Home Resources Market access in Brazil – All eyes on Spinraza

Market access in Brazil – All eyes on Spinraza

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In April 2019, Brazilian Health Minister Luiz Henrique Mandetta announced a pilot agreement for access to Biogen’s Spinal Muscular Atrophy (SMA) treatment Spinraza (nusinersen) through the Sistema Único de Saúde (SUS). This is the first agreement in Brazil to include a risk-sharing model, in which the government only pays for the drug if there is improvement in the patient’s health.

In a country where it typically takes years for innovative pharmaceutical products to be reimbursed in the public sector, manufacturers wishing to obtain market access for their products in Brazil will be watching this example closely to see how it plays out.

SMA is a rare generic motor neuron disorder that affects approximately 7 to 10 babies in every 100,000 live births (although there are not currently any epidemiological studies specific to Brazil). It usually results in death less than two years after birth. Until recently, there were no approved therapies to treat the condition. Spinraza, approved by the FDA in 2016, represents one of a new wave of drugs that are extremely expensive (one of the most expensive drugs in the world), indicated for a very niche population, and with uncertain long-term benefits due to the lack of long-term safety and effectiveness data. Given the high unmet need in the SMA patient population, the drug’s profile lends itself to an outcomes-based contract.

The risk sharing pilot project drafted by the Ministry of Health provides Spinraza free of charge for patients with specific SMA subtypes, with evidence generated during the three-year duration of the pilot project to be submitted to CONITEC for re-evaluation. Disease registries are being planned to enable long-term follow up of SMA patients. It will be important to establish such registries for other rare diseases in order to support the information architecture required for the successful implementation of future agreements.

A key point to consider in the coming to fruition of this agreement is the role of patient advocacy. Biogen have suggested that the results of a public consultation, which received a record number of contributions, were central to the Ministry of Health’s decision. Manufacturers wishing to gain market access in Brazil have long worked with patient advocacy organizations to support their cause. It seems that in this case, the work done by patient advocates in educating payers on the disease and its burden on the lives of patients and their care partners was critical to help them realize the potential value of the treatment.

Risk sharing agreements
In recent years, alternative payment models have become increasingly discussed in Brazil, as a way of rethinking how high-cost drugs are funded.  As a 2017 EURORDIS (Rare Diseases Europe) reflection paper ‘Breaking the Access Deadlock’ suggested, today’s challenges will not be solved by applying yesterday’s conservative mindsets.

However, until recently, Brazilian regulations did not permit risk-sharing negotiations or proposals to be put forward in the context of new drug evaluations. These types of market access agreements therefore rarely formed part of the discussion. The pricing process was clear: ANVISA considers safety, efficacy and price, using international reference pricing. CONITEC then uses cost effectiveness data to define whether the drug should be incorporated into the SUS. No official cost-effectiveness threshold is considered.

Rapid changes in the landscape are underway, with multiple new proposals being brought to the table. Risk sharing agreements, which first originated in Europe and Australia, have become increasingly common in many countries, including the US – although there remains considerable confusion about the terminology. A range of plans have been drawn up requiring the manufacturer either to provide their drug for free if no improvement is seen after a certain timeframe (based on mutually agreed outcomes, at either a population level or an individual patient level), or reimburse additional procedures if they continue to be required despite treatment with their product.

A notable early example is the Multiple Sclerosis (MS) Risk Sharing Scheme, established in 2002 by the National Institute of Clinical Excellence (NICE) in the UK to allow people with MS to access disease modifying therapies they deemed to be clinically effective but not cost effective, while long-term cost effectiveness was assessed through monitoring studies. Manufacturers agreed to lower their prices later should the data collected deviate from the predictions.

Offering a risk-sharing agreement can help to overcome payers’ challenge of uncertainty about how a new drug will perform in their patient population in the real world, and manage the budget impact of offering a new therapy by limiting patient access.  For manufacturers, such an agreement can be offer the opportunity to get their drug onto a formulary that it would not otherwise have been included on -– and therefore to patients it would not have been able to reach, at least not so quickly, while protecting the price by offering indirect price benefits.

However agreements of this nature constitute a huge administrative burden that can be challenging to implement. This is especially true in a middle-income country such as Brazil where infrastructure to monitor patient outcomes is limited, governance is complicated due to the multiple stakeholders involved, and there is a shortage of qualified researchers to manage such schemes or draw conclusions from the long-term data collected.

Context: A brief history of healthcare in Brazil
The 1988 Brazilian Constitution established that the State is responsible for providing universal and equal access to health services for every Brazilian citizen. The Brazilian health care system therefore comprises a mandatory, tax-financed unified public system (the SUS) as well as an optional, premium-based private health care system that is frequently provided through employers. The SUS is beset by structural problems, capacity constraints and inadequate financing, and has a reputation for inconvenience and long waiting times. Higher income Brazilians therefore typically opt for private care. As a result, the proportion of the population covered by private health insurance has expanded from 17.6% in 2000 to 22.8% in 2017. This makes Brazil the second-largest private health insurance market in the world after the US. Uniquely for a country with a universal healthcare system, a higher proportion of healthcare spend is private rather than public.

