In early 2020, as a deadly new coronavirus began to spread around the world, pharmaceutical company Pfizer Inc. set up a team of elite scientists and chemists to identify ways to treat COVID-19.
The pharmaceutical giant from the United States, which began exploring the development of a vaccine, also wanted to produce a pill that would stop the infection from spreading, much like the drug Tamiflu is used to fight the common flu. The team did research to find unused components of the molecules that would help start the process, and very quickly identified a promising candidate, writes Reuters.
More than a year later, Pfizer has not yet begun large-scale trials for oral treatment of COVID-19, but says it hopes such trials will begin in July.
Pfizer and its rivals, including US-based Merck & Co Inc. and Swiss pharmaceutical company Roche Holding AG, are vying to produce the first antiviral pill people can take once they have the first signs of the disease. . These companies share a goal: to fill a hole found in the treatment of COVID-19, helping people who have recently been infected with the coronavirus not to become seriously ill and seek hospitalization.
But after almost 18 months of the pandemic, there is still no easy-to-administer treatment that has been shown to be effective against COVID-19, the disease caused by the coronavirus. This is due to the fact that a number of effective vaccines against COVID-19 have been developed, including the vaccine that Pfizer has developed with its German partner, BioNTech, which received authorization for use in the US in December last year.
Pfizer’s experience is evidence of the challenges pharmaceutical companies face in developing oral treatments for the virus. Unlike the vaccine, which should only boost the body’s immune system, an effective antiviral pill should block the spread of the virus throughout the body and at the same time, be selective enough to avoid interference with healthy cells.
Testing antivirals is also difficult, say company executives. A medicine should be taken at the initial stage of infection, meaning that for large-scale trials, people who have recently been infected with COVID-19 should be found. Many people who become infected with coronavirus show only mild symptoms, but studies should prove that the pill has a significant impact on a patient’s health.
Pfizer chief executive Albert Bourla said the company would seek emergency authorization in the US to use the COVID-19 pill by the end of this year at the latest.
“Right now, we have good reason to believe we can be successful,” Bourla said last week, speaking via video link at an economic forum in Greece.
Pfizer and his rivals say the pill development process is faster, as it used to take several years to produce a pill.
The companies Merck and Roche have recently launched large-scale human trials and have also said that their pills will be ready for use later this year. Merck is developing the drug in collaboration with Ridgeback Biotherapeutics LP and Roche is working with Atea Pharmaceuticals Inc.
Governments around the world have given billions of dollars to develop vaccines, but Pfizer, Merck and Roche say they have not received government funding to develop COVID-19 pills.
“In search of the new Tamiflu”
While the rate of coronavirus infection in some states has dropped, some other states are facing rapid spread of the virus. Moreover, many countries are facing a shortage of vaccine supplies and according to the trend, most citizens of the world will not be able to be vaccinated for several years. Many people, however, are determined to get the vaccine.
Scientists predict that COVID-19 – which has killed more than 3.5 million people worldwide – could turn into seasonal illnesses, just like seasonal flu.
“We need a medicine that will keep people out of hospitals,” said Dr. Rajesh Gandhi, a professor and specialist in infectious diseases at Harvard Medical School.
Doctors have tried a number of existing pills to treat COVID-19, but none of them have shown success during rigorous clinical trials.
Currently, the only method that is showing that it is helping COVID-19 patients to avoid hospitalization are antibody medications, which require intravenous infusions. But, this type of treatment does not work so well against the coronavirus variants.
Pifzer and his rivals say the antiviral candidates, taken in pill form, may be effective against a wider range of coronavirus variants, but companies have not released data on these claims.
For patients already hospitalized for COVID-19, treatment includes steroids or anti-inflammatory medications to manage the symptoms of the infection. But these drugs do not directly attack the virus. The only drug approved in the US for the treatment of COVID-19 is Remdesivir, manufactured by Gilead Sciences Inc. This medicine is given intravenously and is used only for hospitalized patients.
Gilead is currently testing Remdesivir for some form of inhalation and is looking for other ingredients that may be effective agents.
“We are all looking for the new Tamiflu,” said Gilead Health Chief Merdad Parsey.
Tamiflu is recommended for people who have seasonal flu symptoms for no more than two days and this medicine has been shown to shorten the duration of flu symptoms.
Pfizer scientists and chemists began research into antiviral treatment in January last year. They soon focused on an ingredient they had discovered in 2003, when the company was conducting research into the SARS pandemic, says Charlotte Allerton, who heads Pfizer’s drug design department.
This ingredient belongs to a class known as protein inhibitory agents, designed to block a key enzyme, or protein, that is essential for the coronavirus to be able to multiply. Similar drugs are used to treat other viral infections such as HIV or Hepatitis C, combining them with other antivirals.
Pfizer scientists, however, faced a challenge. Laboratory tests showed the drug was active against the new coronavirus, known scientifically as SARS-CoV-2, but the concentration of the drug’s components was not strong enough to fight the virus in the human body, Allerton said.
Pfizer continued to work with an active component of that ingredient to create a drug that could be given intravenously. But antivirals are most effective if the disease is in its early stages, and to fight the disease, it is not “easy to do through an intravenously administered drug,” Allerton said.
In March 2020, Pfizer scientists also began designing a compound that is absorbed through the stomach and taken as a pill, and according to Allteron, the scientists, in July, finalized the design of this pill.
The discovery of an inhibitory agent, which could be taken in pill form, “was more or less like a masterpiece of chemistry,” said Pfizer chief science officer Mikael Dolsten.
The development of antivirals is more complex than that of vaccines because they must target the virus, which is already in the human body replicating in its own cells but without damaging healthy cells. Vaccines against COVID-19 usually teach the human immune system to recognize and attack a part of the protein that is specific for the coronavirus.
A COVID-19 pill would probably only have to be taken by patients for a few days, but pharmaceutical companies have had to work slowly to produce this pill in order for it to be safe.
Merck and Roche pills, unlike Pfizer, use other mechanisms to prevent the virus from multiplying. But, all companies have the same challenges when it comes to testing.
One of them is to make sure patients take the pill very soon after being infected with the coronavirus.
“It all lies in treating the disease at its earliest stage, when the virus is spreading,” said Dolsten of Pfizer.
And with high vaccination levels in some regions, clinical trials of the pill need to be done in some states, where COVID-19 continues to spread rapidly.
In March of this year, Pfizer launched the first human phase trial in the US for its COVID-19 experimental pill, known as PF-07321332. Also last fall the company conducted another test for the drug that is given intravenously.
Dolsten declined to comment on how the final trial phase of these two drugs will be conducted.
Merck antiviral drug, called Molnupiravir, has recently faced a challenge. The company said last month it would not use the pill on hospitalized patients. But the company said it would conduct the final phase of trials, which would include a small number of patients who were not hospitalized – especially those who had symptoms of COVID-19 for no more than five days. and that participants in these trials must have at least one risk factor for serious illness, such as advanced age, overweight, or diabetes.
The Merck company said it will have accurate data from these tests, in September or October.
Meanwhile, Roche and Atea have also limited the number of participants in the final stage of their rehearsals. Their pill, called AT-527, will be tested on patients who have symptoms for at least the last five days. Atea said that the results of these tests are expected to be released by the end of this year./ REL