Type of information: Granting of a Market Authorisation in the US
Product name: Besponsa®
Compound: inotuzumab ozogamicin
Therapeutic area: Rare diseases - Cancer - Oncology
- antibody drug conjugate. Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) comprised of a monoclonal antibody targeting CD22, a cell surface antigen expressed on approximately 90 percent of B-cell malignancies, linked to a cytotoxic agent. When inotuzumab ozogamicin binds to the CD22 antigen on malignant B-cells, it is absorbed into the cell, at which point the cytotoxic agent calicheamicin is released to destroy the cell.
- Inotuzumab ozogamicin 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.
Company: Pfizer (USA - NY)
Disease: relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia
- • On August 17, 2017, Pfizer announced that the FDA has approved Besponsa® (inotuzumab ozogamicin) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Besponsa® was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs.
- 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. 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 (lips) 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 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]).
- 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.
• On June 30, 2017, Pfizer announced that the European Commission has approved Besponsa® (inotuzumab ozogamicin) as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL). This indication includes treatment of adults with Philadelphia chromosome positive (Ph+) as well as Philadelphia chromosome negative (Ph-) relapsed or refractory B-cell precursor ALL. Adults with Ph+ relapsed or refractory CD22-positive B-cell precursor ALL should have failed treatment with at least one tyrosine kinase inhibitor (TKI).
- • On April 21, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Besponsa® (inotuzumab ozogamicin) intended for the treatment of adults with acute lymphoblastic leukaemia. Besponsa® will be available as a 1-mg powder for concentrate for solution for infusion. Besponsa® has been shown to increase the proportion of patients who have complete remission and molecular remission and to delay the progression of disease. The most common side effects are
thrombocytopenia, neutropenia, anaemia, leucopenia, infection, haemorrhage and venoocclusive liver
disease/sinusoidal obstruction syndrome.
The full indication is: "Besponsa® is indicated as monotherapy for the treatment of adults with relapsed or
refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). Adult patients with Philadelphia chromosome positive (Ph+) relapsed or refractory B cell precursor ALL should have failed treatment with at least 1 tyrosine kinase inhibitor (TKI)". If approved, Besponsa® will be the first antibody drug conjugate available for patients with this type of leukemia.The positive opinion was based on results from the Phase 3 INO-VATE 1022 trial, which enrolled 326 adult patients with relapsed or refractory B-cell ALL, and compared Besponsa® to standard of care chemotherapy. The INO-VATE 1022 study had two primary endpoints, complete response with or without hematologic remission (CR/CRi) and overall survival (OS). Results from the trial were published in The New England Journal of Medicine in June 2016.
- A Biologics License Application (BLA) for Besponsa® for the treatment of adult patients with relapsed or refractory B-cell precursor ALL has been accepted for filing and granted Priority Review by the FDA. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in August 2017.
- • On October 19, 2015, Pfizer announced that inotuzumab ozogamicin received Breakthrough Therapy designation from the FDA for acute lymphoblastic leukemia (ALL). The Breakthrough Therapy designation was based on the results of the Phase 3 INO-VATE ALL trial, which enrolled 326 adult patients with relapsed or refractory CD22-positive ALL and compared inotuzumab ozogamicin to standard of care chemotherapy. Topline results from the trial were announced in April 2015 and also presented at the 20th Congress of the European Hematology Association (EHA).
- • On 16-17 april 2013, the Committee for Orphan Medicinal Products (COMP) has recommended the granting of an orphan designation for inotuzumab ozogamicin for treatment of B-cell acute lymphoblastic leukaemia.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-08-17
UE authorization: 2017-06-30
Favourable opinion UE: 2017-04-21
Favourable opinion USA:
Orphan status USA: 2013-03-25
Orphan status UE: 2013-06-07
Pediatric exclusivit _USA:
Pediatric exclusivity UE: