Exploring Latin America In The COVID-19 Era

Unique industry partnerships and new regulatory flexibility in Latin America may help to improve access to medicines, even as COVID-19 wreaks havoc in the region’s largest pharmaceutical market. Can biopharma’s bespoke solutions to market access barriers coalesce into a strategy capable of overcoming political, economic and COVID-19 related risks?   

• Specialty drugs and biologics often are not covered by public health systems in Latin America, a region comprised of 20 countries and 640 million people. Amgen Inc. is using its biosimilar portfolio to create a footprint in new Latin American markets.

• COVID-19 is instigating regulatory flexibility in Latin America; health authorities have adopted electronic submissions and other online tools. Brazil, Argentina, Colombia and Peru have published guidance for remote patient monitoring in clinical trials.

• Patients with chronic and rare diseases have faced interruptions in access, as health systems prioritize patients with COVID-19. In some countries, patients can’t get access to a stable internet connection, even where telemedicine and other virtual services are offered.

At the BIO 2020 conference in June, which was held virtually due to the COVID-19 pandemic, speakers on a panel about the impact of coronavirus on health care delivery worried aloud about a coming reduction of public funds for medicines in the US and Europe. An economic recession, speakers feared, could lead to reductions in drug coverage and cost containment measures in the world’s largest markets. To prevent a tightening in market access, the biopharma industry will have to “find innovative solutions ourselves and collaborate with health systems and policy makers to enact them,” said Stefan Neudoerfer, senior director, head of market access Europe, CSL Behring.

This strategy – of creating solutions in collaboration with key stakeholders in individual markets – is already playing out in Latin America, where public funds for innovative medicines have always been a challenge to secure, and where private insurers, which cover a much smaller slice of the population compared with the US or Europe, are pushing back against rising costs associated with an increase in specialty drugs and rare disease products. In Brazil, the private insurance market, which is primarily offered through employer plans, covers roughly 25% of the population, with public health care funds covering the remaining 75% of the population, says Elvin Penn, general manager, Amgen Brazil.

 

 

Elvin Penn, general manager, Amgen Brazil

"With the COVID-19 situation, there is more pressure on the [Brazilian] government in terms of budgets and resources available to treat patients." 

In Mexico, where Penn was previously Amgen’s general manager, only around 6% of the population is covered by private insurance. In both countries, “the public system is always more restrictive, has less availability of resources, and a lot more demand because most of the population depends on the public system,” said Penn. “And the level of funds changes, because it depends on the economic situation, and in some cases it depends on administration in power at a given moment,” said Penn. “With the COVID-19 situation, there is more pressure on the government in terms of budgets and resources available to treat patents.”

For Amgen, one of the world’s largest biologics companies, Latin America –a region with a population of 640 million people across 20 countries –  is “one of our fastest growth regions,” said Ian Thompson, Amgen’s SVP and intercontinental general manager. “But it also comes with some volatility.” The combination of growth potential and challenging access conditions has led to the development of innovative solutions for patients in the region. “Some of our best ideas, some of our brightest young talents, and some of our most interesting collaborations are coming out of Latin America,” said Thompson. “Ideas and platforms and initiatives that began in Latin America are now becoming standards of excellence across the business.” Thompson cited a patient support platform in Colombia that manages patient information, privacy and compliance requirements, which is now being replicated in other parts of the world.

Ian Thompson, SVP, intercontinental general manager, Amgen

“Ideas and platforms and initiatives that began in Latin America are now becoming standards of excellence across the business.”

Amgen is also leveraging its biosimilars portfolio as a tool for market access in Latin America and has 15 different biosimilar products approved across several countries. In 2019, Amgen Brazil entered into a formal Productive Development Partnership (PDP) with Libbs Farmacêutica, a private Brazilian company, and the Instituto Butantan, a public research institute, which will create the first local manufacturing capacity for Amgevita, a biosimilar version of AbbVie’s Humira (adalimumab). The 10-year agreement will allow Amgen to make imported supplies of Amgevita available to patients immediately, with a transition plan to transfer the technology into Brazil when the local manufacturing infrastructure comes online, Penn says. The cost of adalimumab and other biologics account for over half of the Brazilian Ministry of Health's annual drug budget, and biosimilars are a strategic priority. The PDP is Amgen’s first partnership of this kind in Latin America. “We’re very excited about it, because it will give us the opportunity of make [Amgevita] available for the patients in the public system,” he said.

Biosimilars are helping to create a pathway into new markets in Latin America, especially when paired with value-based partnerships, notes Thompson. “We’re able to enter some Latin American markets quickly post loss of exclusivity because of the affordability component … it’s a way to establish a footprint in some of these markets. Biosimilars drive competition, and competition creates more affordable options,” he said.

