NexMed Receives FDA Clearance for PrevOnco Phase 2 Study as First-Line Therapy for HCC

NexMed, Inc. , a specialty CRO with a pipeline of products based on the NexACT technology, today announced that the U.S. Food & Drug Administration (FDA) 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.

The FDA granted PrevOnco orphan drug status in August 2008, and in March 2010, NexMed filed its Investigational New Drug application for the product candidate.

The Company also noted that in IND review communication, the 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).

PrevOnco incorporates lansoprazole, which is the generic anti-ulcer compound approved under the name Prevacid(R) 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.

Commenting on today's news, Dr. Bassam Damaj, President and Chief Executive Officer of NexMed, stated, "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."

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Pfizer liver cancer trial halted on safety concern

Pfizer Inc said on Thursday it has discontinued a late stage liver cancer study of its drug Sutent because of high incidence of serious adverse events suffered by patients taking the medicine.
Following a review by the independent Data Monitoring Committee the trial was halted over safety issues, Pfizer said.

Sutent is already approved to treat advanced kidney cancer and gastrointestinal stromal tumors following disease progression and had worldwide sales of $964 million in 2009.

Pfizer is testing Sutent against a wide range of cancers in hopes of significantly expanding sales of the drug.

The liver cancer failure represents the latest in a long list of clinical setbacks for the world's largest drugmaker, including a Sutent failure in a late stage advanced breast cancer study announced last month.

The company has been widely criticized by analysts for its inability to deliver products based on its own research despite the industry's largest research and development budget.

The company last year acquired Wyeth for $67 billion in large part to gain that company's promising portfolio of drugs in development.

The halted open label trial tested Sutent against Nexavar, a liver cancer drug sold by Bayer AG and Onyx Pharmaceuticals Inc .

Safety monitors found higher incidence of serious side effects in patients taking Sutent, known chemically as sunitinib, compared with those who received Nexavar.

Sutent also failed to demonstrate that it was either superior or non-inferior to Nexavar in extending the survival of liver cancer patients, the company said.

"The disappointing outcome of this trial challenges all of us to work harder to understand the complex biology of this disease," Mace Rothenberg, head of clinical development for Pfizer's oncology unit, said in a statement.

Pfizer is still testing the drug against non-small cell lung cancer, prostate cancer and for kidney cancer following surgery.

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Targeting Tumor Behavior May Lead To New Liver Cancer Drugs

Ohio State University cancer researchers have used computational and genomic methods to identify possible anti-cancer agents that may block a particular kind of tumor behavior. The agents target multiple genes associated with that behavior at one time.

The researchers wanted to find agents that might reverse the gene changes associated with invasive liver cancer and perhaps stop liver tumors from spreading in the body. Such therapy could greatly improve patient survival, the researchers say.

The findings are published online in the journal Cancer.

“This is an exciting new way to find potentially useful anti-cancer agents,” says principal investigator Dr. Tushar Patel, director of hepatology and a researcher with Ohio State’s Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute.

“For nearly two decades, cancer drug discovery has sought agents that block a single molecular target or pathway,” he says. “Our approach identifies agents that could potentially block tumor progression by striking multiple genes that are associated with a particular cancer-related behavior.”

New drugs for liver cancer are needed because the disease is widespread worldwide. The most common type of liver cancer, hepatocellular carcinoma, causes 630,000 deaths every year worldwide, and the incidence is rising in many countries, including the United States.

Only one drug is presently approved for treating advanced liver cancer, Patel says. He notes that several new agents are in development for the disease, but each affects just one or another of the many processes that are altered in liver cancer cells.

“We believe that targeting a certain type of tumor behavior might be helpful for liver cancer because many different biochemical pathways in tumor cells can be involved. Most targeted agents affect only one pathway, so a combination of drugs may be needed. Alternatively, new agents that hit multiple targets simultaneously could be used,” he says.

Patel and his colleagues began their study by identifying the gene changes present in liver cancers that had invaded neighboring blood vessels.

The researchers then looked for agents that could reverse these changes as a group. They did this using a database called the connectivity map, a collection of data sets that offers a way to compare gene changes caused by a disease with gene changes caused by different chemicals or drugs.

“We queried the gene changes present in invasive liver cancer cells against the connectivity map and looked for compounds that had an opposite effect on these changes,” Patel says. “If genes ‘A, B and C’ were increased in our tumor cells, we wanted to find an agent that decreased genes ‘A, B and C’,” he says.

Their search identified two compounds: Resveratol, a component of red wine that recently and coincidentally was shown by others to inhibit the ability of liver cancer cells to invade tissues and metastasize, and 17-allylamino-geldanamycin (17-AAG), which has shown anticancer activity in some solid tumors but has not been tested in liver cancer.

Last, the researchers used laboratory tests to verify that the two compounds actually did alter the invasive ability of liver cancer cells.

“This approach is exciting because it can be applied to any well-defined disease behavior,” Patel says. “It might also improve the approach to drug discovery and design if some agents were modified to select for a particular genomic profile rather than a single chemical target.

“Overall,” he says, “this could be a more relevant way of looking at cancer because we want to block certain disease changes and specific effects such as invasion, metastasis or chemotherapy resistance.”

Other Ohio State researchers involved in this study were Chiara Braconi, Erica Swenson, Lyudmyla Khrapenko and Nianyuan Huang.

Source : insciences.org

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