Early Access Programs, also known as special access programs, give patients access to medicines for life-threatening diseases where there are currently no treatment options prior to regulatory approval or when they are in the late phase of clinical trials. This is a great win-win situation for all stakeholders in the healthcare industry. Patients get earlier access to innovative and, in some cases, life-saving medicines. Physicians can thus offer an additional treatment to their patients if the existing treatments cannot meet disease unmet need. Pharmaceutical companies can benefit from generating additional data, which facilitates their pricing and reimbursement (P&R) negotiations with payers. Also, that allows them to build and maintain relationships with key opinion leaders (KOLs), who can then become brand advocates. Early access programs are also beneficial for payers as they allow them to evaluate medicines based on additional real-world data and make more informed decisions when it comes to P&R of medicines. However, obtaining early access is not easy as it requires comprehensive planning and a convincing evidence package. That is why, the key question that many pharmaceutical companies ask themselves is “What are the key considerations that need to be kept in mind to ensure successful early access”?
What are the key characteristics of an Early Access Program?
Not every drug is eligible for an Early Access Program. To qualify for such a program, a drug needs to meet a number of eligibility criteria which vary across countries. However, as a whole, early access programs are intended for treatments for life-threatening conditions for which there is no licensed alternative available in a given country1. The two main Early Programs in Europe are the Compassionate Use Program (CUP) and Named-Patient Program (NPP) (Table 1).
Compassionate Use Programs (CUPs)
CUPs are early access programs which are intended to facilitate the access and availability of innovative treatments to patients suffering from life-threatening conditions where there is no adequate treatment option, and a patient is not eligible to enrol in a clinical study. CUPs are typically conducted in the early stage of the product development cycle which allows patients to get access to these medicines in their pre-launch stage, while they still undergo clinical trials but have not been authorised in a certain country. In the past, clinical trials were the only way for patients to access treatments which are still under development. However, clinical trials are associated with rigorous inclusion criteria so many patients would not qualify to enrol in them. CUPs allow these patients to receive a treatment, which in some cases, may save their life outside clinical studies. At a European level, CUPs are governed by the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency, which sets the laws and recommendations for them. However, every EU member state has their own legislation for the use and implementation of CUPs that pharmaceutical companies need to adhere to2. The CUP applies for a group of patients in a selected clinic or hospital and is typically initiated by the manufacturer.
Named-Patient Programs (NPPs)
NPPs are an early access opportunity intended for medicines which are not authorised for use by patients in their home countries. They can be initiated only by physicians who draft requests on behalf of specific or “named” patients who otherwise would not have access to an effective treatment. It is also the physician who bears the liability for this program in case anything goes wrong with it. Whilst CUPs allow physicians or manufacturers to apply for a group of patients as long as all of them meet the eligibility criteria of the program, NPPs are always implemented on a patient-by-patient basis3. To be eligible for a NPP, the treatment should be approved in at least one country from which it could be imported. The NPP can be a suitable option for drugs which are approved elsewhere but not in the patient’s country, have been discontinued or are in short supply in the patient’s country. To qualify for a NPP, a patient should meet the same requirements as for a CUP – suffer from a life-threatening or seriously debilitating condition for which there are no currently authorised effective treatment and be ineligible to enter the clinical study for this treatment.
|Criteria||CUP (EU)||NPP (EU)|
|Legislation in place||Article 83 (1) of Regulation (EC) No 726/2004||Article 5 of Directive 2001/83/EC|
|Who initiates the program?||Manufacturer/group of physicians||Physician|
|Criteria to define patient population set by||Manufacturer / CHMP||Manufacturer/ Physician|
|Who can benefit from the program?|
Limitations of use?
|Group of patients i.e. more than one (permission is granted to a hospital as opposed to a particular patient)||Named patient basis; physician makes an individual request for every patient|
Abbreviations: CHMP: Committee for Medicinal Products for Human Use; CUP: Compassionate Use Program; EAP: Early Access Program; FDA: Food and Drug Administration; NPP: Named patient basis;
How to successfully plan an Early Access Program?
