Today Alfacell, the manufacturer of ONCONASE, announced it will begin distribution of the mesothelioma drug in Israel. The company will partner with Megapharm, Ltd., a leading pharmaceutical company in Israel. ONCONASE recently completed an international confirmatory Phase IIIb clinical trial for unresectable malignant mesothelioma.

The news comes just a day after Haaretz.com, a leading news outlet in Israel, noted that asbestos-related cancer is 10 times more prevalent in Nahariya, a city of approximately 50,000 located in the North District of Israel on the Mediterranean sea, just south of the Lebanese border at Rosh HaNikra, than it is in the rest of the country. The report is based on data submitted by the chief doctor of the Health Ministry’s Acre District.

The medical report was presented to the Knesset Internal Affairs Committee, which is currently calling for greater action from Nahariya’s government to address the problem. The story quotes Tamar Bar On, head of the Environment Ministry’s Asbestos Department, as saying that “between 70 to 150 thousand cubic meters of asbestos [can] be found scattered across the Western Galilee, mainly in private yards.”

Committee MK Yossi Beilin (Meretz) has been selected by the committee to chair a panel dedicated to addressing the asbestos problem in Nahariya.

Alfacell will manufacture and supply ONCONASE to Megapharm, while Megapharm will be responsible for all activities and costs related to regulatory filings and commercial activities in a defined marketing territory, according to an Alfacell press release.

ONCONASE is a first-in-class therapeutic product candidate based on Alfacell’s proprietary ribonuclease (RNase) technology. A natural protein isolated from the leopard frog, ONCONASE has been shown in the laboratory and clinic to target cancer cells while sparing normal cells. ONCONASE triggers apoptosis, the natural death of cells, via multiple molecular mechanisms of action.

ONCONASE has been granted fast track status and orphan-drug designation for the treatment of malignant mesothelioma by the FDA. Additionally, ONCONASE has been granted orphan-drug designation in the European Union and Australia.

On April 21 I reported that a Madison, Wisconsin-based biotechnology firm, Quintessence Bioscience, was moving forward on a drug similar to Alfacel’s Onconase, to treat mesothelioma. The report, from Steve Clark for WTN (Wisconsin Technology Network) News, noted that the company’s QBI-139 is very similar to Onconase, but has not been clinically tested yet.

Of course, on Monday this week, it was announced and reported here that Onconase had failed the primary objective of its late-stage trial. This news was particularly disappointing since the drug already has orphan drug status in the U.S., Europe and Australia due to the very high hopes for its success. Despite failing in its primary objective, however, testing did show that the drug is effective in a secondary effect, helping to prolong the life of those treated after standard chemotherapy has failed.

The report of Onconase’s initial failure prompted WTN’s Clark to revisit Quintessence to find out if the Onconase failure would derail the development of their QBI-139. In his new report, Clarks says he found researchers undaunted and pressing forward. He says they hope to move the drug into clinical trials sometime this summer, and they believe the success of Onconase’s secondary role and hopeful FDA approval in that area will help pave the way for general acceptance of RNase cancer therapies.

In his earlier report, Clark pointed out that QBI-139 has several differences from Onconase in the way it is produced, which he believes will make it inherently more effective than Onconase.

He points out that mesothelioma is a particularly difficult cancer to treat, and wonders if the selection of mesothelioma as a research track by Alfacell was made to help fast-track the development of the drug. Perhaps, he wonders, the drug might be more effective on “more common and easier to treat cancers than mesothelioma.”

Alfacell Corp., a biotechnology company that manufactures Onconase, released a disappointing report Wednesday regaring its Onconase product, which was hoped to be a significant treatment for mesothelioma. The drug already has orphan-drug status for the treatment of malignant mesothelioma in the U.S., Europe and Australia.

Results of the company’s late-stage trial of the drug showed that Onconase did not achieve significantly higher survival rates among patients with unresectable malignant mesothelioma when given in combination with doxorubicin, another cancer chemotherapy drug.

According to a report on Pharmaceutical Online, the preliminary results are based on 320 evaluable events that occurred in the clinical trial out of a total of 428 patients randomized. The analysis of the data did not show a statistically significant improvement for evaluable patients receiving Onconase plus doxorubicin. The median survival time (MST) for evaluable patients who received Onconase plus doxorubicin was 11.1 months as compared to 10.7 months for patients who received doxorubicin as a single agent.

