SA must decide whether to buy a Covid drug that costs thousands per person – but takes less than R200 to make

By Joan van Dyk for the Bhekisisa Centre for Health Journalism

19 Aug 2020

This medicine has been shown to slash Covid recovery times by more than a quarter. But who will be allowed to get it once it’s available in South Africa’s hospitals? And how does it work?

Remdesivir can cut three days off Covid-19 patients’ recovery time in hospital, a May study shows. The medicine is critical for South Africa’s fight against Covid-19 since the country has so few intensive care beds, and to support local research into how well the drug will work in African populations, some experts argue. Most research, however, has been conducted among white patients in the US and Europe.

Meanwhile, the committee tasked with writing South Africa’s treatment guidelines on remdesivir doesn’t think it’s a good fit for the country given its high cost. The committee issued its recommendations in April and an updated version in June. South Africa has access to a generic version of the medicine, but even this cheaper version can cost more than R10,000 per person for a treatment course.

What is remdesivir?

Remdesivir is an antiviral drug that has been around since 2009 — it has never been used to treat any conditions, but has been studied as a potential treatment for several diseases. It has been tested to treat Ebola and two earlier coronaviruses, SARS-CoV which causes Severe Acute Respiratory Syndrome and MERS-CoV, the virus that leads to Middle East Respiratory Syndrome. The medicine didn’t work well for Ebola, but researchers found remdesivir to be somewhat effective against SARS-CoV and MERS-CoV in animals, although that research never progressed to human trials. That is why scientists thought it might help to fight SARS-CoV-2, which causes Covid-19.

In April, the preliminary results of a study showed that it helped hospitalised Covid-19 patients recover more than 25% faster than patients who didn’t get it. The results of the randomised controlled study — the gold standard for determining cause and effect relationships during which one group receives the drug and another a dummy drug — was published in the New England Journal of Medicine.

By 1 May, just two days after the research showed promising results, the United States medicines regulator, the Food and Drug Administration (FDA), had approved remdesivir for emergency use for children and adults hospitalised with Covid-19.

An emergency use authorisation is a tool that allows the FDA to make unapproved medicines available in the US during a public health emergency.

The European Medicines Agency in June and the Therapeutic Goods Administration of Australia in July authorised the medicine for provisional use, which means it is approved for use based on less comprehensive data than usually required. The preliminary data must, however, show that the benefits of using the medicine outweighs the costs and more data must eventually be provided.

More than 1,000 people from 10 countries including the US, Mexico, the United Kingdom and Japan took part in the New England Journal of Medicine study.

About half the participants were given remdesivir in a drip for 10 days, or until the person was discharged from hospital or died. The remaining participants were given a salt water solution as a placebo.

Participants who were given remdesivir took about 11 days to recover, while those who got the dummy drug took approximately 15 days.

The study showed Covid-19 patients who were less sick when they were first given remdesivir fared better than those with severe symptoms that required them to be ventilated, suggesting that the medicine is more effective earlier on in the disease progression. Researchers however note that the group that had the best reaction to the medicine — those who were hospitalised but only needed oxygen — were also the biggest group.

The study found remdesivir had no effect on whether patients die from Covid-19 or not, which led the scientists to conclude that it is clear that treatment with an antiviral drug alone is not likely to be sufficient.

How does it work?

When SARS-CoV-2 enters a person’s system, the virus breaks into human cells in the lungs or intestines, for example. Once inside, the new coronavirus hijacks a specific part of the human cell where it injects its own genetic material. Then, the virus will start giving orders from inside the unsuspecting human cell to make copies of itself. But the newly copied cells won’t be human lung or intestine cells, they’ll be more SARS-CoV-2. The next order will be for the lung cell to melt away, after which the coronavirus particles will then be sent out into the bloodstream to hack more human cells.

Remdesivir interrupts this process, and interferes with the cycle the virus uses to make copies of itself and spread in the body.

As a result, the person is likely to be less ill with Covid-19 since there is less of the virus in the person’s system to fight.

3 Which Covid-19 patients will be given remdesivir?

South Africa’s latest Covid-19 treatment guidelines don’t recommend the use of remdesivir. A June rapid review of the medicine recommended that it should not be used to treat hospitalised Covid-19 patients requiring oxygen or ventilation.

The review was conducted by a subcommittee of the health department’s ministerial advisory committee on Covid-19 tasked with writing guidelines to treat the disease. The subcommittee is still waiting for a response from the health department.

Why doesn’t the subcommittee think remdesivir is a good idea?

While cutting three days off a hospital stay may benefit individual patients, it’s not enough to recommend remdesivir on a population level, explains Tamara Kredo, a senior specialist scientist at the South African Medical Research Council and a member of the subcommittee that wrote the report.

