Making innovation count: Managed Access Programmes for medicines

With all the complexities of the modern global pharmaceutical market, it is sometimes easy to overlook basic principles.

The long years of discovery and development, as well as millions of dollars in investment, that may or may not result in a viable new medicine mean little if that product does not reach the patients who really need it. Yet even when a drug has secured regulatory approval and is entering markets around the world, there is no guarantee that every eligible patient will have a chance to benefit from it.

A number of factors play into this disparity. It may reflect fluctuations in patient demand through the product lifecycle, selective registration strategies, or product discontinuation by the licence holder in some markets.Alternatively, early promise in clinical trials can ratchet up pre-approval demand, especially when the target condition is critical or poorly served. Patients in these circumstances may not have access to a clinical trial, whether down to geography or exclusion criteria in the study protocol. Or if the medicine is already on the market, some patients may live in remote areas beyond the reach of standard commercial routes.

ACCESS LAG

Patients may also find there is a substantial lag between approval and availability, created by national pricing and reimbursement negotiations or a growing trend to impose a ‘third hurdle’ of health technology assessment.

According to the European Federation of Pharmaceutical Industries and Associations’ latest Patients W.A.I.T. (Patients Waiting to Access Innovative Medicines) Indicator, there may be an average delay of anything from 88 to 392 days between marketing authorisation (MA) and completion of pricing and reimbursement procedures in 11 European countries excluding Germany and the UK . (These data refer to new medicines available in 2010 for prescribing under national healthcare provisions, after gaining marketing authorisation from the European Medicines Agency during the years 2007 to 2009.)

The proportion of medicines with a valid MA available commercially in these countries ranged from 39% in Portugal to 86% in Greece. And the hiatus between approval and access is even more pronounced in other markets around the world. On top of this, there may be national, regional or local variations in access due to formulary restrictions, budgetary constraints or cost-benefit assessments – increasingly so as healthcare systems worldwide buckle under the weight of population ageing and its associated burden of chronic disease.

DIGITAL DRIVER

Any of these barriers can mean enormous frustration, both for patients who know there are more effective therapies out there yet cannot use them, and for physicians who feel a professional, ethical and emotional obligation to make sure their patients receive optimal treatment. Those frustrations are heightened in an extensively networked digital age, where patient awareness and expectations of better treatment options are fired up by a constant stream of news coverage or dialogue through social media.

According to research from the Pew Internet & American Life Project in the US, as of December 2012 67% of adult internet users were tapping into social networking sites. Just as health information has been a strong driver of internet usage overall, so it is proving to be a rich source of conversation in the social space. A PwC survey of US adults found that around one third of them were using social networks online for health discussions.

This is a global phenomenon, in the same way that mobile phones are transforming health systems and access to healthcare in developing countries with large rural populations. In the UK, for example, the NHS Choice website gets more than 10 million ‘hits’ a month, with 74% of patients using the service before seeing their GP and 40% logging on either as an alternative to, or to reduce their reliance on, GP consultations . A more informed, confident, networked patient is all the more likely to question why they do not have access to the best available medicine for their condition.

This presents a marked challenge to physicians, especially in a constrained economic environment where prescribing freedom is increasingly circumscribed by cost-effectiveness considerations, and where the desire to treat optimally may run counter to budgetary realities at local level.

Similarly, the pharmaceutical and biotechnology industries are under growing pressure to deliver a broad package of value to healthcare systems and patients, extending beyond the traditional parameters of quality, safety and efficacy. One way they can do this is by making the best possible use of exceptionalaccess mechanisms that really put the patient first. Companies need to make this a strategic imperative, though, rather than dealing with it on a piecemeal basis if and when the need arises. Patient demand for innovative medicines can start to gather pace well in advance of drug approval, continuing all the way through the lifecycle beyond product discontinuation.

"JUST AS HEALTH INFORMATION HAS BEEN A STRONG DRIVER OF INTERNET USAGE OVERALL, SO IT IS PROVING TO BE A RICH SOURCE OF CONVERSATION IN THE SOCIAL SPACE."

PLUGGING THE GAP

The standard formula for access to medicines from discovery onwards is that the volume of patients using the drug increases as it moves from Phase I testing into larger efficacy trials, then continues to grow with initial and subsequent commercial launches. In reality, though, patient demand for medicines that address an unmet medical need often runs ahead of the levels of access a company can provide through traditional channels. If patients with unmet medical needs feel they need to look outside the clinical trial or commercial settings to secure drug access, there is a risk they will resort to informal and potentially unstable distribution channels, particularly over the internet – channels that may be increasingly vulnerable to counterfeiting or product adulteration.

