Subscribe Now

By entering these details you are signing up to receive our newsletter.

Early access essentials for the rare disease community

Kieron Lewis, director of strategic consulting at Clinigen tells us about the importance of Early Access Programmes in the rare disease space. 

The past decade has seen rapid development in the field of novel drugs and therapeutic agents, particularly for rare and ultra-rare diseases
Kieron Lewis

The past decade has seen rapid development in the field of novel drugs and therapeutic agents, particularly for rare and ultra-rare diseases. Despite the remarkable innovations that have taken place, licence approval for many of these promising therapies remains both time consuming and costly. The challenges in access to treatment can have a serious impact on outcomes and patients’ overall quality of life. The only hope for patients who cannot access treatment via a clinical trial is through early access routes that allow the treating clinician to consider an unlicensed or investigational medicine. 

​Are we speaking the same early access language? Early Access Programmes (EAPs) can be referred to in multiple ways, depending on terms used in local regulations and on company, healthcare professional and vendor preferences. Some of the terms that you might hear include: Early Access, Managed Access, Compassionate Use, Named Patient use, Expanded Access, Pre-approval Access, unlicensed access. 

Kieron Lewis, director of strategic consulting, Clinigen

In the past, clinical trials were the only way for patients in many countries to access drugs under development. However, not every patient meets enrolment criteria for specific clinical trials or lives in a country where the trial is recruiting. As a result of this unmet medical need, since the late 1980s, Early Access Programmes (EAPs), have opened doors to more possibilities for such physicians and their patients.

Since 2010, the number of requests for unlicensed treatments has risen by nearly 25%, and a major proportion of these requests are from rare disease patient populations, owing to highly engaged patients and caregivers connected to advocacy groups. ​

The past decade has seen rapid development in the field of novel drugs and therapeutic agents, particularly for rare and ultra-rare diseases

Initiating an EAP is a way of making use of regulated routes that exist in countries around the world to address the “access gap” that arises at any time during a drug’s lifecycle when patient demand exceeds patient access for a treatment. When a company establishes an EAP it is in response to unmet medical need and demand amongst the disease community, and usually to achieve one or more of the following objectives: 

1. To make a treatment in clinical development available to patients who are unable to participate in a clinical trial. This is of critical importance in rare disease where often the number of trial sites and countries recruiting patients into a study may be limited.

2. To make a treatment available to study participants after the completion of a study, but before it becomes commercially available—this can be called a Post-Trial Access Programme. This is paramount in rare disease, as the treatment may be the only available option globally, especially for an ultra-rare disease.

3. To make a treatment that has been approved in one country available in a country where it has not yet been approved. EAPs can be used to bridge the gap between first approval of a rare disease treatment, and subsequent approvals which may come many months later; local pricing and reimbursement delays can make routine access even longer to establish.

4. To make a treatment available in a country where the company is unlikely to be able to support commercialisation. Where rare disease companies are small biotechnology firms, they might not have the resources or global footprint to have operations in all countries where patient demand exists. An EAP can help get treatment to more patients globally, in response to demand and in a cost-effective way.

5. To make a drug available after commercialisation in a specific market, if a rare disease treatment has been terminated but some patients are still benefiting and need to remain on treatment. In this case it is not “early” access as such but rather “late” access. In many countries the same regulatory frameworks are used to enable this type of access in response to requests from physicians. An example in rare diseases is where companies invest research and development into repurposing an existing treatment for development in a new indication. Sometimes this leads to the old indication being withdrawn, which can leave patients exposed if an alternative route for access has not been established.

Q.How many patients? EAPs can be implemented on a patient-by-patient basis, or, in some countries, for a group of patients, based on local regulations. For rare diseases where patient numbers are low, in many countries an EAP might proceed on an individual patient basis, at least at first. Some notable exceptions are Germany and Belgium, where a group of patients would need upfront approval from the local authority. 

Q.Who requests access? Requests for access to an unlicensed medicine must be made proactively by a healthcare professional, as unlicensed or investigational medicines cannot be promoted in any way. Most physicians treating rare diseases will have an awareness of both licensed and unlicensed treatment options available due to the specialist nature of the patients they manage. The physician may also be prompted by the patient to discuss a treatment in development that is not yet licensed and would clearly discuss the risks, benefits and rationale for considering such an approach. An early access route would only be considered in serious or life-threatening conditions where no suitable licensed alternative exists. The approval process would be driven by the physician and usually supported by the pharmacist, who would seek approval from the local health authority once they have confirmed that the manufacturer has agreed to make the treatment available despite being unlicensed. This process varies from country to country and can take anything from a few days to a few weeks. Once approved by both the manufacturer and the health authority, local importation and shipment to the hospital can be arranged, either by the manufacturer or a service provider like Clinigen.

Q. Who pays for these medicines? Companies who permit access on an unlicensed or pre-approval basis will sometimes charge (where regulations allow), and sometimes provide them for free. This very much depends on the cost of treatment, the number of requests they expect, duration of treatment and the physician’s ability to claim reimbursement at local level. Also, for many small companies, the cost of development is so high that running a free supply program may not be financially viable. In this case charging is used to help fund or offset the EAP. Reimbursement for prescribing an unlicensed treatment can be complex and varies from country to country. Generally, the more developed healthcare systems in richer countries will have processes and funds that make reimbursement more likely. In these cases, the physician is more likely to prescribe if funding is available to pay for the treatment, either via private insurance or a specific hospital fund.

Q.What data are collected? Another side benefit to providing access to patients in this way is the opportunity to collect what is called real-world data or real-world evidence (RWE) from an EAP. This helps companies learn more about how their treatment is used outside of clinical trials prior to commercial launch, which is valuable to both them and regulators, who will assess both clinical trial data and RWE during the licensing process if this is applicable.

Who is Clinigen? 

Clinigen’s mission is to get difficult-to-access medicines to patients that need them globally. Clinigen helps supply more unlicensed or investigational medicines to eligible patients that urgently need them than anyone else, however challenging the circumstances. We provide healthcare professionals with ethical, compliant and timely access to treatments where no suitable licensed alternative exists, often in life-threatening situations where the medical need is urgent. 

We are also the global leader in providing services to pharmaceutical and biotech companies to help them address their access to medicine challenges. We do this by providing strategic advice and consulting services on the regulations and legislation and the policies that companies need to have to govern these EAP decisions and ensure transparency. We can also hold stock of the treatment, distribute globally through our own supply chain network, collect real-world data, and manage all interactions with healthcare professionals on behalf of our client companies using our online ordering platform and global 24-7 multilingual customer services team. Alongside this, we look to support fruitful engagement with patient advocacy groups, healthcare professionals, regulators and payors. All of this is part of Clinigen’s commitment to getting the right medicine to the right patient at the right time.

If you are a pharmaceutical or biotech company developing medicines within rare diseases and you would like to talk to Clinigen and access our support, please contact Kieron Lewis:

If you are a member of a patient group interested to learn more in this area during 2021, click the button below to find out more about the Clinigen Patient Advocate Fellowship in early access.

For more information about Clinigen:

Skip to content