The Ministry of Health is responsible for the development of a formulary that lists the drugs to be made available to the entire Brazilian population at no cost to the patient. This Essential Medicines List is known as ‘RENAME’, and it contains drugs that are approved by the Brazilian regulatory agency Agência Nacional de Vigilância sanitária (ANVISA), have proven effectiveness, and are indicated for diseases that affect a large population. An additional specialized program (CEAF) covers high-cost drugs that, after evaluation by the Ministry of Health, are considered effective and needed, and must also be provided to the population with no co-pay.  This includes drugs for treating approximately 80 diseases, including rare diseases and those targeting small groups, such as Crohn’s disease, viral hepatitis C and multiple sclerosis.

Availability of medicines in the public sector has however long been an issue, with stock shortages a major concern. Although recent data indicate improvements in access over the last decade, the system is bureaucratic and the public health budget has faced a series of cuts, with many new requests blocked or delayed.

CONITEC, which was created as a formal HTA body, advises the MoH on the incorporation of new drugs and procedures into the SUS’ Clinical Protocol and Therapeutic Guidelines (CPRG) based on a scientific, evidence-based approach, including at least partial health economic evaluation. In the three years from July 2012 to July 2015, out of 199 requests to incorporate medicines into the SUS via CONITEC, 112 (56%) were blocked, 66 (33%) were still under analysis and only 80 (40%) were incorporated. Tellingly, 45 of these were therapies that had been available in the market for over 15 years. Only 13 were medications launched within the last 5 years.

These roadblocks have resulted in the proliferation of alternative strategies to gain access to medicines.

One option is to go through the private sector. All private health insurers must provide their enrolees with drugs that are included on a standardized list of procedures issued by the National Agency of Supplementary Health (Agência Nacional de Saúde Suplementar, or ANS, the private health regulator). It is therefore strategically important for manufacturers to get their products included on this list – once substantial real world experience has been built up with a drug in the private sector, this can then be used as evidence to make a stronger case for incorporation into the SUS later down the line.

A second option is to set up named patient programs and patient access schemes in order to establish real world effectiveness in a small number of patients prior to requesting incorporation. But the third route, which is growing in popularity, is the judicial channel. This involves patients pursuing access through the court system, on the grounds of their ‘right to health’ as defined in the 1988 Constitution. Since the 1990s, such claims have been increasing exponentially, and the vast majority of judicial decisions are favorable to patients. Demonstrating high sales through this route may again support future reimbursement in the public sector. Claims are increasing the pressure on health budgets in an unpredictable way, making them difficult to manage. In 2018, Ministry of Health data shows that “health judicialization” cost the government R$1.4 billion (370 million USD), of which 87% was spent covering the ten most expensive drugs for treating rare diseases. These ten drugs were provided at an average cost of R$ 759,000 per patient (200,000 USD) to 1,596 patients – a tiny drop in the ocean relative to Brazil’s population of almost 215 million.

Earlier this year, restrictions were imposed to prevent the supply of high-cost drugs not registered with ANVISA in an attempt to go part of the way to managing these claims, which are increasingly threatening equitable public health care delivery. With the private sector covering only a higher income minority, and the judicial route also favoring richer patients with the resources to turn to the court, it is clear that new mechanisms are needed to create a more sustainable solution that can enable more patients to access new, effective and innovative drugs within the limited healthcare budget available. This need is intensified given the number of Advanced Therapy Medicinal Products (ATMPs) emerging on the horizon.

Conclusion: What impact might this agreement have? 

It is too soon to tell how the demands of executing this risk sharing agreement might impact sales based on the paperwork required to apply for access at provider and pharmacy level. And what Brazilian payers’ appetite will be for similar agreements going forward, remains to be seen.  At a global level, while learnings can be drawn from other schemes, there is no gold standard in how such agreements should be implemented, and the costs of implementation and monitoring also need to be considered.

With Novartis’ gene therapy Zolgensma (onasemnogene abeparvovec) also being approved for the treatment of SMA by the FDA in May, again with high uncertainty with respect to the duration of benefit, and many more AMTPs for more common conditions set to gain regulatory approval in the coming years, demands such as this one are only likely to increase, and a broader dialogue about how therapies of this nature will be funded is underway.

The success or failure of this agreement will show if risk sharing has the potential to become a new paradigm in Brazilian market access. However the challenge in countries such as Brazil is that market access agreements such as this Spinraza risk sharing scheme do not directly address the root issue, which is affordability.

In a country where it typically takes years for innovative pharmaceutical products to be reimbursed in the public sector, manufacturers wishing to obtain market access for their products in Brazil will be watching this example closely to see how it plays out.

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