Yet other options exist to plug gaps in demand outside traditional access routes. These Managed Access Programmes (MAPs) are an ethical, secure and properly regulated means of fulfilling sporadic, urgent or unconventional demand for medicines.

Moreover, they can be established and administered globally, either on a patient-by-patient basis or for specific patient cohorts, by specialists who understand and provide the necessary focus, flexibility, insight and assurance to administer MAPs with optimal sensitivity and effectiveness.

MARKET TO MARKET

One compelling reason for calling on specialist expertise in this area is that the way managed access is handled in regulatory terms varies from market to market – even within the European Union, where there is nominal harmonisation of the criteria and systems for developing, marketing and distributing medicines. In fact, the very term ‘managed access’ encompasses a variety of circumstances and mechanisms whereby needed drugs can be supplied to patients outside the framework of commercial distribution or clinical trials.

It may refer to medicines that:

• are still in clinical development;
• may never be approved but retain medicinal value for a very small population (e.g., certain orphan drugs);
• are approved only in selected markets;
• have been discontinued in a particular market;
• provide an alternative to a drug that has been discontinued worldwide;
• are used off-label in some countries.

There are indications that many companies have already started thinking about MAPs as an integral component of their product development and commercialisation strategy. Market research conducted by managedaccess specialists Idis suggests, for example, that around 48% of companies consider using Managed Access Programmes during Phase III/IIIb clinical trials and about 10% of them do so during Phases I and II.

Moreover, in around 38% of cases, companies will implement a MAP so that patients who do not meet the eligibility criteria for a clinical trial still have access to the investigational drug. Withdrawal of effective medication once a clinical trial is completed can be ethically fraught, especially in critical conditions and/or in countries where patients’ only access to modern – or indeed any – therapy may be by enrolling as a trial subject.

Traditionally, Open-Label Extension Studies have addressed this dilemma. Yet maintaining post-trial access in this way until a drug is commercially available can be an expensive remedy. Companies may also prefer to allocate the internal resources required to other areas of their business. Research indicates that roughly 64% of companies will use a MAP to maintain access to medication for patients at the end of a clinical trial; 77% do so to ensure that non-trial patients get necessary medicines while an approval application is under review; and 30% to meet patient needs after halting product development.

MAP MECHANISMS

The mechanisms used to enable MAPs around the world may be characterised as “expanded access” or “named patient”; “temporary authorisation for use”; “compassionate use”; or “early access”.

In the United States, ‘expanded access’ (formerly ‘compassionate use’) regulations in place since 1987 allow patients in some circumstances to obtain drugs or biologics for treatment purposes, subject to specific criteria and approval requirements. Access may be permitted under a single-patient or emergency IND (investigational new drug application); under programmes for small to intermediate groups of patients; or via a treatment IND or treatment protocol for larger patient cohorts. Typically, a medicine considered for expanded access in the US market will have shown efficacy in later-stage clinical trials, as well as evidence of safety.

In Europe, Managed Access Programmes are available under an assortment of rubrics, including ‘named patient’ programmes, where doctors request access to a specific medicine on behalf of an individual or ‘named’ patients; ‘named patient supply’; ‘compassionate use’ programmes; or ‘autorisations temporaires d’utilisation’ (‘temporary approvals for use’ – France).

Moreover, the regulations governing these procedures differ widely among the 30 countries making up the European Union and the European Economic Area due to variations in national medical practices, available resources and funding, insurance systems or hospital structures.

Comparable access programmes operate outside the US and Europe. In Canada, for example, non-marketed drugs are available under a ‘Special Access Programme’ to healthcare practitioners treating patients with serious or lifethreatening illnesses, where conventional therapies have failed, are unsuitable or are unavailable. In Australia, individual patients may be prescribed experimental drugs via the ‘Special Access Scheme’, while a ‘Named Patient Access’ mechanism performs a similar function in Japan.

MAPs provide access under specified circumstances not only to investigational drugs in clinical development but to products already available in other countries but not yet approved in the patient’s home market. Where a medicine (e.g., an orphan drug for a rare disease) is targeted at a small patient population distributed across several countries, a Managed Access Programme offers an alternative when seeking marketing authorisation and launching in individual markets is neither practical nor financially viable for the company concerned.

