The recent first global approval of inotuzumab ozogamicin has been reviewed in detail in the First Global Approval report in Adis’ journal Drugs[1], based on the development milestones tracked in AdisInsight[2].

In June 2017, inotuzumab ozogamicin (Besponsa®), developed by Pfizer, received its first global approval in the Europe as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL). This includes use in adult patients with Philadelphia chromosome-positive, relapsed or refractory CD22-positive B-cell precursor ALL; but is restricted to those who have failed treatment with at least one tyrosine kinase inhibitor.[3]

Inotuzumab ozogamicin is an intravenous anti-CD22 monoclonal antibody-calicheamicin conjugate that binds to CD22-expressing tumour cells. Subsequent to binding, the cytotoxic calicheamicin derivative is released inside the cell, causing double-strand DNA breakage, resulting in cell death. [1]

The European approval was based on results from the phase 3 INO-VATE trial[4] , and in August, a few weeks after this approval, inotuzumab ozogamicin was also approved in the US for the treatment of adults with relapsed or refractory B-cell precursor ALL, after it was reviewed under the Orphan Drug and Breakthrough Therapy designations and Priority Review Program.[5] [6]

In adults, ALL is considered a rare disease. According to the European Society for Medical Oncology (ESMO) the annual incidence of ALL in Europe is 1.28 per 1000,000 individuals, but there are marked differences depending on age range: e.g. 0.53 for the range 45-54 years, and almost doubling to 1.0 for the range 55-74 years.[7] The American Cancer Society, forecasts that there will be 5,970 new cases of ALL in the US in 2017, of which 1,440 (24%) will be fatal.[8]

Inotuzumab ozogamicin carries a black boxed warning for hepatotoxicity, including hepatic veno-occlusive disease (VOD), which also known as sinusoidal obstruction syndrome (SOS), as well as the increased risk of post-hematopoietic stem cell transplant (HSCT) non-relapse mortality. [5] [6]

Professor David Marks, Department of Hematology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK, described recurrent ALL that is refractory to first-line therapy as “a rare and rapidly progressive disease with poor prognosis.” He went on to explain that, “The approval of BESPONSA (inotuzumab ozogamicin) provides a much needed treatment option, for physicians and patients alike, that may help improve outcomes for some of the most vulnerable leukemia patients in Europe.”[9]

Inotuzumab ozogamicin is also under phase I/II development for chronic myeloid leukaemia (CML), and phase I development for Burkitt’s lymphoma in the US[2].

For further information related to the first approval of inotuzumab ozogamicin please visit Drugs[1], or to learn more about the overall development of inotuzumab ozogamicin across all indications visit AdisInsight[2].

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