Lansoprazole, the commonly used anti-ulcer drug, is currently being studied as treatment for liver cancer by MexMed.
NexMed, Inc, a specialty CRO with a pipeline of products based on the NexACT technology, announced that the U.S. Food & Drug Administration has cleared the company to proceed with the proposed Phase 2 trial of PrevOnco, its proprietary cancer treatment for patients with advanced, unresectable hepatocellular carcinoma (HCC), or liver cancer.
PrevOnco incorporates lansoprazole, which is the generic anti-ulcer compound approved under the name Prevacid and marketed in the U.S. by Takeda Pharmaceuticals North America, Inc.
In vitro and in vivo data generated to date has demonstrated the ability of lansoprazole to inhibit tumor cell growth and enhance survival in mouse models of cancer alone, and in combination with Doxorubicin.
US FDA granted PrevOnco orphan drug status in August 2008, and in March 2010, NexMed filed its Investigational New Drug (IND) application for the product candidate.
US FDA has given NexMed the opportunity to move PrevOnco™ directly into a Phase 3 trial that would support marketing approval, subject to positive study results.
In order to pursue this regulatory path, NexMed would need to expand the proposed Phase 2 study design to use PrevOnco in combination with Doxorubicin as a second-line therapy for patients who have failed Nexavar, the currently marketed first-line anticancer treatment for patients with either HCC or advanced renal cell carcinoma (cancer of the kidney).
“We are very pleased that the FDA agreed with our protocol for the HCC Phase 2 trial for PrevOnco™ as a first-line therapy for HCC. Additionally, we are actively assessing the suggestion made by the FDA to move directly into a Phase 3 trial, by studying PrevOnco™ in combination with Doxorubicin as a second-line therapy for patients who have failed NEXAVAR® therapy. Following this path could be very advantageous for NexMed since advancing the drug directly into a Phase 3 study would save us at least 12-24 months in development time,” stated Dr Bassam Damaj, president and chief executive officer of NexMed.
NexMed’s prospective, open label, single-arm, multicenter Phase II trial will assess the safety and efficacy of lansoprazole and doxorubicin in patients with advanced unresectable HCC at up to 10 study sites throughout the U.S. The primary objective of the study is to assess the response rate to doxorubicin and lansoprazole.
Subjects will be treated with oral lansoprazole 90mg twice daily and intravenous (IV) doxorubicin 60 mg/m2 administered every 21 days.
Subjects will continue to receive IV doxorubicin plus lansoprazole, if tolerated, up to a maximum of six consecutive cycles of doxorubicin, as long as there is no evidence of progressive disease. A total of between 15 and 70 subjects are expected to be enrolled in the study for a period of up to 12 months in the absence of disease progression or intolerance.
Total study duration is anticipated to be one to three years, depending on the rate of enrollment and number of patients enrolled.
NexMed’s drug delivery technology – NexACT – represents an important breakthrough in providing a highly effective transdermal therapeutic approach to the diseases that are currently being treated by systemic (oral or intravenous injections) therapy.
The patented NexACT technology utilizes highly effective formulations containing new biodegradable ingredients to overcome the skin’s natural barrier properties and enables the rapid penetration of high concentrations of active drug directly through the skin and major mucous membranes, thereby resulting in new and highly effective topical and transdermal therapies.
NexACT technology may offer significant clinical benefits if low bioavailability, multiple daily dosing, liver first pass effect, or gastrointestinal side effects are associated with oral or injectable dosage forms.
For drugs with narrow therapeutic index, NexACT technology may provide a controlled rate of administration which is a significant advantage for maintaining efficacy while reducing toxicity.
Using differential scanning calorimetry, NexACT technology is suggested to enhance drug transfer by interacting with the polar region of the phospholipid bilayer and also by increasing the motional freedom of lipid hydrocarbon chains.
The cellular mechanism of action of NexACT technology is shown to increase the permeability of cell membrane in a time and concentration dependent manner. Novel application of NexACT technology for transcellular drug delivery is under development.
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world, with a high incidence in China and other Asian countries.
Although uncommon in the U.S., there are a reported 8,500 to 11,000 new cases diagnosed each year, comprising 2% of all malignancies. Cases in the U.S. occur primarily in men of Chinese descent, a subpopulation which has a high incidence of viral hepatitis – a known risk factor for HCC.