"MANAGED ACCESS PROGRAMMES …PROVIDE STRUCTURED AND ETHICAL ACCESS TO MEDICINES FOR UNMET MEDICAL NEEDS, ADMINISTERED IN FULL COMPLIANCE WITH LOCAL REGULATIONS."

STRUCTURED AND ETHICAL

Managed Access Programmes are developed and managed in partnership with pharmaceutical and biotechnology companies. They provide structured and ethical access to medicines for unmet medical needs, administered in full compliance with local regulations. These programmes are not a substitute for clinical trials: indeed, in some cases they may help to improve patient recruitment into existing trials. The core objective is to make medicines available to those patients who have exhausted all treatment options in their own country.

Beyond the crucial driver of ensuring patients in need have access to optimal therapy, MAPs do offer ancillary benefits to all healthcare stakeholders, including physicians, health systems and the companies that develop and market the medicines. For example, Managed Access Programmes can help to build awareness of new therapies among the medical community and to develop valuable relationships with key opinion leaders (KOLs). More specifically, they provide training for early-adopting physicians in appropriate and optimal use of a new drug – a particularly important consideration in oncology and other therapeutic categories that often rely on complex treatment regimens.

MAPs also help to consolidate relationships with patient-advocacy groups, opening up a further conduit to patients, KOLs and other healthcare providers. These organisations can support educational initiatives associated with product use through MAPs, manage expectations around access programmes and parallel clinical trials, or facilitate pre-screening of patients for inclusion in MAPs.

BUILDING VALUE

In addition, Managed Access Programmes are a source of cost-benefit data for health technology assessments or of early ‘real-world’ insights into treatment and usage patterns. This information can then be used to optimise product experience and therapeutic value in broader patient populations. As cost pressures on healthcare systems build relentlessly, regulators and payers alike will increasingly look for evidence of how medicines perform outside the relatively narrow and controlled parameters of clinical trials designed to generate safety and efficacy data for market authorisation.

MAPs represent the first opportunity to observe how a drug actually works in a real-world patient community. Such real-world data gathered during a MAP could provide crucial insights which could benefit patients, regulators, physicians and companies alike. Further, real-world data gathered by a specialist MAP provider could help to elucidate efficacy in patient subgroups or to clarify safety signals in actual use. This real-world data may also offer strategic insights – into treatment pathways, off-label use or geographical variations in demand, for example – to underpin internal decision-making and planning by the licence holder.

THINK STRATEGICALLY

The fragmented landscape for MAPs described above underlines the importance of thinking about exceptional access strategically and at an early stage of the product development process, so it can serve as a tool to inform decisions throughout the drug lifecycle.

Pharmaceutical and biotechnology companies that manage access programmes internally on an ad hoc basis often find they lack the necessary budget and resources to respond efficiently and effectively to surges in patient demand. Meanwhile, the clock may be ticking for critically ill patients. Assigning responsibility to a specialist provider such as Idis, with the experience to navigate complex national variations in the regulatory procedures and market conditions for MAPs, allows the manufacturer to allocate budgets proactively for access management.

It also means internal resources can focus more productively on regulatory approvals and planning for commercial launch, rather than being distracted by a function for which they may lack any real expertise. Ideally, a strategic approach will consider the need for a Managed Access Programme for each investigational drug in the pipeline, and at as early a stage as Phase I-II clinical trials.

GOOD FOR EVERYONE

Proactive attention to MAPs enables companies to respond swiftly and ethically to any demand for access within pre-established frameworks and through stable, co-ordinated channels of supply. That is good for the patient and good for the prescribing physician. It also validates the product supplier’s commitment to better healthcare for all and in any circumstances, beyond any immediate considerations of revenue or market share.

As pharmaceutical and biotechnology companies grapple with how to deliver true value and long-term patient outcomes that will help beleaguered healthcare systems manage escalating costs and demand, MAPs are a way of yoking corporate social responsibility to awareness-raising that clears a space for innovation where it is most needed. Above all, these programmes re-assert industry’s fundamental role in maintaining a flow of new therapeutic options that can really make a difference, in the right place and at the right time, to patients who may have felt they had no alternatives left.

Idis has more than 25 years’ experience of working in partnership with pharmaceutical and biotechnology companies to develop and implement customised Managed Access Programmes for thousands of medicines across a wide range of therapeutic categories worldwide.