While the Philippines recently announced a large national ivermectin trial targeting early-onset COVID-19, another commercial study seeks to accelerate sufficient safety and efficacy data in that Southeast Asian nation as well, as Merck recently kicked off a Phase 3 trial there testing the oral antiviral drug Molnupiravir, led by the Lung Center of the Philippines. Although Merck developed a version of ivermectin that’s been used to safely quell parasitic-born illness in many tropical areas for four decades, the company went on the offensive against its own product’s use as a therapy for the COVID-19 indication. So now the American pharmaceutical company is in a race against time and its own generic product to carve out market share as what has been a great American pharmaceutical company and Ridgeback Biotherapeutics LP came together to commercialize the drug initially discovered at Emory University. They compete potentially against Roche and Pfizer but also other drug companies developing oral antiviral treatments for COVID, such as ivermectin. According to local media, the Lung Center of the Philippines seeks participants for the study as it has only thus far enrolled a couple patients that have volunteered to take the drug twice a day for a minimum of five days. Meanwhile, the Philippines kicked off a major ivermectin trial targeting wide use for the vast majority of COVID-19 cases—those early-onset with mild to moderate symptoms.
COVID-19 in the Philippines
The Philippines is now in the midst of its second, much bigger wave of the COVID-19 pandemic. Its first wave started back in June of last year and through September but the daily case count never went above 7,000 cases in a day and by October 2020 through February 2021 the daily case count fluctuated between 1,000 and 2,000 cases. But by March, fueled by variants, a lack of any early-onset care and perhaps relaxing public health moves, the number of cases skyrocketed to 12,546 cases on April 6. By the end of May, the average daily count lowered to around 5,000 cases per day but have since gone back up to 7,205 by Sunday, June 6 according to data from Johns Hopkins University. Local press GMA reported active COVID-19 cases now number at 58.854. And according to data from Our World Data, only about 1.4% of the Philippines population have received a COVID-19 vaccine yet.
Growing Call for Ivermectin Use in LMICs
Much like in India, there’s been a call by a growing number of physicians here to use Ivermectin. TrialSite shared that while the wealthy secured access to remdesivir, the poor plead for ivermectin to the disdain of authorities. In many low-to middle-income countries (LMICs) combatting COVID-19, the now 58 studies pointing to positive data signals open an opportunity for a low-cost, possibly effective means for care.
However, unlike India, the Philippines is taking a more cautious and perhaps industry or Western academic-influenced route declared by the World Health Organization (WHO). The global health NGO declared that ivermectin should only be used in a clinical trial, despite all the studies, data and death from COVID-19.
In India, national-level health authorities by late April disregarded WHO and thus were including ivermectin in the national protocol treatments for COVID-19 (since June of 2020, some states had included for regional use), while in the Philippines, the regulatory body there allowed hospital access for compassionate use only although some communities pushed the boundaries initiating community ivermectin programs, but those were not well accepted by health authorities nationally. Hence, not surprisingly, just like in many other places, the growing chorus for ivermectin use raises controversy.
The tension led to a large Ivermectin-based trial, spurred on by the strongman president Rodrigo Duterte himself.
Enter Merck’s Branded Competitor
In the meantime, Merck is quietly inking deals around the globe to get Molnupiravir into clinical trials around the world. TrialSite reported that the pharmaceutical company approached and closed a deal with a handful of generic drug makers in India and now the Philippines is also on the list.
But unlike for more general early-onset care, in a bid to reduce disease progression, the use of Molnupiravir in this Phase 3 trial centers on those individuals 18 or up who are symptomatic, tested positive within the last five days, yet to be vaccinated, and face other risk factors and comorbidities such as diabetes, cancer and/or kidney and heart diseases.
Merck secured access to the drug via an alliance with Ridgeback Biotherapeutics LP last year. TrialSite reported that Merck was also paid $356 million by the U.S. government in association with the development of a company it announced it would acquire for $425 million in November 2020 (OncoImmune). But interestingly, they quickly stopped any development of that biotech’s drug called MK-7110 yet it’s not clear if the public funding was applicable to the Ridgeback drug (Molnupiravir). Importantly, the Ridgeback investigational product (now MK-7110) was at the center of controversy involving a federal whistleblower and what amounts to claims of scientific crony capitalism in the last POTUS administration.
At the same time, Merck finally came forward with a statement on Ivermectin: it bashed the drug’s considered use for COVID-19 challenging not only the over 50 studies at the time already evidencing some data for efficacy but surprisingly also its safety. As Merck is fully aware of the dosage parameters within these many studies, the drug is safe and has been in use for four decades. Merck has successfully given away over a billion doses to fight tropical parasites in Africa, for example.
The Global Molnupiravir Study
This Phase 2 and 3 study (NCT04575584), now conducted at at least 89, if not more, trial sites around the globe, including the Philippines Lung Center, aims to evaluate the safety, tolerability and efficacy of the study drug (Molnupiravir or “MK-4482”) compared to placebo. Merck’s foremost hypothesis centers on the assumption that the drug will be superior to placebo as assessed by the rate of sustained recovery through 29 days.
According to the trial disclosure, the New Jersey-based company is enrolling 304 participants and targets a total of three primary endpoints including the one already mentioned (Time-to-sustained recovery) as well as percentage of participants with an adverse event up to seven months (safety) and percentage of participants who discontinued the study due to adverse events. Secondary endpoints can be reviewed here.
As mentioned in a previous TrialSite piece, Merck’s in a race not only against its own generic competition (Ivermectin) but also against a formidable competitor in Roche as well as Pfizer, which is a little behind with an early stage oral available investigational product. This particular study commenced during October 2020 and runs through this summer until August 2021.
Health Undersecretary Maria Rosario Vergeire shared recently on the study, “That’s part of what we have endorsed. We are open to trials and to trying these interventions to help treat our COVID-19 patients” as reported in local news GMA. While Dr. Leo Olarte, former President of the Philippine Medical Association, shared his enthusiasm for welcoming the study if it proves safe and effective, looking at it as a “cure” while the vaccine is more used for prevention. But are they also using it as a prophylaxis in the Philippines? According to GMA News, Jon Viktor Cabuenas shared, “if this oral medicine can be both preventive and curative, double whammy, it would be better.” Responding to TrialSite Mr. Cabuenas clarified that the study is only for treatment.
The Lung Center of the Philippines is a government-run tertiary hospital specializing in the cure and prevention of lung and other chest diseases, located in Quezon City. Receiving public funding, the hospital was built on land donated by the National Housing Authority in the Philippines. With a hospital bed capacity of 210, the center was first launched back in 1981 by then President Ferdinand Marcos as a non-profit, non-stock corporation via executive order. Marcos, of course, was deposed when the center was placed under the administration of the Ministry of Health (present-day Department of Health) by President Corazon Aquino in 1986 under another executive order. The center exists to provide health care that specifically targets lung and pulmonary care.
The Lung Center’s Institutional Ethics Review Board oversees the ethics of research conducted at the hospital. This local ethics committee executive director is Vincent M. Balanag, Jr. Research and Development here is headed up by Sullian Sy Naval, MD.
The other Philippines-based trial site for this study is the University of Philippines, Philippine General Hospital in Manila.