By John Lagus, founder of Bluestem Pharma Consulting, LLC

In my current role as a consultant focused on early access programmes (EAPs), one stakeholder I regularly engage with is rare disease patient groups. I am currently working with a patient group where there is a pharmaceutical company developing new medicine for the rare disease this patient group supports. Excitingly, clinical trials are ongoing, but the patient group has learned many patients do not meet the strict inclusion and exclusion criteria used to qualify for a trial.

Not surprisingly, patients and caregivers are desperate to understand when their child may get access to this medicine. This article will explain some of the factors and development milestones that influence when a pharmaceutical company will make their medicine available via early access, particularly for an orphan drug used to treat a rare disease.

What is an EAP?

Most countries in the world have legislation in place allowing patients with serious or life-threatening conditions to get access to medicines that cannot be obtained via normal commercial channels. If the medicine is still being developed and tested, some patients may not be able to join a clinical trial because they do not meet the entry criteria or don’t live close enough to a hospital where the trial is being run. In some cases, patients live in a country where this new medicine won’t be launched for several years or possibly not at all. In either scenario, time is of the essence and for some patients waiting too long may mean the difference between life and death.

This type of access may locally be called compassionate use, expanded access, special access, or named patient supply. An EAP is a formal mechanism put in place by a pharmaceutical company utilising the various legislations to facilitate access to these medicines in a controlled way. An EAP will likely still have inclusion and exclusion criteria like a clinical trial, so all patients with a specific disease may not qualify—access is not automatically guaranteed for all, but it can be an important mechanism for improving access where regulatory and geographics barriers exist.

Today, companies typically post a policy on their website to confirm if they are providing the medicine via early access which will include information on how they evaluate requests for early access. For medicines early in development this statement may simply say early or expanded access is not being offered while clinical trials are ongoing. However, as more data is gathered from clinical trials, there is often increasing willingness to allow early access, particularly for orphan drugs used to treat rare diseases.

Over the past 19 years I have worked with biotech and pharmaceutical companies to design and implement hundreds of global EAPs. The companies implementing these programmes span in size from large multinational pharmaceutical giants to small virtual biotech companies.

Most pharmaceutical companies, regardless of their geography, will first target the United States (US) market for registration and commercialisation because it is the largest and most lucrative country for selling medicines. Companies often stage their global EAP to start in the US with an expanded access programme and then consider countries outside the US later in the development process or even after FDA approval.

There are many factors influencing when a pharma makes their medicine available via early access. Some of these include the severity and impact of the rare disease being treated, the stage of the drug development, the size of the pharmaceutical company, and where they intend to commercialise.

Benefit-risk assessment in early access

Universally, companies of all sizes focus on getting their medicine through regulatory processes to gain approval so the largest number of patients can ultimately gain access. They run clinical trials to generate data demonstrating the safety and efficacy of medicines. The more data generated, the better they understand the benefits and risks associated with the use of any given medicine for individual patients and groups of patients.

Benefits means there is some positive effect of the medicine like a cure or more often, a lessening of symptoms for the disease being studied. Risks include adverse events or even death. The benefit-risk profile of a medicine will evolve over time as more data from clinical trials are collected and compiled.

In the pharmaceutical industry, this concept of benefits and risks are formally assessed both by companies and regulators to make informed judgement whether the benefits of a new medication outweigh the risks. A benefit-risk assessment for early access is influenced by the severity and impact of the rare disease intended for treatment, the benefits and risks of other available medicines for the condition, and a determination of what can be done to prevent or monitor any risks.

I bring this up because with respect to any request for early access from a physician on behalf of a patient, both the pharmaceutical company and the regulatory agency take a medicine’s benefit-risk profile into consideration. In an EAP the pharmaceutical company provides information to the patient’s physician about the potential risks and benefits of using the medicine. The patient’s physician should share this information with the patient or the patient’s caregiver. It’s important that patients and their loved ones understand both the potential benefits and risks associated with the use of this medicine so they can decide whether to proceed with its use.

Early access during clinical trials

Early access to medicine during clinical trials would be for patients who cannot enroll into existing clinical trials because they do not meet the strict inclusion and exclusion criteria for the trial. Given likely uncertainties in the benefit-risk assessment, companies would typically only consider offering medicine at this stage for diseases without any meaningful treatment, and for which the patient could have significant health consequences or even death.  

Few pharmaceutical companies will initiate early access at this stage. Smaller companies may have less ability to do so based on the factors they are dealing with including limited financial resources, smaller staff numbers with limited bandwidth to review and manage these requests, or the company may have only manufactured enough drug supply for their clinical trials. Larger companies can manage some of the factors better because of their size, so they may be more likely to allow early access during clinical trials.

Early access after the pivotal clinical trials are fully enrolled

Once the trials are fully enrolled, newly diagnosed patients who meet the inclusion and exclusion criteria can no longer enroll in the trials. The pharmaceutical company may open broader early access to the medicine at this stage. The company may choose to allow access at hospitals that participated as a site in the clinical trial or may wish to only enroll patients who continue to fit the inclusion and exclusion criteria from the trials. Guidelines on the above will be set by the company.

Early access after final data readout from pivotal clinical trials

If the pharmaceutical company has met its endpoints in the clinical trial and believe they have a medicine that will be approved by the US FDA and other agencies, this is the most likely point a company will open an expanded access programme in the United States. Companies of all sizes typically open programmes at this stage to include patients who fall outside the inclusion and exclusion criteria used in the clinical trials. Smaller companies may still be unable to open a programme at this stage if this product is the first medicine that will be commercialised, and they have limited funding available.

Large companies with plans to register the medicine in Europe will consider expanding the EAP to include key countries where they expect to launch commercially following regulatory approval.

Early access after FDA approval

At this stage, the focus is providing the approved medicine via early access outside the US. A small percentage of companies will wait until after FDA approval to make their medicine available via early access for the first time. These companies tend to be smaller, have no revenue from other commercialised products, and cannot afford to initiate an EAP sooner. Large companies may expand their global EAP to include even more countries.

Conclusion

The ability and appetite to operate an EAP varies from company to company, Therefore, unfortunately, there are no singular answer about when a company will start an EAP. It may come down to the nature of the rare disease being treated, the size of the company, the benefit-risk profile, or even the comfort level of senior leadership or investors in a pharmaceutical company with the idea of early access.

Given this reality, it is important patient groups understand how clinical trials work, as well as understanding the basics about EAPs. Patient groups can be instrumental in communicating with pharmaceutical companies to better understand the factors influencing the company’s thinking about if and when early access may be implemented. Once an EAP is put in place, patient groups play an important role educating and managing expectations of patients and families they serve—making their role pivotal.

About John Lagus

John is the founder of Bluestem Pharma Consulting, LLC, helping patients around the world access medicines to treat serious or life-threatening diseases. John works with pharma and biotech companies to better understand and implement best practices for global early access and expanded access programmes that meet a patient’s unique medical needs.

Early in his career, John was introduced to the orphan drug and rare disease space, when he joined Orphan Medical. Early access strategies were utilised to supply several of the company’s FDA-approved medicines to patients outside the US.

Over the years, John has had extensive experience with the design, set-up and implementation of more than 200 global early access programmes. John also provides help to patient groups and those they serve. Supporting the rare disease community continues to be his passion.

Contact John at john@bluestempc.com, visit his website bluestempc.com, or connect with him on LinkedIn.

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