Amgen is involved in 44 “innovative contracts” across the Latin American region, including in Brazil, Mexico, Colombia and Argentina, with a variety of payers, says Thompson, who described the partnerships as requiring both parties to put some skin in the game. “The nature of our value-based partnerships requires rigorous compliance and legal/regulatory sign-off, so it’s a slightly different pathway compared with a standard discount or volume-based approach,” said Thompson. “They are bringing value and we do see them reducing costs, improving care, and enhancing the patient experience.” Thompson highlights that the contracts are active in multiple markets, touching roughly 40,000 patients and 16,000 health care practitioners, and including cardiovascular and oncology products, among others.

The key to setting up innovative contracts, says Thompson, is tailoring them to the needs of the individual institution or stakeholder. “Our cross-functional team will seek to understand the challenge [a stakeholder] is trying to overcome, how can we ensure patients that need this product can get it, when they need it. Stakeholders sit down together and work out very often a unique pathway,” he said. “In some situations, it might be a rebate or a concession at the end of the year, but it might be something completely different, it could focus on services or education. What would be a great outcome for the institution, for the insurance company, for patients, and how can we make that work together?”

Like other companies, Amgen has dramatically reduced face-to-face contact with physicians. “Net-net, we are still down in the number of interactions we’ve had, which does have an impact on some products, but our teams have been very resourceful and customer-focused in adjusting their communications to provide information services, particularly COVID-19 related services to customers that make inquiries about it,” said Thompson. “We’ve been very pleasantly surprised by our ability to bring large audiences into virtual congress seminar type activities. We have attracted higher numbers of customers to an event - say for example in Mexico City - then you'd be able to get live, because of traffic restrictions and congestion restrictions. We've had meetings where we've had over 1,200 people attend and participate fully and engage really well, and that's been very effective.” Amgen has also run advisory boards and large-scale launches – Thompson said the company had successfully launched “a couple of products virtually” – which is important, since “it’s going to be part of the new normal.” However, some markets in Latin America are more equipped for digital engagement and multi-channel marketing than others, said Thompson.

Protecting patients’ continuity of care is another chief concern during the pandemic; unusual times call for unusual measures. In Brazil, the frequency of commercial flights has dropped precipitously, which has affected the availability of flights for Amgen’s drug distribution. The solution? “We have been using other channels for distribution, specifically charter flights, so that our patients continue receiving our drugs with no interruption,” said Penn. “That has required some additional effort from our supply chain team, but our patients have continued to receive the drugs as well as the service levels we offered before the crisis.” Chartered flights for drug distribution may not be a sustainable long-term strategy but figuring out how to send medications to patients’ homes, a common practice in many mature markets, becomes critical during a pandemic. “Hospitals have been a key component of COVID-19 transmission, so sending medicines to patients’ homes when suitable, as opposed to putting patients and nurses at risk of contagion, should be an important lesson learned,” said Thompson. “I think there is potential for the industry to help rebuild a more resilient health care ecosystem, and partner with health care ecosystems, to ensure this resilience is built in so that it is perhaps less easily penetrated by something like Covid-19 in the future.”

Regulations In Flux

Health authorities in Latin American countries, in the past, have not been known for their speed of regulatory action. Prior to the pandemic, regulators in many Latin American countries required the submission of paper documents and ink signatures. Additionally, the interpretation and roll out by global regulators of an international Identification of Medicinal Products (IMDP) has not happened yet. “We really want to see regulators come together on this,” said Ronan Brown, SVP, head of IQVIA integrated global compliance.

Before the biopharma industry switched its focus to specialty and rare disease treatments, Argentina and Brazil were critical markets for conducting large hypertension or diabetes clinical trials, said Brown. “But they would take 12 to 18 months to come online, so unless your recruitment period was two years, at minimum, you’d really struggle to include Latin American countries,” he said. With smaller trials for rare diseases, Latin America has been left behind, due to the decrease in clinical sample sizes needed, and costs of work for running those studies.

From Patients To Policy Advocates

The Latin American Patients Academy (LAPA) is a non-profit group aimed at “building and facilitating strategic alliances between civil society leaders and public health decision makers in Latin America.” On a panel with other patient advocates during the BIO 2020 conference, Eva María Ruiz de Castilla, LAPA’s founder and director, said the COVID-19 pandemic had been difficult for patients in Latin America, many of whom were struggling with a good enough internet connection to speak with a physician, despite a rapid expansion in available telemedicine services. But the organization has had some successes, such as in Colombia, where patients organized a recurring meeting with government officials, every 15 days, for updates on the current situation and to learn how patients can help.

