Purchasing the Wrong Drug for COVID

 "...You have to purchase the right drug, not the wrong drug [to be prepared with effective COVID-19 treatments]."

"If they haven't spent the money, hold off for the good drug. If they have, try to get a refund."

Dr.Jeffrey Glenn, virologist, Stanford University

Image of antiviral medication Molnupiravir. (Merck & Co. via AP)

 

Good advice, but advice Canada, reacting rashly, failed to observe. Instead, the government of Canada proceeded directly, even before Health Canada had sufficient background investigative data through completed pharmaceutical research, to decide whether to give the Merck drug Molnupiravir, clearance for use in Canada as an approved drug. Health Canada is in the process of evaluating Molnupiravir under a "rolling submission" that began in August. Full data from its phase 3 trial has not yet been transmitted.

Despite which, the Canadian government has taken it on good (naive) faith that the drug will live up to its manufacturer-touted expectations, absent affirmatively positive results. So it has committed itself by buying 500,000 courses of the yet-to-be-approved medicine at a cost of approximately $450 million, with an option to purchase yet another half million courses with the pills to be manufactured in Ontario.

Now, a new analysis by British scientists argue Merck's phase 3 trial's main finding boasts a 30 percent reduction in hospitalization among patients taking the pills in early COVID onset. That modest reduction is held not to be statistically significant, particularly since the second half of the trial saw superior outcomes for patients receiving a placebo in place of the drug. Moreover, according to the U.K. paper, patient-level databases that could be investigated for "the risk of bias or medical fraud" have not been made available.

"Spending money on a drug that at best is only minorly effective is inappropriate use of Canadian taxpayers' money", observed Ed Mills, part time McMaster University professor, heading one of the world's largest COVID treatment studies. And several days previously the French health minister, stating study results "weren't good" revealed that the French government had cancelled its order for the drug.

In its defence Merck Canada spoke of its MOVE-OUT trial recently published in the New England Journal of Medicine, where it found the drug to have significantly reduced risk of hospitalization and death for high-risk, unvaccinated patients with mild to moderate COVID symptoms. Merck had licensed several generic manufacturers in India to produce the drug for lower-income countries.

Two of the companies -- Aurobindo and MSN -- conducted trials on moderately affected patients but stopped their trials when they indicated no benefit from the drug. A third Indian trial of over 1,200 mild patients reported that Molnupiravir did reduce hospitalizations with other benefits, in as-yet unpublished results.

Whether Canada could under its contract with Merck cancel its agreement is under question. Andrew Hill, a University of Liverpool pharmacologist and co-author of the British paper, evaluated the cost of the Merck pill, concluding with his colleagues that the company is charging wealthy countries like Canada approximately $898 per course of Molnupiravir. 

 

Convenient, easy-to-take oral treatment to prevent hospitalization and death in the unvaccinated and "breakthrough" vaccinated patients is generally viewed as an important medication.

Pfizer has also announced its creation of such a pill and its product was the more impressive of the two, in that its Paxlovid was seen through trials to reduce the risk of hospitalization for high-risk unvaccinated patients given the pill five days within exhibiting symptoms by 88 percent. The U.S. Food and Drug Administration granted it approval on Wednesday.

Molnupiravir was originally developed as a possible antidote to an encephalitic-causing virus, at Emory University, and then as a flu treatment. It was transformed from flu to a COVID treatment once the pandemic began, with Merck partnering with Ridgeback Biotherapeutics. The drug interferes in RNA replication, inhibiting reproduction of the virus.

Merck announced October 4 that its drug cut hospitalization in 762 unvaccinated patients with such risk factors as cancer and obesity by a substantial 50 percent, then halted enrolment of new patients through its multi-country MOVE-OUT trial which randomly assigned patients to Molnupiravir or a placebo within five days of symptoms appearing. However, when results returned on the other 646 already enrolled patients, the benefit shrank to 30 percent, only just qualifying as statistically significant.

Added to which the surprising outcome that patients in the second half of the group who received a placebo performed better than those who received Molnupiravir -- effectively reversing the first-half results. 15 patients of the 322 on placebo ended up in hospital, while 20 of the 324 drug-treated patients were hospitalized. A rather inexplicably awkward turn-about. "That almost never happens", concluded Dr.Hill.

Dr.Hill recommended that rather than buying the Merck drug, Canada should turn to investing in fluvoxamine, a generic anti-depressant that the Together trial headed by Dr. Mills found to reduce hospitalization in similar patients by a like 30 percent, but at a much smaller fraction of the cost.

 Merck’s experimental oral COVID-19 antiviral drug, Molnupiravir.  Credit...Merck