COVID-19 puts a spotlight on the Medicines Patent Pool

LONDON — In Kenya, parents used to cut up adult antiviral pills for their HIV-positive children, roughly working out how much their infant should take based on their body weight, despite the risk of inappropriate dosing.

“It was very painful,” said Nelson Otwoma, an advocate for people living with HIV, “but if they didn't do that, kids were dying as infants. ... The doctors' advice was that it was the only way to help a child.”

Although pediatric antiretroviral medications were available, they were too expensive and difficult to access for most people. But since 2010, the work of the Medicines Patent Pool, or MPP, has facilitated the development of generic drugs for HIV, tuberculosis, and hepatitis C, allowing them to be sold at an affordable price. To date, MPP says it has delivered nearly 12 billion doses of medicines across 131 countries.

MPP was created in 2010 by Unitaid, an international project for financing HIV, malaria, and tuberculosis treatments. As it approaches its 10th birthday in July, the model has hit the spotlight amid heated discussions about how to make any potential COVID-19 treatments and vaccinations more accessible. In particular, campaigners have been calling for patents — which protect intellectual property — to be pooled in a mechanism such as the COVID-19 Technology Access Pool, or C-TAP.

MPP, staffed by just 25 people — a mix of scientists, policy wonks, business specialists, and others — has been doing this for a decade with patents, although not with other types of intellectual property that C-TAP plans to share, such as regulatory data. While there is not yet widespread agreement on how to make tools for beating COVID-19 accessible, MPP’s mandate has already been expanded to cover the illness.

“The model is: The MPP approaches the originator companies, the ones who invented new drugs, and asks them for a license,” said Charles Gore, the group’s executive director. That allows MPP to make agreements with various generic manufacturers to produce a drug and sell it more cheaply in certain places.

Gore said the reasons these companies decide to give away licenses to MPP vary and include wanting to contribute to public health, but it can take two years and a lot of negotiation.

Researchers including Ken Shadlen, professor of development studies at the London School of Economics, said pharmaceutical companies often lack the financial incentive to produce drugs for low-income markets where profit margins are slimmer. Big pharmaceutical companies only have to negotiate with MPP once and can still receive royalties, which is easier and faster than doing numerous sublicensing deals with generic drug manufacturers. Royalties are agreed on a case-by-case and are paid by the generic manufacturers but tend not to be “very significant — 3 to 7%,” according to Gore.

Gore continued: “Once they’ve given us a license, we then invite generic manufacturers to submit an application to manufacture high-quality but affordable versions of the drug that can then be sold in low- and middle-income countries. … Our licenses are nonexclusive, so we have a number of generic manufacturers that we give sublicenses to. They then compete among themselves to drive down the price.”

MPP’s aim is to make prices as low as possible while ensuring the generic companies can make a “reasonable profit” so that the model remains sustainable, Gore added. He said MPP actually provides commercial advice to the generic companies it works with. “Their commercial interest and our public health interest mesh,” he said.

Using this method, the pool has secured licenses for a plethora of HIV medicines — including pediatric formulations — three hepatitis C drugs, and a tuberculosis drug. By late 2019, at least 5.1 million HIV-positive people in 97 lower-income countries had access to the antiretroviral drug dolutegravir, according to MPP, which signed a license for the drug in 2014 with pharmaceutical company ViiV Healthcare.

The pool has been well received by academic experts in intellectual property. It “fulfills an important role and provides a good model for other initiatives,” according to professor Duncan Matthews, director of the Queen Mary Intellectual Property Research Institute at the University of London.

“I’m a big fan,” LSE’s Shadlen agreed, calling MPP a “brilliant innovation.” He praised its commitment to transparency — all of the pool’s licenses are published on its website — which it pursues to a degree “which is new in this area,” he said.

That is important because the “devil is always in the detail of a contract,” such as how long a license lasts, royalty terms, what formulations it includes, and other production information, Shadlen said. These details can contain information on the prices that drugs are sold for in low-income countries but are not usually publicly available. “If you want to understand prices … there’s just missing information if you don’t have access to the license,” Shadlen said.

But he also outlined an “Achilles' heel.”

“There’s always a lot of — particularly middle-income — countries that are left out,” he said. This is because, despite significant populations living in poverty in these countries, pharmaceutical companies also perceive them as a potential market for their drugs and so do not always include them in an MPP license.

Shadlen added that only the patent holders — usually big pharmaceutical companies — could solve this problem. “It would be great if the MPP allowed a sublicensee to produce the drug and sell it to Mexico or Brazil or Colombia. … But they are typically not the countries that are going to be included in these licenses,” he said.

Gore “absolutely” agreed that MPP has not managed to reach as many countries as it would like. “But at the end of the day, we don’t have, per se, enormous leverage. If a company says, ‘We are not going to give you a license for X [middle-income] country and we know … there are still huge numbers of people there who are extremely poor and in need of this but there’s not really much we can do about it,’ it’s up to the company.”

He said a more general consensus that provision must be made in these licenses was needed to tackle the issue.

The pool has not run into any significant conflict with the organizations it works with and takes care to assess the generics companies to which it issues licenses for their capacity, skill sets, and history, according to Gore.

“The reason we don’t have issues ... is we believe we are doing a service to Big Pharma,” by managing licences for them for free, he said. MPP’s work is funded by Unitaid, the Swiss government, and Wellcome. “It's a service to them, and we’re giving to generic companies an opportunity to make ... reasonable returns. Hopefully, what we do is win-win for everyone. And yet we’re enabling something that wouldn’t happen without us.”

On March 31, the pool’s mandate was expanded to include medications developed for treating COVID-19 and now also includes vaccines, diagnostics, and medical equipment to treat it. “The public health licensing part [for this] is very similar, even if a lot of the specifics are different,” Gore said.

Licensing to MPP forms part of C-TAP’s Solidarity Call to Action, and the organization has also been in talks with various countries, health organizations, and pharmaceutical businesses about its work. That includes conversations with Gilead about its COVID-19 treatment remdesivir — although the company recently made its own deal with generic manufacturers on this — and MPP is in “early discussions with a number of companies,” according to Gore.

The pool most likely has a role in one of the many projects designed to manage the pandemic but is still confirming how it will work in the COVID-19 world, he said, adding that there are three scenarios for how MPP sees its near future.

In the first, where the enormous political will galvanized by the pandemic “fizzles out,” MPP goes back to its normal work with just a few additional COVID-19 licenses.

In the second, the huge momentum is sustained and MPP becomes the main pool for all coronavirus-related intellectual property.

The third scenario — “somewhere in the middle” — is most likely, Gore said, and will require some limited expansion of the pool’s staff.

But beyond that, Gore said that there are exciting things on the horizon for MPP and that the pandemic would not stop it from doing other work. One element of this is an ongoing shift to increase the pool’s advocacy work for access to medicines — particularly in its pursuit of licenses for longer-acting drugs for HIV, tuberculosis, and hepatitis C, which require fewer doses and corresponding trips to clinics.

Back in Kenya, Otwoma agreed this simplicity — compared to the “cocktails” of HIV drugs people used to have to consume — is “lifesaving.”

“One pill daily means … people like taking it better, it’s improving adherence and therefore quality of life,” he said.

If MPP hadn’t stepped in, “even today we would not [have] ... a generic version” of single-dose HIV drugs like dolutegravir, Otwoma said. “People are now able to get the best drugs available in generic versions.”