Swedish Orphan Biovitrum (Sobi®) has signed an exclusive license agreement with ADC Therapeutics to develop and commercialize loncastuximab tesirine (Zynlonta®) for use in hematologic and other indications of large unmet medical need in Europe and most international markets.
Under the terms of the license agreement, Sobi has been granted rights to develop and commercialise loncastuximab tesirine for all hematologic and solid tumour indications outside of the United States, greater China, Singapore and Japan. Sobi will pay US $ 55 million in an upfront payment, to be financed by Sobi’s cash reserves, and US $ 50 million following EU regulatory approval in 3rd-line Diffuse large B-cell lymphoma (DLBCL), an aggressive, malignant, orphan disease in hematology with an incidence in Europe of approximately 4 cases per 100,000 adults per year. [1]
The U.S. Food and Drug Administration (FDA) has approved loncastuximab tesirine-lpyl for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma.In addition, Sobi will pay royalties from mid-teens to mid-twenties per cent of net sales and up to approximately US $ 330 million in potential regulatory and sales milestones. As loncastuximab tesirine is in development for other indications, Sobi will contribute 25 per cent of the direct development costs up to a cap of US $ 10 million per year. ADC Therapeutics is responsible for clinical development and product supply to Sobi.
Loncastuximab tesirine
Loncastuximab tesirine is an antibody-drug conjugate (ADC) against CD19, a protein expressed on the surface of B cells. Once bound to a CD19-expressing cell, loncastuximab tesirine is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.
The medicine has orphan drug designation in the European Union and is under regulatory review with a decision anticipated in the first quarter of 2023.
The U.S. Food and Drug Administration (FDA) has approved loncastuximab tesirine-lpyl for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma.
Ameet Mallik joined ADC Therapeutics as CEO in May 2022.The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to 1st-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with loncastuximab tesirine. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Loncastuximab tesirine is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.
License agreement
The license agreement for loncastuximab tesirine aims at augmenting Sobi’s presence in orphan diseases within hematology, one of Sobi’s two main disease areas.
Loncastuximab tesirine will expand Sobi’s offering to patients with debilitating orphan diseases in hematology and is anticipated to be made commercially available alongside other Sobi hematology medicines, including avatrombopag (Doptelet®), an orally administered thrombopoietin receptor agonist (TPO-RA) that mimics the biologic effects of TPO in stimulating the development and maturation of megakaryocytes, resulting in increased platelet count.
Guido Oelkers, Ph.D., is the Chief Executive Officer of Swedish Orphan Biovitrum since 2017.“Based on our commitment to provide innovative medicines that transform the lives of people with rare and debilitating diseases as well as our stated capital-allocation priorities, we are pleased to announce the license agreement with ADC Therapeutics for loncastuximab tesirine in Europe and most international markets,” said Guido Oelkers, Chief Executive Officer of Sobi.
“We believe Sobi’s heritage and strong presence in haematology coupled with new medicines like avatrombopag will provide a competitive platform for bringing loncastuximab tesirine to more patients with orphan diseases,” Oelkers added
Establishing a partnership
“We are thrilled to establish this important partnership with Sobi to continue expanding our global reach to bring loncastuximab tesirine to as many patients as possible worldwide. Sobi has a strong global commercial infrastructure, proven capabilities in the areas of haematology and rare diseases, and importantly, shares our passion for improving the lives of patients,” concluded Ameet Mallik, Chief Executive Officer of ADC Therapeutics.
Highlights of prescribing information
Loncastuximab tesirine (Zynlonta®) [Prescrtibing Information]
Avatrombopag (Doptelet®)[Prescribing information]
References
[1] Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, Marcos-Gragera R, Maynadié M, Simonetti A, Lutz JM, Berrino F; HAEMACARE Working Group. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010 Nov 11;116(19):3724-34. doi: 10.1182/blood-2010-05-282632. Epub 2010 Jul 27. Erratum in: Blood. 2011 Mar 24;117(12):3477. PMID: 20664057.
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