Positive Phase 1 data for Promitil

LipoMedix announces publication of positive Phase 1 data for Promitil in Investigational New Drugs

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JERUSALEM—LipoMedix Pharmaceuticals, an oncology-focused pharmaceutical company, has announced that Phase 1 data of Promitil (PL-MLP) in patients with metastatic colorectal cancer (CRC) was published in the Investigational New Drugs research journal. The study, entitled “Pharmacokinetics of mitomycin-c lipidic prodrug entrapped in liposomes and clinical correlations in metastatic colorectal cancer patients,” demonstrated positive results on the pharmacokinetics and clinical observations of the drug.
LipoMedix has developed a pegylated liposome delivery platform based on the encapsulation of a new chemical entity (NCE) known as mitomycin-c lipidic prodrug (MLP), a proprietary prodrug form of the anticancer agent mitomycin-c. Promitil enables efficient and selective tumor delivery of MLP, with rapid activation to a powerful mitomycin-c metabolite. The drug candidate has low toxicity and is active against a broad variety of cancer types in animal models, including colorectal, gastric, pancreatic and multi-drug resistant tumors.
“The treatment of metastatic colorectal cancer has undergone major advances yielding significant improvements in survival over the past two decades, yet remains disappointing in pre-treated patients with advanced stage cancer. The development of Promitil represents a novel and smart tool to overcome the problems associated with mitomycin-c toxicity with an optimized liposomal delivery system reducing normal tissue exposure and enhancing cancer tissue uptake,” said Sanjeev Luther, chairman of the Board of LipoMedix.  
The Phase 1 study analyzed 53 patients with advanced, treatment-refractory CRC. The patients were treated with Promitil either as a single agent, or in combination with capecitabine and/or bevacizumab. Promitil was well tolerated with a good safety profile, as previously reported.
Treatment resulted in a substantial rate of disease stabilization, reported in 15 out of 36 efficacy-evaluable patients (42%). Prolonged survival of stable disease patients was also observed, with a median survival of 14.4 months — significantly longer than of progressive disease patients (6.5 months) and non-evaluable patients (2.3 months).
“MLP pharmacokinetics was stealth-like with long T½ (~1 day), slow clearance, and small volume of distribution (Vd). The addition of capecitabine and/or bevacizumab did not have any apparent effect on the pharmacokinetics of MLP and clinical outcome. High baseline neutrophil count and CEA level were correlated with faster clearance, and larger Vd,” points out the article abstract. “Stable disease patients had longer T½ and slower clearance than other patients. T½ and clearance were significantly correlated with survival … The correlation of neutrophil count and CEA level with pharmacokinetic parameters of MLP is an unexpected finding that needs further investigation.” 
A long circulating half-life of Promitil was associated with stable disease and longer survival. This finding is consistent with the enhanced tumor localization of long circulating liposomes that could result in improved disease, and underscores the relevance of personalized pharmacokinetic evaluation in the use of nanomedicines. 
“Treatment of metastatic colorectal cancer after failure to standard chemotherapy is a frequent and unmet need in oncology,” noted Dr. Alberto Gabizon, president and chief scientific officer of LipoMedix. “The lipidic prodrug of mitomycin-c entrapped in liposomes is an important step towards maximizing survival benefits in this difficult condition. Further, the results of the current study suggest ways that could predict treatment outcome soon after treatment is initiated and help select patients that will benefit from Promitil.”

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