It was an obvious failure of a drug trial, but the drugmaker said it was not because of the drug but patients' receiving of other medications that caused data distortion. About 35 percent of the participants used other medicines during the study, the company claimed.
This is what SillaJen said first about why it suspended the phase-3 trial on Pexa-Vec, an oncolytic viral drug. It admitted that the company failed to take this “bias” into account when French, Korean, and Chinese researchers made the clinical design. The company almost advertised that it was too incompetent to design and control a clinical trial.
In such a situation, SillaJen must have wanted to emphasize the potential of Pexa-Vec. It held an urgent news conference over the weekend to support anticipation for the investigational drug, hoping that its nosediving stock prices could rebound.
Asked by a reporter about detailed results of the suspended phase-3 test, SillaJen said, “We have not analyzed anything because it has been only one day since we received the data.”
However, in just one day, the company disclosed “factors that may have affected the trial failure, not the ones caused by the effect of Pexa-Vec.”
“Administering other drugs seems to have significantly affected the entire phase-3 trial. We cautiously predict that the major cause of the failure is not related to the effect of Pexa-Vec,” SillaJen said.
The basics of announcing a clinical result are to release numbers related to the primary and secondary endpoint and analysis on the data. Evaluation indices for the primary endpoint of the PHOCUS study on Pexa-Vec included overall survival (OS), and those for the secondary, progression-free survival (PFS) and overall response rate (ORR). So, when the company announced the clinical results, it should have presented the underlying indices first, even if other medications distorted clinical data.
If the company was still analyzing the data, it should have been more careful in releasing announcements.
Transgene, a European partner for SillaJen, also announced the Data Monitoring Committee’s recommendation to suspend the phase-3 trial on Pexa-Vec on Friday.
“SillaJen has informed Transgene of the IDMC’s recommendation to stop enrollment in the study, as the study is unlikely to meet its primary objective by the time of the final analysis. SillaJen has not reported safety concerns,” Transgene said in a statement, adding that it would provide an update in an upcoming conference call.
A scrap of the study must have been a shock to Transgene, but the company did not mention anything about other medicines. Transgene was not eager to emphasize Pexa-Vec’s potential value, either.
At a news conference on Monday, SillaJen again focused only on talking about the “effectiveness of Pexa-Vec.” It introduced three or four good examples, including an aged patient with multiple metastases to the lung after renal cancer surgery who achieved complete remission after the combination therapy of Pexa-Vec and an immune checkpoint inhibitor.
The company, of course, could pin hopes on a couple of cases. However, it is dangerous to conclude that several such cases could confirm the efficacy of Pexa-Vec.
An immune checkpoint inhibitor has a broad spectrum of response rate. It could help some patients completely cure. However, it also could rarely work on others. The several patients introduced by SillaJen could have benefitted from Pexa-Vec, but the immune checkpoint inhibitor could have worked better for them. Considering the clinical data on immune checkpoint inhibitors to date, it is more likely that the patients benefitted from the immune checkpoint inhibitor.
If the company wanted to highlight the effectiveness of Pexa-Vec, it should have presented other evidence such as PD-L1 expression.
Especially when the company failed the trial, it should have been cautious about providing any rosy picture for investors. However, what it did was precisely the opposite. The company is again trying to woo investors by telling them that it could prove Pexa-Vec’s value in the next trial. Shareholders will fall into an endless trap where the anticipation for the experimental drug moves from the failed liver cancer trial to another for renal cancer, another for colon cancer, and still another for breast cancer. In actuality, the company did not even manage to complete the phase-3 trial.
No one knows if SillaJen will prove Pexa-Vec’s efficacy in the next study. However, based on the only facts available on the table, industry watchers bet on the negative scenario. The facts include the failure of the global phase-3 trial in liver cancer, the failure of the protocol control in the study, and the too-small number of good cases – three or four only -- in other types of cancer.
In the news conference, SillaJen’s Chief Medical Officer Kwon Hyuk-chan repeatedly emphasized that “Pexa-Vec was not a fake drug made of water.” It is not important whether Pexa-Vec is made of water or not. What’s important is whether it could obtain approval as a “treatment.”
SillaJen will have to prove whether it obtained several good cases just by luck or the drug worked so that it will be potent on many other patients, too.
If the company still have no other evidence, but empty words such as “Pexa-Vec is not a fake drug” even when hundreds of patients participated in the trial, the company should be ashamed of itself.
If SillaJen is confident about Pexa-Vec, prove it with a clinical trial and shout out loud, “Pexa-Vec is an excellent treatment.”
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