From a manufacturer perspective, planning an Early Access Program is a very challenging activity because of the multiple stakeholders involved. An early feasibility assessment of an Early Access Program (at least 6-12 months before the expected demand) should be considered and if a manufacturer decides to move forward, a robust and comprehensive business case should be developed with inputs from different departments, including Market Access, Marketing, Medical, Regulatory etc.
The success of an Early Access Program is dependent upon many factors including robustness of clinical results of the investigational drug, its access and commercial strategy, level of awareness and adoption by KOLs, duration and markets of the early access programme, robustness of manufacturer supply chain, continuity of safety data collection etc. Such programs are heavily dependent on KOLs as they are very often responsible for their initiation. Therefore, it is crucial for manufacturers to have an experienced Medical Science Liaison (MSL) team who should build and maintain strong relationships with KOLs and patient advocacy groups in the therapy area of interest4.
What are the key challenges when planning an Early Access Program and how can they be resolved?
To be able to plan the implementation and logistics of an Early Access Program, manufacturers should have a very clear understanding of the prevalence of the life-threatening condition and the precise number of patients, which are likely to enrol in their Early Access Program. They should also be certain that there is an interest from patients and/or KOLs in getting access. If manufacturers rush with their ambition to initiate such a program without thorough consideration of its protocol and implementation, the Early Access Program could have a negative impact on patient and KOL experience and diminish the pharmaceutical company’s reputation. Moreover, an inadequately planned Early Access Program may turn out to be a waste of resources and more importantly provide suboptimal treatment to patients in need. For this reason, it is advisable for manufacturers to collaborate with advisors or consultants who can support them with the right planning of such a program and set accordingly their expectations on potential uptake.
Another major challenge with Early Access Programs currently is the disrupted supply chain across the world caused by the Covid-19 pandemic. There is currently a global shortage of different substances and reagents, resulting in impaired manufacturing capacity. Moreover, there are often delays with the logistics and transportation of medicines across countries. As a consequence, many Early Access Programs are failing as pharmaceutical companies are unable to manufacture and deliver the necessary volumes of drugs on time in many countries, including Canada, Australia, South Korea etc. Therefore, manufacturers need to make sure they have a robust supply chain in place before they commit to an Early Access Program.
In conclusion, Early Access Programs have become a standard part of the development and launching of new medicines. However, the successful implementation of such a program requires careful planning and collaboration with many stakeholders. Although in essence pre-marketing authorisation programs seem beneficial for everyone, there are cases when they would not be the most appropriate option. For example, if the main driver of the pharmaceutical company is generation of revenue or there are challenges with its supply chain, an Early Access Program could only harm their reputation and bring no value to patients. That is why manufacturers should conduct a comprehensive analysis of the disease landscape, build strong relationships with KOLs in the therapy area and have a reliable partner to advise them on the planning of their Early Access Program to ensure its successful implementation.
- Bell S., 2016. When is an Early Access Program not the right option? https://www.inceptua.com/when-is-an-early-access-program-not-the-right-option/
- Balasubramanian, G., Morampudi, S., Chhabra, P., Gowda, A. and Zomorodi, B., 2016. An overview of Compassionate Use Programs in the European Union member states. Intractable & rare diseases Research, 5(4), pp.244-254.
- Executive Insight (2022). Initiating Warly Access Prorams: 5 Things to Consider. Available at : https://www.executiveinsight.ch/en/insights/initiating-early-access-programs-5-things-consider#:~:text=for%20taking%20part.-,Named%2DPatient%20Programs%20(NPPs),in%20the%20patient’s%20home%20country.
- Patil, S., 2016. Early access programs: benefits, challenges, and key considerations for successful implementation. Perspectives in clinical research, 7(1), p.4.