03 Jun Quintessence Biosciences moves ahead
Madison, Wis. – A few weeks ago, in this column, I wrote that folks at Madison-based Quintessence Biosciences eagerly anticipated the outcome of a Phase IIIb clinical trial that Alfacell Corp., a major East Coast competitor, would soon release on an anti-cancer therapeutic compound, Onconase. Quintessence’s lead drug candidate, QBI-139, is very similar to Onconase and has not yet been clinically tested.
The results of the Onconase trial were just released and Quintessence Chairman and CEO, Ralph Kauten said that he is “…disappointed that the results of the Onconase clinical trial were not an overwhelming success.”
Kauten shared with me a communication that Quintessence sent to its shareholders about the Alfacell trial. In it, they had this to say:
“Alfacell has released data indicating that their first-in-class drug, Onconase, failed to meet the primary endpoint in the Phase IIIb confirmatory trial in malignant mesothelioma. The trial compared the combination of Onconase plus doxorubicin to doxorubicin alone. The primary endpoint was an increase in overall patient survival. Alfacell’s initial analysis of the data showed no statistically significant improvement for evaluable patients receiving the combination of Onconase and doxorubicin.”
In other words, Alfacell tested the combination of Onconase plus the standard chemotherapy drug, doxorubicin, to doxorubicin alone in order to test whether Onconase would increase the survival of patients with mesothelioma, an extremely difficult-to-treat cancer that usually is associated with asbestos exposure. After the data were analyzed, there was no consistent difference in the two therapeutic regimens, which means that adding Onconase made no significant difference in the survival of the patients.
However, when the data were more closely examined, it appeared that a subset of patients who had failed the standard chemotherapy regimen for mesothelioma, showed a small but statistically discernable increase in survival when treated with Onconase. On this basis, Alfacell plans to submit an application to the FDA for using Onconase as a “second-line” therapy for mesothelioma patients who fail the standard chemotherapy. It is unclear how the FDA will respond to this parsing of the data. In the past, they have been averse to such sub-group analysis, but there are indications that this attitude may be changing, so Alfacell is forging ahead with the New Drug Approval process.
Cause for concern?
As I asked before, should there be cause for concern at Quintessence over these less than encouraging results from a competitor? As before, folks at Quintessence remain very committed to moving QBI-139 into clinical trials, probably sometime this summer. In their communique to shareholders, Quintessence went on to explain the following:
“Failing to meet the primary endpoints in the Alfacell Phase IIIb trial certainly makes approval of Onconase more challenging. However, Onconase still has significant potential to be approved as a second line treatment for malignant mesothelioma. While this change would mean a smaller market for the drug, our opinion has been and continues to be that any successful FDA approval of Onconase paves the way for general acceptance of RNases as cancer therapeutics.”
“Quintessence continues to make progress toward filing an IND and initiating a Phase I clinical trial for QBI-139. The majority of the data supporting the IND has been collected and analyzed and GMP manufacturing is underway. We are currently negotiating contracts with the clinical trial site as well as a contract monitoring group. We look forward to demonstrating the clinical benefit of QBI-139 in patients with cancer.”
The FDA’s response to Alfacell will be critical for the future of RNase-based therapies that Alfacell and Quintessence are developing. As I wrote in an earlier article, it is an unfortunate fact that if a drug is tested on the wrong disease and fails, it can be very difficult to resurrect its reputation in order to test it on another, more appropriate, disease. When a drug gets a bad reputation, it becomes much harder to garner enthusiasm from those who would fund the new study—investors and NIH grant reviewers.
Although, it may turn out that that testing Onconase on mesothelioma was a bad decision on the part of Alfacell, it was an interesting strategic decision that they made. Mesothelioma was chosen for the initial clinical trials because of its intractability to therapy, which allowed Onconase to be granted fast track status and orphan-drug designation by the FDA. This means that Alfacell was able to get Onconase into advanced clinical trials much sooner than it would have via conventional investigational drug approval procedures.
Mediocre therapeutic results against a cancer that no other therapy has shown much success against does not mean that RNase-based therapies will not be effective against other types of cancers. As I pointed out earlier, there is good reason to believe that Quintessence’s lead RNase therapy, QBI-139, is superior to Onconase.
For these reasons, Quintessence should and will continue to move forward with QBI-139 and focus on more common and easier to treat cancers than mesothelioma.
Recent columns by Steve Clark
• Steve Clark: Stem cell therapies are fast approaching
• Steve Clark: Stem cell frontier on display at Promega
• Steve Clark: Madison biotech company happy to ride the coattails of competitor
• Steve Clark: Understanding the science is key to predicting biotech success
• Steve Clark: Predicting success of early-stage biotechnology
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