STAMFORD, Conn.--(BUSINESS WIRE)--Imbrium Therapeutics L.P., a clinical-stage biopharmaceutical company and operating subsidiary of Purdue Pharma L.P., in conjunction with Mundipharma EDO GmbH, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to its investigational drug tinostamustine, a potentially first-in-class alkylating deacetylase inhibiting molecule being studied in early phase clinical trials, for the treatment of T-cell prolymphocytic leukemia (T-PLL).
T-PLL is an extremely rare and aggressive T-cell leukemia that is characterized by out of control growth of mature T-cells. There are very limited effective treatment options for T-PLL. The disease typically progresses rapidly and does not respond well to standard multi-agent chemotherapy.
“This orphan drug designation represents an important step not just for Imbrium and the development of tinostamustine, but also for the patients suffering from T-PLL who do not currently have sufficient treatment options,” said Richard Fanelli, PhD, head of Regulatory Affairs, Imbrium Therapeutics.
The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Orphan drug designation is intended to facilitate drug development for rare diseases and may provide certain incentives to drug developers.1,2 T-PLL is an extremely rare and typically aggressive blood cancer. It is so rare that healthcare professionals may only see one case of T-PLL every five to 10 years.3 Due to its rarity, T-PLL can be misdiagnosed, resulting in poor patient outcomes with a median survival of around one year. 3,4 There is no guarantee that tinostamustine, an investigational agent, will successfully complete clinical development or gain FDA approval.
Craig Landau, MD, president and CEO, Purdue Pharma L.P. added, “This marks the second orphan drug designation we have received from the U.S. FDA in just the last two months and demonstrates our commitment to rapidly advancing our pipeline of oncology chemotherapeutics for rare and difficult to treat cancers.”
In addition to T-PLL, Imbrium Therapeutics has initiated the early phase clinical development of tinostamustine in a range of rare and difficult-to-treat blood cancers and advanced solid tumors.
About T-cell prolymphocytic leukemia
T-cell prolymphocytic
leukemia (T-PLL) affects approximately 2 percent of all patients with
mature lymphocytic leukemias.5 It is characterized 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.6 The
majority of patients present with hepatosplenomegaly and generalized
lymphadenopathy, with skin infiltration, anemia and thrombocytopenia
often seen.5 T-PLL affects older adults with a median age at
diagnosis of 61 years, and it is more common in men than in women.6
T-PLL typically has rapid progression and does not respond well to standard multi-agent chemotherapy.
About tinostamustine
Tinostamustine (EDO-S101), is a novel
multi-action therapy in Phase 2 clinical development for a range of rare
and difficult-to-treat blood cancers and advanced solid tumors.
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.7,8,9,10 The preclinical data also suggest that these complementary and simultaneous modes of action have the potential to overcome resistance toward some other cancer treatments.7,8,9,10
Tinostamustine is currently being studied in multiple myeloma, Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, T-cell prolymphocytic leukemia, soft tissue sarcoma, small cell lung cancer, triple-negative breast cancer, ovarian cancer, endometrial cancer and MGMT-unmethylated glioblastoma.
About Imbrium Therapeutics
Imbrium is a clinical-stage
biopharmaceutical company dedicated to advancing medical science through
the development of important new pharmacologic and biologic
therapeutics. We are pursuing oncology chemotherapeutics, treatments for
disorders of the central nervous system, and non-opioid approaches to
the management of pain. As an operating subsidiary of Purdue Pharma
L.P., Imbrium strives to develop and bring to market new medicines that
serve the unmet needs of patients, physicians and health systems
worldwide. We have built a robust and diversified pipeline of
investigational drug candidates, and we actively collaborate with
industry and academic partners to identify and advance future impactful
medicines. For more information, please visit: www.imbriumthera.com.
About Mundipharma EDO
Mundipharma EDO is part of the
Mundipharma global network of privately-owned independent associated
companies, which operate in over 120 countries worldwide. We develop
treatments for patients around the world with rare or
relapsed/refractory cancer, investigating smart approaches to new cancer
treatments from concept through to clinical development and regulatory
approval.
We operate a lean, agile research and development model, empowering the team to form conclusions and make quick decisions with the aim of getting new therapies to patients as rapidly as possible. For more information please visit: www.edoncology.com.
1 U.S. Food & Drug Administration. Designating an Orphan
Product: Drugs and Biological Products. Last updated Jul 2018. Accessed
Mar 25, 2019. Retrieved from https://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/default.htm.
2
U.S. Government Publishing Office. Electronic Code of Federal
Regulations. 316.21: Verification of orphan-drug status. Accessed Mar
25, 2019. Retrieved from https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=718f6fcbc20f2755bd1f5a980eb5eecd&mc=true&n=sp21.5.316.c&r=SUBPART&ty=HTML#se21.5.316_120.
3
Dearden C. How I treat prolymphocytic leukemia. Blood. 2012;
120(3):538–551. Accessed Mar 25, 2019. Retrieved from http://www.bloodjournal.org/content/bloodjournal/120/3/538.full.pdf.
4
National Institutes of Health. National Cancer Institute SEER Database:
T-cell prolymphocytic leukemia. Accessed Mar 25, 2019. Retrieved from https://seer.cancer.gov/seertools/hemelymph/51f6cf58e3e27c3994bd53f3/.
5
Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic
and Lymphoid Tissues (Revised 4th Edition). IARC: Lyon, 2017.
6
Leukemia and Lymphoma Society. T-cell Prolymphocytic Leukemia (T-PLL).
Accessed Mar 25, 2019. Retrieved from https://www.lls.org/leukemia/t-cell-prolymphocytic-leukemia-t-pll.
7
Loìpez-Iglesias AA, et al. The Alkylating Histone Deacetylase Inhibitor
Fusion Molecule Edo-S101 Displays Full Bi-Functional Properties in
Preclinical Models of Hematological Malignancies. Blood. 2014;
124:2100.
8 Loìpez-Iglesias AA, et al. Preclinical
Antimyleoma Activity of EDO-S101. Clinical Lymphoma, Myeloma &
Leukemia. 2015; 15(Suppl 3):PO-238.
9 De 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. Blood. 2015; 126:2481.
10
Yan S 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 Res
2012;72(8 Suppl):Abstract nr 2741. Accessed Mar 25, 2019. Retrieved from http://cancerres.aacrjournals.org/content/72/8_Supplement/2741.