Alfacell said it also is implementing a plan to reduce or eliminate non-essential personnel and development costs so that it can focus entirely on efforts to complete a rolling New Drug Application (NDA) for ONCONASE, its mesothelioma drug. As we reported last week, Alfacell has a pre-NDA meeting with the U.S. Food & Drug Administration at the end of January 2009 to move ONCONASE forward.

ONCONASE is for patients with unresectable malignant mesothelioma, targeting those who have failed one prior chemotherapy regimen. Results of the drug’s Phase IIIb clinical trial showed “significant improvement” for patients in this category treated with ONCONASE.

According to Alfacell information, ONCONASE works by triggering apoptosis, the natural death of cells, through use of the company’s proprietary ribonuclease (RNase) technology.

An Associated Press report says Kenyon will replace Par Pharmaceutical’s CFO Veronica Lubatkin, whose departure will be effective March 6, 2009. Par is a generic-drug manufacturer.

SOURCE: myMeso › Alfacell’s Kenyon announces resignation

The company reports a drop in cash and cash equivalents to $2 million, down from $4.7 million in July 2008. However, the company received $1.1 million from the sale of state tax loss carryforwards in New Jersey in December 2008, and says its cash reserves “are sufficient to support its activites into the fourth quarter of fiscal year 2009,” according to the report.

Following the Phase IIIb clinical trial, it was determined ONCONASE results in a statistically significant improvement in survival for patients with unresectable malignant mesothelioma who have failed one prior chemotherapy regimen. This represents a currently unmet medical need, and Alfacell will meet with the Food and Drug Administration in January 2009 to discuss details of its planned New Drug Application submission.

According to information provided by Alfacell, “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.”

SOURCE: myMeso › Alfacell moving forward with ONCONASE while feeling financial pinch

The report is the result of collaborative research conducted at the Brander Cancer Research Institute and the Department of Pathology at New York Medical College, in conjunction with the drug manufacturer, Alfacell.

The new study provides further evidence of the impact ONCONASE has on the RNAi mechanism, said Alfacell CEO Kuslima Shogen in a company news release. Shogen said it also provides evidence as to why ONCONASE helps sensitize cells to other antitumor agents.

According to the release, “The study demonstrated that silencing the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene (an abundant and ubiquitously expressed housekeeping gene) in human lung adenocarcinoma A549 cells by siRNA was effectively prevented by ONCONASE. While transfection of cells with GAPDH siRNA reduced expression of this protein by nearly 70 percent, the expression was restored in the cells exposed to ONCONASE for 48 or 72 hours. The data thus provide evidence that one of the targets of ONCONASE (ranpirnase) is siRNA.”

Results of ONCONASE Phase III clinical trials, “demonstrate significant efficacy in patients with malignant mesothelioma that failed prior chemotherapy,” according to Alfacell information. The drug utilizes a proprietary ribonuclease (RNase) technology that targets cancer cells while sparing normal cells.

SOURCE: myMeso › Report supports ONCONASE as effective treatment for mesothelioma, tumors

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.

SOURCE: myMeso › ONCONASE expands to Israel as meso concerns there grow

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.”

SOURCE: myMeso › Quintessence continues with mesothelioma drug

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.

SOURCE: myMeso › Onconase fails in primary late-stage trial

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.

SOURCE: myMeso › ONCONASE on fast track for Meso treatment