By Kemo Cham
Many new grounds were broken during the 2014 Ebola outbreak, notably the use of untested vaccines and drugs.
The reasoning was that given the severity of the epidemic, the affected countries – Guinea, Liberia and Sierra Leone – had nothing to lose by using these candidate drugs and vaccines.
But at the backdrop of this debate was a less publicized one on the possibility of using existing drugs which had been approved for other diseases but which some in the scientific community say could well be good against Ebola. Three such drug classes - Statins, Angiotensin Receptor Blockers (ARBs), and Estrogen Receptor Modulators (ERMs) – are at the center of the debate in Sierra Leone.
Introduced as a combination therapy by the Netherlands-based Concordia Medical, the medications were originally targeted at acute Ebola patients but doctors in Sierra Leone have used them on survivors with encouraging success.
After over a year, the medication billed as the answer to the sufferings of over 4000 Sierra Leoneans who survived the Ebola virus disease was cleared for distribution last month by the government.
Brief trial
Since October 2014, Concordia had been trying to convince the government to consider the therapy for acute Ebola patients. But the company said reluctant health ministry officials shunned them and failed to readily grasp the rationale of their use.
After some maneuvering, however, which included engaging highly placed political figures with links to State House, the Concordia therapy went through a brief trial at the 34 Military Hospital in Wilberforce, between November and December 2014.
Willem Tijssen, Africa Representative of Concordia Medical, told Politico that feedback from doctors showed it proved effective. He said out of 300 people enrolled in the trial, all but two recovered within 15 days.
The two, one of whom was Dr. Aiah Solomon Konoyeima, the 10th of 11 Sierra Leonean doctors who succumbed to the virus, were enrolled late, making it hard to save their already failing organs, he said.
Dr Montgomery Harding, Orthopedic and Trauma Surgeon at the Davidson Nicul Hospital in Freetown, reviewed the literature of the therapy. The National Ebola Response Center (NERC) needed his expert recommendation for final decision on the use of the drugs. He said he submitted it as far back as October 2014. But despite finding a “strong scientific basis”, he was surprised that both NERC and MoHS officials “dragged their feet.”
Harding said authorities at the Ministry of Health and Sanitation (MoHS) appeared hostile to the medication and he suspected this was due to failure to examine the evidence objectively and scientifically.
Harding and other doctors in support of the Concordia supplement say it is not new, having been in the market for at least half a century and had been proven scientifically as viable treatment options, wondering therefore why so many patients were denied the medication for so long. The approach should always be scientific with no place for spontaneous hostility, he said.
For the case of Ebola, this therapy is being promoted on the basis of strengthening immune response, rather than attacking the virus itself.
SERMs, for instance, which are approved by the United States Food and Drug Administration (FDA), were identified among 53 existing drugs by a study conducted by the Icahn School of Medicine and the National Institutes of Health in the US in December 2014 as potentially effective in preventing the Ebola virus from entering human cells.
Statins, ARBs and a host of the other widely used, cheap medicines were recently the subject of a debate among 80 international researchers regarding their potential in treating Ebola.
The three combinations were identified for the following reason, as explained by Willem. The ARBs, he said, work in such a way that they can prevent a virus from penetrating the cells. But if the cells have already been penetrated, the SERMs act to prevent multiplication of the virus already present in the blood. And the Statins prevent the protein needed to transport the virus if they have already multiplied.
Willem is neither a scientist nor a medical doctor.
But his Sierra Leonean counterpart, Harding, a scientist and medic, agrees, saying the goal of the therapy is to prevent the survival and multiplication of the virus.
The combined action of the three medications prevents the virus from functioning and to eventually self-destruct, he said.
Paradigm shift
Treatment for Ebola is through supportive care, and because patients suffer massive fluid losses the focus is restoration of these fluids. Statins and ARBs are known for maintaining or restoring endothelial barrier integrity, the absence of which causes massive loss of fluid.
According to an April 28, 2015 publication in the International Journal of Infectious Diseases, approximately 100 Ebola patients were treated with atorvastatin and irbesartan, two drug classes of Statins, and all but two inadequately treated patients survived.
“Unlike other treatments that target the Ebola virus itself, this ‘bottom up’ approach to treatment represents a paradigm shift by targeting the host response to infection,” argues David Fedson, former professor of Medicine at the University of Virginia School of Medicine, a fervent supporter of generic therapy for Ebola.
Although it was initially targeted at acute Ebola sufferers, Harding said the therapy is even likely to be more effective on survivors given the low viral load in their system. In his trial on survivors, he used two different approaches – first a single drug – Statins - on two patients, and then a combination of two of the drugs - ERMs and Statins on eight patients.
“Between five and 10 days all symptoms [of survivors] disappeared,” he explained.
In all, the medication has been trialed on some 30 survivors in Freetown, according to Concordia and the Sierra Leone Association of Ebola Survivors (SLAES). Some of the survivors who spoke to Politico gave favorable review of its effect.
Philip Koroma was the first survivor to take the medication. He introduced his colleagues at the SLAES to it.
Koroma told Politico that all his pains “disappeared” after taking the pills. Even his experience of erectile dysfunction, a common symptom among survivors of the Ebola disease, disappeared.
“Survivors are anxiously looking forward to take the medicines and they have been constantly asking us about it,” said Dady Hassan Kamara, Public Relations Officer of SLAES, who is also a beneficiary.
Detailed data
But doctors opposed to the Concordia supplement say a lack of detailed data means they can`t say for sure its effectiveness.
Dr Peter George, head of the Maforki Ebola Treatment Center in the Port Loko district, treated 10 acute Ebola patients with the medication. But despite the “good outcome”, he said he couldn’t say for sure the drugs cured Ebola as there was no scientific method and analysis to show this.
“The center generally had good outcome of treatment and this was not isolated to only those that had the Concordia supplementary medications,” he said in an emailed response to Politico.
“At that time whatsoever drug that was said to produce good results in the care for EVD patients was received; just like the Nano Silver that was also sourced from somewhere else. In this respect, there was no basis to associate outcome with the Concordia therapy,” he said.
Dr George added that he could not work against ethics of research and therefore ruled out taking part in any further trial.
Those who know about Dr. George`s initial position on the therapy believe he was “most probably intimidated” into changing his opinion.
Harding is planning a larger and “more comprehensive” trial with the medication.
“A properly controlled clinical trial should be done on all survivors, so that we can have a clear scientific approach,” he said, adding that a proposal for this had already been sent to the NERC.
According to sources, the required dosage will cost around US$300, 000 for the over 4000 survivors in Sierra Leone.
When Willem and co realized reluctance on the part of health officials last year to consider the drugs for trial and sought support from State House, on August 6 President Ernest Bai Koroma gave his approval, followed by Health Minister Dr Abu Bakarr Fofanah.
But even with that approval from the top, effort to have the medication ordered was delayed and those who are in the know blamed the MoHS officials.
“That is a major issue in this part of the world. We [Western world] always want to have things speed up because you want to help people,” said Willem who believes that if the medication had been acknowledged on time many lives could have been saved.
The MoHS officials were not available for comment on the matter.
(C) Politico 16/11/15