Given that many hospitalised Covid-19 patients in South Africa who receive oxygen or are on ventilators, stay in hospital for 10 days in any case, in order to receive a full course of another drug called dexamethasone, that can reduce mortality among ventilated patients by one third and by one fifth in patients receiving oxygen, “getting patients out sooner might not be the most important thing” explains subcommittee member and University of KwaZulu-Natal senior pharmacy lecturer Andy Gray.

Remdesivir also comes at a high price tag and each patient who would like to use the drug, would have to apply to use the medicine from the South African Health Products Regulatory Authority (Sahpra). “This could affect fair access to the medicine,” Gray says.“What’s more, Cipla’s initial offering was only enough for 5,000 patients – but which ones?”

Francois Venter is the divisional director of Ezintsha at Wits University’s faculty of health sciences. Venter is also a member of the health department’s ministerial advisory committee on Covid-19.

If South Africa follows the US Food and Drug Administration’s guidelines, most hospitalised patients could need remdesivir, Venter argues, since people here are likely to be sicker by the time they reach a health facility than they would be in countries such as the US and the UK where the New England Journal of Medicine study was conducted in April.

Research has been under way since July to test whether an inhaled version of remdesivir administered in a nebuliser, a device that is also used to treat asthma, may be able to help Covid-19 patients recover too. If that works, Venter explains, people could be given the medicine far earlier by their general practitioner.

The problem with intravenous remdesivir, Venter says, is that patients have to get it at a healthcare facility with the right gear to administer it.

“It severely limits the usefulness of the medicine to patients who are very sick.”

4.Why does South Africa need this medicine?

Remdesivir is a “big breakthrough” for Covid-19 patients, Venter argues, especially given how few intensive care beds there are in South Africa. South Africa has between 3,500 and 4,000 ICU beds in private and public hospitals, depending on which data is used to calculate the total.

He explains: “Most people will recover well, but for the people who need oxygen or who are on ventilators this medicine is a huge help. People are being lukewarm about [remdesivir’s effectivity].”

Over the past three weeks, South Africa’s recorded Covid-19 cases have been steadily declining, especially in the provinces hardest hit by infections such as Gauteng, the Western Cape and the Eastern Cape, the country’s official data shows. KwaZulu-Natal may reach its peak soon, Health Minister Zweli Mkhize announced early in August.

Venter says the worst may already be over for South Africa. “By the time we have the drug [remdesivir] ready much of the damage will have been done.”

But the Covid-19 disease will nonetheless be around with us for the foreseeable future, he says, and remdesivir still has a crucial role to play for patients, the health system, and research.

South Africa needs local research to determine how well remdesivir will work on its population — and that’s another reason why we need the drug on local soil, Venter says. The New England Journal of Medicine study’s participants were mostly white (50%). Black people made up 20% of participants and Asian and Hispanic people made up 13% and 20% of participants respectively.

“The same thing happened with HIV treatment,” Venter explains. “Antiretrovirals were only being tested in white, gay men. The side effects on black women were completely different and more severe.”

Is there enough of the medicine to go around?

The US bought three month’s stock, or 500,000 doses of remdesivir from drugmaker Gilead Sciences in June, which amounted to most of the world’s supply, The Washington Post reported.

Nine generic companies including Cipla and Mylan have a licence to manufacture a generic form of Gilead Science’s medicine in 127 developing countries, including South Africa, according to a company statement.

In July, Cipla South Africa got what’s known as a Section 21 authorisation to import remdesivir from Sahpra. This tool allows doctors to import unregistered medicine into the country on a compassionate basis. That means each patient will need to apply to be treated with remdesivir, Gray explains.

A vial of the medicine will go for $55, or R960 in both the public and private sectors in South Africa, says Cipla South Africa’s communications manager Fidelia van der Linde.

Each patient will need between five and 11 doses, depending on how sick they are, so treatment from Cipla could tally up to about R10,000 per person.

The health department has started negotiations with drugmakers to find out “how low they’re willing to go”, Venter says.

“The cost is a big concern.”

Cipla’s drug costs seven times less than the original from Gilead Sciences, which set its price at R6,800 per dose for the US government and other developed countries. US health insurance companies are coughing up nearly R10,000 per vial.

The generic is still expensive, Venter says. “It’s dirt cheap to make.”

If the generic drug is sold at cost (without a profit), it should cost about $10, or R175 for a 10-day course, according to an independent analysis published in May by the Institute for Clinical and Economic Review.

Cipla South Africa says its price is “on par with other developing or emerging markets.” DM/MC

(Updated 14:17 19 August 2020: This article was updated to state that the European Medicines Agency approved remdesivir for provisional use and not emergency use as previously stated. Additional comment was added to reflect rapid review advice on the use of remdesivir by a subcommittee of the health department’s ministerial advisory committee on Covid-19. In addition, the article now reflects that Section 21 approval from the South African Health Products Regulatory Authority can only be used by individual patients and not by companies as previously stated.)

This story was produced by the Bhekisisa Centre for Health Journalism, http://bhekisisa.org. Subscribe to the newsletter http://bit.ly/BhekisisaSubscribe.

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