Ona in trouble over use of malaria-dengue drug

By: Christian V. Esguerra - 10 years ago

Health Secretary Enrique Ona. INQUIRER FILE PHOTO / NIÑO JESUS ORBETA

MANILA, Philippines–Health Secretary Enrique Ona, who is on leave, is under scrutiny for authorizing the use of a supposed “breakthrough” drug for the treatment of malaria and dengue.

Documents obtained by the Inquirer showed acting Health Secretary Janette Garin has begun looking into “ActRx TriAct,” a two-day regimen described on the website of a private firm that developed it as a “new breakthrough treatment for dengue.”

Administered by spraying the contents under a patient’s tongue, the herbal-based treatment combines artemether and artesunate, derivatives used to treat malaria, with berberine, a plant compound used in traditional Chinese medicine.

Order suspended

Garin earlier suspended Ona’s Sept. 24 order allowing San Lazaro Hospital and four other government hospitals to administer the treatment.

Other state-run hospitals that Ona reportedly authorized to administer ActRx TriAct were East Avenue Medical Center, Dr. Jose Rodriguez Memorial Medical Center, Amang Rodriguez Memorial Medical Center, Quirino Memorial Medical Center and Jose B. Lingad Memorial Regional Hospital.

WHO warning

A Nov. 21 letter by Dr. Julie Hall, the World Health Organization (WHO) representative to the Philippines, warned the Department of Health (DOH) against using “Artemisinin combination treatment” (ACT)—the “mainstay of treatment for falciparium malaria saving thousands of lives each year”—as a form of “monotherapy.”

“The loss of ACT as an effective treatment for malaria would therefore have a devastating effect impact on the health of many people in malaria-endemic countries and threaten the recent progress on malaria control,” Hall wrote Garin, who had sought “technical assistance and opinion” in a Nov. 19 letter.

Development of resistance

“The use of oral artemisinin monotherapy has been shown in a number of countries to have contributed significantly to the development of resistance of falciparum malaria parasites to all forms of artemisinin.”

Ona is on a monthlong “leave of absence” while preparing his explanation for authorizing the purchase in 2012 of Pneumococcal Conjugate Vaccine 10 (PCV 10) instead of the supposedly more cost-efficient PCV 13. His leave will expire on Nov. 28.

In the meantime, Garin has moved a number of health officials identified with Ona to their original posts. Among them was Director Eric Tayag of the National Epidemiology Center who had been “designated” assistant secretary under Ona.

Hall’s letter noted that a “similar regimen was advertised by the manufacturer as a potential treatment for malaria in the Philippines.”

Coendemic

“It should be noted that the WHO does not recommend the treatment of dengue with single or combined derivatives of artemisinin,” she wrote.

“As in the Philippines, in some areas, malaria and dengue are coendemic, if the artemisinin regimen suggested in the DO [department order] were to be used in those areas for dengue, resistance to malaria could emerge,” Hall said.

Dengue, a mosquito-borne disease like malaria, has claimed the lives of at least 1,680 people in more than 416,000 cases reported in the country over the past three years.

Last year, the Food and Drug Administration (FDA) sent a team to Rizal, Palawan province, to investigate a “reported death resulting from a malaria clinical trial.”

Also under scrutiny was Preferred & Proven Therapies Inc., described as the exclusive Philippine distributor of ActRx TriAct, and a supposed antimalaria drug that combined “artemether + artesunate + berberine” with primaquinine.

Firm based in Clark

An Inquirer report on ActRx TriAct, dated Oct. 20, described Preferred & Proven Therapies Inc. as a firm operating at the Clark Special Economic Zone in Pampanga province.

The report said the firm discovered the treatment after five years of testing in collaboration with ActRx Foundation, an international humanitarian and medical research group based in North Palm Beach, Florida, in the United States.

While the death of a 4-year-old girl “seems to be not related to the drug,” said the FDA report, medical investigators wanted to stop the clinical trial “as there was no FDA approval of the protocol.”

The team recommended a “dialogue with [Secretary] Ona to explain this trial.” It also called for an investigation of the “ongoing trial on dengue using the same test drug at San Lazaro Hospital.”

On July 3, 2013, then acting FDA Director Kenneth Hartigan-Go ordered the termination of the clinical trial and “any similar trial involving the same drug.” He said “data gathered from these trials are invalidated for drug registration purposes.”

Ona order

But on Sept. 24 the following year, Ona issued DO No. 2014-0161, integrating the ActRx TriAct treatment in the “standard of care in the management of dengue incidents in the Philippines.”

Less than two months later, Garin suspended the order and gave the FDA and the Philippine Institute of Traditional and Alternative Health Care (PITAHC) 15 days to recommend “whether the program must continue.”

In a June 10 letter to the FDA, the Philippine Council for Health Research and Development said: “The combination of artemether and artesunate in a single-drug formulation for the treatment of dengue was not scientifically justified since these compounds are proven therapies for malaria.”

“We should likewise be cautious in using these compounds for indications other than malaria since it might induce resistance thereby jeopardizing our line of defense against malaria,” wrote Dr. Jaime Montoya, the council’s executive director.

In his now suspended order, Ona said that “in line with its mandate to protect public health and guarantee public access to essential drugs, the DOH—in collaboration with the PITAHC and the Department of Science and Technology (DOST)—shall make available and integrate the ActRx TriAct treatment into the national health-care program for dengue.”

He also called for the inclusion of ActRx TriAct in the Philippine National Drug Formulary, “subject to the review by the Formulary Executive Council in accordance with existing rules and regulations.”

Remarkable success

Ona said that “on March 15, Preferred & Proven Therapies Inc., ActRx Foundation and ActRx Operational Group, together with the PITAHC and San Lazaro Hospital for Infectious Diseases medical research team, presented a report showing the remarkable success of the clinical trials conducted at San Lazaro Hospital on ActRx TriAct.”

“After its independent study, the Philippine Council for Health Research and Development of the DOST likewise noted the remarkable results of ActRx TriAct and fully endorsed the implementation of a national program using the said treatment,” he said.

Ona quoted Montoya as saying that a “review of the [ActRx TriAct] protocol shows that it is scientifically valid and sound to be carried out in hospitals.”

The health secretary said that “currently, there is no specific treatment for dengue.”

“The standard of care administered to patients afflicted with dengue involves only maintenance of the patient’s body fluid volume and relief of symptoms,” he said.

Ona noted that dengue in the country had in recent years become an epidemic.

In 2012, there were 187,031 cases of dengue with 921 deaths, as reported by the National Epidemiology Center of the DOH. In 2013, the DOH recorded 204,906 dengue cases and 660 deaths.

This year, some “24,900 cases have resulted in [at least] 100 deaths, or a ratio of one fatality for every 249 cases,” Ona said.