 100 post-HSCT mortality rate
Hepatotoxicity, Including VOD:
Hepatotoxicity, including fatal and life-threatening VOD, occurred in patients who received BESPONSA. The risk of VOD was greater in patients who underwent HSCT after BESPONSA treatment. The use of HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin ≥ the upper limit of normal (ULN) before HSCT were significantly associated with an increased risk of VOD. Other risk factors for VOD in patients treated with BESPONSA included ongoing or prior liver disease, prior HSCT, increased age, later salvage lines, and a greater number of BESPONSA treatment cycles. Grade 3/4 increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin have occurred.
Monitor closely for signs and symptoms of VOD; these may include elevations in total bilirubin, hepatomegaly (which may be painful), rapid weight gain, and ascites. Elevation of liver tests may require dosing interruption, dose reduction, or permanent discontinuation of BESPONSA. Permanently discontinue treatment if VOD occurs. If severe VOD occurs, treat according to standard medical practice.
Increased Risk of Post-HSCT Non-Relapse Mortality: There was a higher post-HSCT non-relapse mortality rate in patients receiving BESPONSA, resulting in a higher Day 100 post-HSCT mortality rate. In the BESPONSA arm, the most common causes of post-HSCT non-relapse mortality included VOD and infections. Monitor closely for toxicities post HSCT, including signs and symptoms of infection and VOD.
Myelosuppression: Myelosuppression, and severe, life-threatening and fatal complications of myelosuppression, including hemorrhagic events and infections, have occurred with BESPONSA. Thrombocytopenia, neutropenia, and febrile neutropenia were reported.
Monitor complete blood counts prior to each dose of BESPONSA and monitor for signs and symptoms of infection, bleeding/hemorrhage, or other effects of myelosuppression during treatment and provide appropriate management. As appropriate, administer prophylactic anti-infectives during and after treatment with BESPONSA. Dose interruption, dose reduction, or permanent discontinuation may be required.
Infusion-Related Reactions: Infusion-related reactions have occurred in patients who received BESPONSA. Premedicate with a corticosteroid, antipyretic, and antihistamine prior to dosing. Monitor patients closely during and for at least 1 hour after the end of the infusion for the potential onset of infusion-related reactions. Interrupt the infusion and institute appropriate medical management if an infusion-related reaction occurs. For severe or life-threatening infusion reactions, permanently discontinue BESPONSA.
QT Interval Prolongation: Increases in QT interval have occurred. Administer BESPONSA with caution in patients who have a history of or predisposition to QTc prolongation, who are taking medicinal products that are known to prolong QT interval, and in patients with electrolyte disturbances. Obtain electrocardiograms and electrolytes prior to treatment and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
Embryo-Fetal Toxicity and Nursing Mothers: BESPONSA can cause embryo-fetal harm. Advise males and females of reproductive potential to use effective contraception during BESPONSA treatment and for at least 5 and 8 months after the last dose, respectively. Advise women against breastfeeding while receiving BESPONSA and for 2 months after the last dose.
Adverse Reactions: The most common (≥20%) adverse reactions observed with BESPONSA were thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyltransferase increased, and hyperbilirubinemia.
The most common (≥2%) serious adverse reactions were infection, febrile neutropenia, hemorrhage, abdominal pain, pyrexia, VOD, and fatigue.
Please see full Prescribing Information, including BOXED WARNING here View Source
About Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia with a poor prognosis in adults.2 The current foundational treatment is intensive, long-term chemotherapy.3 In 2017, it is estimated that 5,970 cases of ALL will be diagnosed in the United States.4 About 4 in 10 cases occur in adults.4 While about 80-90% of adult patients will have a complete remission at some point during initial treatment, the remainder (approximately 10%-20%) will be refractory, meaning they no longer respond to treatment.3 Additionally, about half of patients who achieve remission will relapse.3 The post relapse median survival is 4.5 to 6 months.5
About BESPONSA (inotuzumab ozogamicin)
BESPONSA is an antibody-drug conjugate (ADC) composed of a monoclonal antibody (mAb) targeting CD22, a cell surface antigen expressed on cancer cells in almost all B-ALL patients, linked to a cytotoxic agent.6 When BESPONSA binds to the CD22 antigen on B-cells, it is internalized into the cell, where the cytotoxic agent calicheamicin is released causing cell death.7 BESPONSA is administered as a one-hour intravenous infusion that can be given in the outpatient setting of care for appropriate patients.
BESPONSA originates from a collaboration between Pfizer and Celltech, now UCB. Under the terms of this agreement, Pfizer has sole responsibility for all commercialization, manufacturing and clinical development activities for this molecule. Pfizer also collaborated with SFJ Pharmaceuticals Group on the registrational program (INO-VATE ALL) for BESPONSA.