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Home > Research & Development > Central
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> KRN5500
Product/Technology Name: KRN5500 (6-[4-Deoxy-4-[(2E,4E)-tetradecadienoylglycyl]amino
-L-glycero-ß-L-manno-heptopyranosyl]amino-9H-purine)
Condition/Disease Targeted: Neuropathic Pain in cancer patients, in particular, chemotherapy-induced peripheral neuropathy (CIPN)
Company: DARA Therapeutics, Inc
Purpose: KRN5500 is a novel spicamycin derivative produced by Streptomyces alanosinicus and is available as a solution for intravenous (IV) administration. KRN5500 was discovered in an effort to identify new agents that induced differentiation of myeloid leukemia cells.
Product Development: Safety and efficacy data from Phase I trials have been leveraged to support DARA Therapeutics’ active IND and ongoing Phase 2a clinical trial. The objective of this Phase 2a feasibility study is to determine the potential of KRN5500 (a spicamycin analogue) to be a breakthrough medicine for the treatment of neuropathic pain in cancer patients.
Viability: The basis for conducting the Phase 2a study is founded on several cases and studies:
- An oncology patient with a 26 year history of neuropathic pain received a single i.v. infusion that resulted in dramatic and total pain relief. That relief was effectively maintained for the remaining 7 months of his life in which treatment (6 dose courses) was given in the first 4 months. [Ref: Borsook, D. & Edwards, A.D. (2004) Pain Medicine 5(1):104-108]
- Researchers found significant efficacy in three animal models of neuropathic pain and lack of efficacy in a model of nociceptive pain. [Refs: Abdi et.al (2000) Anesthes. Analg. 91:955-959; DiLorenzo et.al. (2002) Neurosci. Lett. 330:37-40; Kobierski et.al. (2003) Anesthes.Analg. 97:174-182]
- Extremely long-lasting effect after single dosing was recorded in animal neuropathic pain models, mirroring what was observed in the human patient mentioned above (similar pharmacokinetic/pharmacodynamic relationship). [Refs: Abdi et.al (2000) Anesthes. Analg. 91:955-959; DiLorenzo et.al. (2002) Neurosci. Lett. 330:37-40; Kobierski et.al. (2003) Anesthes.Analg. 97:174-182]
Four clinical trials have been conducted in cancer patients, including one in Japan and 3 in the United States. Three of these studies are complete; the fourth was closed to patient accrual and treatment in December 2004. A total of 91 patients with solid tumors have been treated with single IV KRN5500 doses of up to 21 mg/m2 and weekly doses of up to 42 mg/m2. While KRN5500 has not shown anti-cancer efficacy in any trial, its use in pain elimination is encouraging. |
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KRN5500