Access to medicines was a LAPA priority, said Ruiz de Castilla, since hospitals and other health care facilities have largely transformed into COVID-19 centers for care. “Chronic and rare disease patients aren’t able to get access to the same services as in the past.” Transportation was an issue, and LAPA has been working to get ambulances to bring patients in for infusions, Ruiz de Castilla said. In Brazil, ride-share services such as Uber and Cabify have entered into collaborations with hospitals and other facilities in order to safely deliver patients for treatment, such as chemotherapy. As physicians and health care systems in Latin America shifted to caring for COVID-19 patients, they had forgot about other diseases beyond COVID-19, she said.

On clinical trials, one of LAPA’s objectives is to bring Latin America’s regulators in line with other geographies, to match the speed with which other regulators make decisions. “To us it’s very important to get access to clinical trials, it’s an opportunity for patients, and a learning opportunity for physicians and researchers, so we are advocating for more access to trials.” The challenge, said Ruiz de Castilla, is that “information about clinical trials is limited, and when we get the information, it’s too late for us to help patients access the trials. We need to help the system go faster, and we need to get the right information at the right time.”  (Also see "Expanding The Tent: Improving Trial Participation Among Under-Represented Patient Populations" - In Vivo, 8 Apr, 2020.)

Stronger, broader collaboration is at the top of Ruiz de Castilla’s wish list. She said, “The pandemic is showing us great examples of global, and local, collaborations, ways of working in which patients are at the center or are at least involved. New ways of working in partnership are being discovered, and we are all working toward the same objectives,” she said. “If we don’t collaborate, everything will take longer.” 

A potential silver lining of the COVID-19 pandemic can be seen in recent actions taken by regulatory authorities in Latin America. Cammilla Horta Gomes, Latin America regulatory policy lead at Roche, Brazil, detailed numerous regulatory changes and flexibilities across Latin America in a recent webcast with Alberto Grignolo, editor-in-chief, DIA global forum and corporate vice president at Parexel. “In Latin America, some authorities are adopting very interesting approaches to come up with alternatives to the challenges they’re facing,” said Horta Gomes. “Regulators want the continuity of R&D but at the same time they may have to deal with a sudden surge of new clinical protocols because of pandemic. They must ensure a minimum normality in their regulatory processes, but also deal with urgent demand for applications, and they have deal with doing it from home. They also have to maintain access to products when global supply chains are complete disorganized.”

Horta Gomes noted that the most common change among regulatory bodies across the region was the adoption or increased use of online tools, email and electronic platforms, both for the submission of documents, and for conducting virtual meetings with applicants. Other changes per Horta Gomes, some formal and some informal, include:

• Honduras and El Salvador are now allowing digital submissions during the pandemic.

• Peru and Uruguay are handling pharmacovigilance reports online exclusively.

• Colombia and Chile formally waived requirements for wet signatures.

• Regulators in Brazil and Colombia (Anvisa and Invima, respectively) adopted the Pharmaceutical Inspection Commission (PIC/S) GMP reliance initiative, as well as mutual recognition of foreign manufacturing inspections from member countries.

• Brazil’s Anvisa formally introduced a resolution allowing the possibility of remote inspections, or inspections by video conference.

• Argentina joined the WHO’s COVID-19 Solidarity Clinical Trial.

• Brazil, Argentina, Colombia and Peru published guidelines for patient remote monitoring in clinical trials.

• Costa Rica began granting extensions for marketing authorizations.

• Argentina, Bolivia, Brazil, Colombia, Peru and other countries are prioritizing assessment and approval of COVID-19 related products.

Horta Gomes believes the three most important areas for regulatory action in Latin America include GMP certifications, and establishing reliance or recognition mechanisms, such as certificates issued by PIC/S members; reliance schemes for the registration of new products approved in mature markets like the US and Europe; and post-approval changes for repurposed products, which may be already authorized for use in other countries, but are now being repurposed for the prevention or treatment of COVID-19. “Reliance for this post-approval scenario might even be more important than reliance pathways for new products,” she said. “Reliance,” which denotes the total acceptance of another regulator’s decision, is different from recognition, which is a regulator’s decision to accept a specific regulator’s decision, or part of a decision. 

Building A Market

Given the challenge with public health funding and resources in many Latin American countries, companies may choose not to go to the trouble of registering an innovative product in Bolivia, for example. But specialty and rare disease products are urgently needed in many emerging markets, since “those patients are no different from patients in California, London or Paris,” said Zulf Masters, CEO of Masters Specialty Pharma, a private pharmaceutical and distribution company focused on emerging markets. Masters specializes in local knowledge of emerging markets, including Latin America, and operates in 75 countries. When reached for an interview with In Vivo, Masters was in the process of sourcing 5 million rapid COVID-19 tests for Brazil, a task he described as “a rapidly moving target.”