However, there is a silver lining to the study. Pharmaceutical Online reports those patients who failed a previous chemotherapy regimen who received Onconase plus doxorubicin experienced a MST of 10.5 months compared with 8.7 months for those patients who received doxorubicin, which is considered a statistically significant result.

Reuters reports as a result of this secondary finding, Alfacell will now submit a marketing application to the Food and Drug Administration for use of the drug on those patients, with hopes to have it approved by the end of the year.

I recently posted about the progress of a new drug to treat mesothelioma, called ONCONASE, which has completed Phase IIIb clinical trials and is being fast-tracked for approval in the U.S. ONCONASE already has orphan-drug status in the EU and Australia.

This week, I found a story that provides even more hope. It seems a Madison, Wisconsin-based biotech firm, Quintessence Bioscience, also has a promising mesothelioma drug in the works that operates along the same lines as ONCONASE, tagged QBI-139. The Quintessence drug is not yet in clinical trials.

Both drugs target RNA in cancer cells. They are therapeutic ribonucleases (RNases), which WTN News (Wisconsin Technology News) writer Steve Clark describes as “ubiquitous enzymes that destroy RNA.” He explains that researchers including the University of Wisconsin-Madison’s Ronald Raines, “discovered that RNases from non-human species sometimes are not regulated inside human cells and can cause cell death. Surprisingly, cancer cells are much more susceptible than normal cells to foreign RNases.”

The ONCONASE product is made from purified frog eggs. The Quintessence drug is 95 percent human, but still kills human cancer cells, Clark reports. Both drugs can kill a wide range of different human cancer types, he says, so its application has broad potential. The ONCONASE clinical trial data is from patients with malignant mesothelioma.

Clark reports that Quintessence is optimistic about its QBI-139 surpassing the positive results of ONCONASE. He says that frog-derived ONCONASE has been shown to cause allergic reactions in some patients, which would be mitigated in the 95 percent human-gene QBI-139. Additionally, he reports QBI-139 is less toxic than ONCONASE, which will allow it to be better tolerated by some patients in larger doses.

Currently, Clark reports, QBI-139 is being produced for use in a Phase I clinical trial, which is set to begin this summer and end sometime in 2009. It is anticipated that the trial will be held at the University of Wisconsin Carbone Cancer Center.

Read the full article at WTN News.

Steve Clark, Ph.D., is a former professor and medical researcher at the University of Wisconsin School of Medicine and Public Health, and is currently a freelance writer and consultant on biotechnology issues.

SOMERSET, N.J., April 2, 2008 - PRNewswire - Alfacell Corporation today announced that it has confirmed that 316 evaluable events (patient deaths) have occured in the confirmatory Phase IIIb clinical trial of its lead compound, ONCONASE (ranpirnase), for the treatment of patients with unresectable malignant mesothelioma (UMM).

In accordance with the statistical plan for the trial, the company has begun the process necessary to conduct the formal statistical analyses required to complete the final sections of the ONCONASE rolling New Drug Application (NDA).

The trial was designed to show a statistically significant improvement in overall survival for UMM patients who were treated with a combination of ONCONASE and doxorubicin as compared to UMM patients who were treated with doxorubicin as a single agent. Enrollment in the ONCONASE Phase IIIb clinical trial closed on Sept. 30, 2007. A total of 428 patients were enrolled in the trial.

Alfacell has licensed the U.S. commercial rights for ONCONASE to Strativa, the branded product division of Par Pharmaceuticals, Inc. Strategic marketing and distribution agreements for ONCONASE have been secured with BL&H Co. Ltd. for Korea, Taiwan and Hong Kong, USP Pharma Spolka Z.O.O., an affiliate of US Pharmacia, for Eastern Europe, and GENESIS Pharma, S.A. for Southeastern Europe.

ONCONASE has been granted fast track status and orphan-drug designation for the treatment of malignant mesothelioma by the U.S. Food and Drug Administration (FDA). Additionally, ONCONASE has been granted orphan-drug designation in the European Union and Australia.