Internists reject clinical trial of controversial anti-dengue drug

Doctors from the Philippine College of Physicians (PCP) and the Philippine Society for Microbiology and Infectious Diseases (PSMID) have rejected the clinical trial done on the controversial ActRx TriAct, a drug claimed to be effective against dengue and malaria.

“We believe this trial was poorly designed and the data analysis was seriously flawed,” PCP president Anthony Leachon said Tuesday at a forum in Quezon City.

Leachon was referring to the clinical trial of ActRx TriAct done on 145 dengue patients of San Lazaro Hospital in 2013.

On-leave Health Secretary Enrique Ona  ordered in September the clinical trial of 2,000 units of ActRx TriAct for dengue treatment in six more government-run hospitals, after the supposed success of the clinical trial in San Lazaro Hospital in 2013.

Acting Health Secretary Janette Garin, however, ordered the expanded clinical trials to be suspended on November 14, to give way for a review on the matter.

Prior to this, clinical trial of ActRx TriAct for treatment of malaria was also done in selected areas in Palawan in 2012.

On December 1, through a statement, Garin ruled that the clinical trials in 2012 and 2013 should not have taken place.

Based on the record of the DOH close to 60,000 cases of dengue were recorded from January to September of this year with 242 deaths, mostly in children.

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Flawed analysis

Leachon, for his part, said that based on the Filipino physicians' own review, there was no extensive pre-clinical testing done before the clinical trial of the drug on humans was conducted.

He also pointed out that the analysis of the clinical trial saying that ActRx TriAct is a “promising” treatment for dengue was “flawed.”

“In this study, every subject of the clinical trial survived including those who did not receive the treatment,” he said.

There were a total of 290 dengue patients involved in the clinical trial in San Lazaro Hospital, of these half were administered with ActRx TriAct, while the other half were given the hospital's standard care for dengue.

“The only basis for expanding the use of this drug combination to several [Department of Health] hospitals was a study on 290 dengue patients in one medical center,” Dr. Mario Panaligan, member of the PCP Board of Regents and Vice President of PSMID, said.

“They claimed there were no deaths due to dengue among 145 patients who received this treatment in the clinical trial. However, they are not saying in public that those who did not get this treatment also survived, which does not provided extra benefit in preventing deaths,” he added.

This was echoed by Dr. Francisco Tranquilino, PCP Ethics Committee regent, who said it usually takes 10 to 15 years before a particular drug can be proven effective to cure a virus as the preclinical testing and the actual clinical testing are very elaborate processes.

“When you talk about preclinical testing, it should undergo laboratory testing, it should have undergone the review of its protocol by an accredited institutional review board and it should have been used in animal testing. And all these steps, we believe, are not present in this case,” Tranquilino said.

No FDA approval

Tranquilino expounded that while the artemisinin and its derivatives—artesunate and artemether—were already proven to have anti-malarial property, its safety and efficacy for use as treatment of another virus such as dengue has yet to be proven.

The ActRx TriAct is composed of three components, oral artesunate, arthemeter spray and oral berberine.

“Yung artemisinin and its derivatives [artesunate and artemether], yes, accepted yun for the treatment of malaria. Pero yung berberine is a herbal medication which has no indication. So, if a particular herbal medication is going to be used for a specific indication, such as, in this case, dengue, then it should go through the same process of approval as a new drug. Kailangang dumaan siya sa buong proseso like aproval from the FDA (Food and Drug Administration),” Tranquilino said.

He said the use of artesunate and artemether for a new indication aside from malaria, should have also undergone the approval of the FDA.

“Even for the artemisinin derivatives, ang indication niya is for malaria. It's not indicated for dengue, therefore if you're going to use it for another indication, it should apply for a new indication with FDA. It should go to a new process of approval as a new drug,” Tranquilino said.

Children as subjects

The group also slammed the people behind the clinical trial for including some children as subjects.

“The well-being of the human subject should take precedence over the interests of science and society... This study failed to prove that the triple drug combination works. Furthermore, it was unethical for the investigators to test drugs in children without first testing them in adults” the PCP and PSMID said in a joint paid statement that appeared in two major broadsheets on Monday.

In their statement, the group also called on the government to stop the expanded use of the treatment in more hospitals.

It also called for the publication of the full clinical trial report for public scrutiny, “or at least sharing it to all concerned parties.”

“Para sa amin, wala tayong sapat na pag-aaral ngayon upang magkaroon ng expanded clinical trial on dengue tulad ng gustong mangyari ng Department of Health. Ang pinagbasehan nila ay hindi sapat na basehan upang gawin ang clinical trial na ito sa mas maraming tao. Lalong lalo na kung kasama doon ang mga bata,” former PSMID president Dr. Rontgene Solante said during the forum, reiterating their earlier statement. —KBK/NB, GMA News