Orphan Drug Designation granted to tinostamustine in EU for very rare form of leukaemia

Image of two small people signing and over-sized contract with rubber stamp at side to show Orphan Drug Designation granted to tinostamustine in EU for very rare form of leukaemia

Mundipharma has announced that the European Commission (EC) has now adopted the European Medicines Agency (EMA) Committee for Orphan Medicinal Products recommendation to grant Orphan Drug Designation to tinostamustine, an alkylating histone-deacetylase inhibiting molecule, for the treatment of T-cell prolymphocytic leukaemia (T-PLL).3

The EMA considers Orphan Drug Designation (ODD) status for medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than five per 10,000 people in the EU.4

T-PLL is an extremely rare and typically aggressive leukaemia.5,6 It affects approximately 2% of all patients with mature lymphocytic leukaemias1 and affects older adults with a median age at diagnosis of 61 years. It is more common in men than in women.2 T-PLL is characterised by the out-of-control growth of mature T-cells (T-lymphocytes). T-cells are a type of white blood cell that protects the body from infections.2 Due to its rarity, T-PLL can be misdiagnosed, resulting in poor patient outcomes.5 The condition is life-limiting and chronically debilitating, with fewer than 5% of patients surviving to five years from diagnosis.7 T-PLL generally progresses rapidly and does not respond well to standard multi-agent chemotherapy, with relapses being a common occurrence.5,6

Brian Sheehan, Chief Scientific Officer, Mundipharma Research added: “Orphan drug designation is an important milestone in the development of tinostamustine, which is currently in early phase clinical trials. We are proud of our commitment to helping patients with rare and difficult-to-treat cancers, such as T-PLL, where therapeutic options are so limited and patients have a clear need for new therapies.”

The EC decision adopting the EMA opinion follows that of the FDA, which granted tinostamustine ODD status for the treatment of T-PLL in March 2019.

Tinostamustine, is an alkylating histone-deacetylase inhibiting molecule in early phase clinical development for a range of rare and difficult-to-treat blood cancers and advanced solid tumours. Preclinical studies have shown that tinostamustine has the potential to improve access to the DNA strands within cancer cells, break them and counteract damage repair.8-11 The preclinical data also suggest that these complementary and simultaneous modes of action have the potential to overcome resistance towards some other cancer treatments.8-11


  1. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition) IARC: Lyon 2017 (pg 272)
  2. T-cell prolymphocytic leukemia (T-PLL) information page. Leukemia and Lymphoma Society. Available at: https://www.lls.org/leukemia/t-cell-prolymphocytic-leukemia-t-pll. Last accessed 8 July 2020.
  3. European Commission Community Register of orphan medicinal products. Available at: https://ec.europa.eu/health/documents/community-register/html/o2307.htm Last accessed 3 August 2020.
  4. EMA Sponsors Guide to an Orphan Designation https://www.ema.europa.eu/en/human-regulatory/research-development/orphan-designation/applying-orphan-designation Last accessed 8 July 2020.
  5. Dearden C. How I treat prolymphocytic leukemia. Blood. 2012; 120(3):538–55.
  6. Laribi K, Lemaire P, Sandrini J et al. Advances in the understanding and management of T-cell prolymphocytic leukemia. Oncotarget 2017; 8(61):104664–104686.
  7. Hopfinger G, Busch R, Pflug N et al. Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia. Cancer 2013; 119:2258-67.
  8. López-Iglesias AA. The Alkylating Histone Deacetylase Inhibitor Fusion Molecule Edo-S101 Displays Full Bi-Functional Properties in Preclinical Models of Hematological Malignancies. Blood 2014; 124: (21). https://ash.confex.com/ash/2014/webprogram/Paper72121.html
  9. López-Iglesias AA. preclinical antimyeloma activity of EDO-S101 (bendamustine-vorinostat fusion molecule) through DNA-damaging and HDACi effects. 15th International Myeloma Workshop. 23−26 September 2015. Rome, Italy.
  10. Di Filippi R, et al. The First-In-Class Alkylating Histone Deacetylase Inhibitor (HDACi) Fusion Molecule EDO-S101 Exerts Potent Preclinical Activity Against Tumor Cells of Hodgkin Lymphoma (HL) Including Bendamustine Resistant Clones. 57th Annual Meeting and Exposition of the American Society of Hematology (ASH), 6 December 2015.
  11. Yan S, Xu K, Lin J, et al. Synergistic inhibition of tumor growth and overcoming chemo-resistance by simultaneously targeting key components in DNA damage/repair, epigenetic, and putative cancer stem cell signaling pathways using novel dual-functional DNA-alkylating/HDAC inhibitor and tumor suppressor gene nanoparticles in lung cancer. Cancer Research 2012;72(Suppl 1): Abstract 2741.