Masters’ business model involves partnering with biopharmaceutical companies to either distribute their products in emerging markets under an exclusive distribution deal, or by working with local health authorities to secure expanded access for patients. For companies focused primarily on mature markets, Masters helps to grease the wheels in emerging markets, in terms of regulatory clearance and sales and marketing. Years ago, said Masters, health authorities in emerging markets recognized “this big juggernaut coming along” in the form of expensive specialty therapies and biologics. “That was not sustainable to the public purse … the public sector [in many emerging markets] only looks at a fraction of the disease populations.” In sickle cell disease, for example, Masters said “our studies in northeast Brazil showed us that the recommended treatment for the population should be 30% coverage of the product. And yet, Brazil can only afford 8.33% of coverage.”

For cash-strapped public insurance systems, Masters conducts health care technology assessment modeling to determine how a partner company might offer tiered pricing, as a way in. The company also works with patient advocacy organizations, charities and foundations, as well as large government buying organizations or group purchasing organizations, to understand unmet need in a particular market. “We go to the health authorities or the ministries and look at their repositories and data, and mine that data for need assessment,” said Masters.

Since many orphan diseases have a genetic component, genetic testing will increasingly become the first step to establishing a new market. “That’s the first thing you build: you put the lab in, put the tests in, encourage testing, and then with testing you have a patient population that’s eligible for your product,” said Masters. “That is exactly what Genzyme and Shire have done.”

Masters is not involved in genetic screening but said the company was “talking to small, innovative biotech companies in Cambridge, Massachusetts, who have drugs on the horizon that will require setting up local testing and local labs.”

Masters founded the company 35 years ago, after working as a rep in the Caribbean for the Beecham Group, and noticing that poor countries, like Haiti, “were completely forgotten by the first world nations and the major pharmaceutical companies.” He said local knowledge and a relationship with regulatory groups are the most important lubricants for market access in emerging markets. “A lot of people will tell you that [Brazilian regulator] Anvisa is very challenging … you mention Anvisa and say, ‘I don’t want to go there.’ But we’ve made it our mission over the years to learn and work with these health authorities, and to find out exactly what they want,” said Masters. “At the end of the day, there’s a reason behind what they want. If you can understand that and interpret it correctly, it’s not a problem.” Interestingly, it is not the emerging markets that represent the challenge, it’s getting the drugs from large pharmaceutical companies, and ironing out an agreement – especially for specialty and rare disease products,” he said. 

COVID-19 As Opportunity

Brazil in particular has fared poorly in the pandemic, and the situation is not improving. COVID-19 modeling from The Institute for Health Metrics and Evaluation (IHME), at the University of Washington, predicts that COVID-19 deaths in Brazil will surpass US deaths by the end of July. For companies launching COVID-19 clinical studies, Latin America may serve as a good location for recruitment. Assuming that additional treatments for COVID-19 enter the market, and hopefully, a safe an effective vaccine, manufacturing and distribution will be the next big challenge. Regulators in Latin America and elsewhere must be “willing to use stickers, for instance, they will have to be tolerant with some text deviations, and maybe they can consider facilitating the implementation of electronic labeling,” said Roche’s Horta Gomes. 

In interviews with In Vivo, Penn and Thompson at Amgen said it was too soon to discuss COVID-19 distribution strategies for Latin America. There are over 500 product candidates currently being tested against COVID-19; many will not make it to the finish line. Infectious disease vaccines are not a high margin product category for the biopharmaceutical industry, but it is heartening to see the level of global collaboration, and participation, from the industry. “We have an opportunity, an obligation, a responsibility, to work as hard as we can and as collaboratively as we can to bring potential solutions to market,” said Thompson. “It's quite risky. Once solutions are found, making those treatments available and not restricting them because of geography or cost or price, will also be important.”

“I think it's shown what is possible when people put their minds together with respect to removing barriers,” said IQVIA’s Brown. “What we're seeing in the last three months has been that the regulators have moved heaven and earth to accelerate potential treatments. I would love to see this carry over into other studies and into the future when we're not in a pandemic situation.” However, Brown noted the safety implications inherent to a potential vaccine, which would go to hundreds of millions of people in a short amount of time. “You need real-time safety data to be able to asses what’s going on, nobody is really talking about that yet. Knowing that vaccines are some of the less profitable products the biopharma industry makes, maintaining a low-cost safety system for a low margin product, or even a loss-making product, will be key.”