In an article posted in this column a few weeks ago, it was reported that researchers at Madison-based Quintessence Bioscience were waiting for the results of a Phase IIIb clinical trial from Alfacell Corp., a significant East Coast competitor, on an anti-cancer therapeutic compound, Onconase. QBI-139, Quintessence's lead drug candidate, is very similar to Onconase but has not yet gone through clinical testing.
Upon the release of the Onconase trial results, Ralph Kauten, Quintessence Chairman and CEO commented that he was "disappointed that the Onconase clinical trial results were not reported to be overwhelmingly successful."
In a communication that Quintessence sent to its shareholders about the Alfacell trial, Kauten shared the following:
"Data has been released by Alfacell showing that their first-in-class drug, Onconase, did not meet the primary endpoint in the Phase IIIb confirmatory trial for malignant mesothelioma. The trial involved a comparison of a combination of Onconase plus doxorubicin versus doxorubicin by itself. The intended primary endpoint was an overall increase in patient survival. Initial analysis of Alfacell's data showed no statistically significant improvement for patients evaluated after taking the doxorubicin and Onconase combination."
Alfacell, in other words, tested whether treating mesothelioma patients with a combination of Onconase plus the standard chemotherapy drug, doxorubicin, would increase their survival at a statistically significant rate vs. those treated with doxorubicin alone. Mesothelioma is a very difficult cancer to treat and is generally related to asbestos exposure. Upon analysis of the data, there was no significant difference in survival rates when comparing the two therapeutic approaches which indicates that the patient survival rate was not favorably impacted by adding Onconase.
When the data were examined more closely, however, it became evident that a subset of patients failing the standard chemotherapy approach for treating mesothelioma, showed a small but statistically discernable increase in survival when they were treated using Onconase. It is based on the results of these data that Alfacell intends to submit an application to the FDA that would allow the use of Onconase as a "second-line" therapy for mesothelioma patients who do not respond to traditional chemotherapy. The FDA has not reacted favorably to this type of sub-group analysis of data in the past so it is unclear how they will respond to the application. Traditionally, they have not favored this type of analysis, but because there are emerging indications of a change in that attitude, Alfacell is continuing with the process for getting the new drug approved.
Is there reason to be concerned?
It was asked again if there should be any concern at Quintessence over these less than encouraging results from Alfacell. Despite the results, Quintessence remains committed to moving QBI-139 into clinical trials, most likely sometime this summer. In their communique to shareholders, Quintessence also explained the following:
"Getting Onconase approved is made more challenging because it failed to meet the primary endpoints in the Alfacell Phase IIIb trial. Onconase, however, still has major potential to get approval for use as a second line treatment therapy for malignant mesothelioma. This change would create a smaller market for the drug, but we continue to be of the opinion that the road to general acceptance of RNases as cancer therapeutics will be paved by any successful FDA approval of Onconase."
It was further reported that "Quintessence continues to progress toward filing an IND and starting a Phase I clinical trial for QBI-139. Most of the data that supports the IND has been collected and analyzed and GMP manufacturing is taking place. We are in contract negotiation with the clinical trial site and a contract monitoring group. We look forward to being able to demonstrate the clinical benefit of QBI-139 in patients who have been diagnosed with cancer."
The future of RNase-based therapies that Alfacell and Quintessence are developing hinges on the FDA's response to Alfacell. Unfortunately, if a drug is tested on the wrong disease and fails, it is difficult to try to test it on another, more appropriate, disease. If a drug gets a bad reputation, NIH grant reviewers and investors may not respond enthusiastically.
Testing Onconase on mesothelioma may turn out to be a bad decision on the part of Alfacell, but it was still an interesting strategic decision made by the company. Alfacell chose Mesothelioma for the initial clinical trials because of the stubbornness that Mesothelioma exhibits in response to traditional therapy. As a result, the FDA granted Onconase fast track status and orphan-drug designation and Onconase was able to get into advanced clinical trials much sooner that it would have otherwise.
The results that have been demonstrated by Onconase do not mean that RNase-based therapies will not work on other types of cancers and there is still reason to believe that Quintessence's lead RNase therapy, QBI-139 will be even better than Onconase.
No comments:
Post a Comment