Early Access Pathways in Ukraine, Poland, and the Baltic States

Benchmarking report:

"Early and Expanded Access Pathways in Ukraine, Poland, & the Baltic States"

September 2023

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Executive Summary

This article describes pro-bono research conducted by the Eirhub team during Summer-Autumn 2023 on "Early & Expanded Access Pathways in Ukraine, Poland, and the Baltic States." The article also includes some excerpts from this study.

The final document is available for free to anyone interested or involved in the topic, including those developing internal corporate policies for such mechanisms and those responsible for developing pharmaceutical policies in Ukraine and other countries.

The work involved desk research and expert interviews with industry stakeholders: patient advocacy groups, law firms, Market Access managers of innovative pharmaceutical companies, and other industry experts.

1. The first section covers terminology, various methods for early access, disparities between access mechanisms, and their implementation in different countries.
2. In the second part, we examined early access to medicines in four Central and Eastern European countries: Poland, Ukraine, Latvia, Estonia, and Lithuania.
3. Finally, we consider the potential benefits of the early access concept to patients, patient organizations, and governments.

This document is our initial attempt to grasp the mechanisms mentioned. Therefore, we anticipate further in-depth exploration of the topic.

We invite all stakeholders to engage proactively with the mechanisms outlined in this document, foster awareness among patient communities, and leverage the opportunities it presents to Ukraine. We at Eirhub believe that a well-designed and effectively implemented early access program in Ukraine can bring numerous benefits to patients, healthcare systems, the pharmaceutical industry, and the overall well-being of the population in our country.

Our main goal is to increase awareness of the benefits of early and expanded access mechanisms for stakeholders in Ukraine, particularly patients and patient advocacy groups.  

Terminology used

Unauthorized drug—refers to a drug that has not been officially registered in a particular country. This means it has not undergone the official marketing authorization procedure or is currently in the process of undergoing the official marketing authorization procedure.

Not approved / unlicensed drug (otherwise “investigational drug” or “pre-approved drug”)— also known as an “investigational drug” or “pre-approved drug,” refers to a medication that has not been officially evaluated by a regulatory authority and has not received authorization anywhere in the world, even after successful clinical trial results.

In essence, the difference lies in their regulatory status. Unauthorized drugs have not been approved for use in a specific country, while unapproved drugs have not been authorized for use anywhere in the world.

The use of terms early access programs (EAPs) and extended access (EA) programs in this article are interchangeable in the context of Ukraine.

1. EARLY ACCESS CONCEPT

Patients who cannot be adequately treated with marketed therapies and who simultaneously are unable or ineligible to enroll in clinical trials (CTs) may seek different means of accessing unlicensed treatments. Legislators have created “expanded access” pathways to allow these patients to access unregistered medicines.

However, not every drug is eligible for EAP. To qualify for such a program, a drug needs to meet a number of eligibility criteria which vary across countries.

Figure. Conceptual Pathways to Early Access and Expanded Access Programs

However, as a whole, EAPs are intended for treatments:

1. For life-threatening conditions;
2. If there is no licensed alternative available in a given country;
3. Being under ongoing clinical trials (usually, Phase 2 and 3).

Providing supply is available and there is limited or no licensed alternative, the treating physician should be able to make a compelling case for approval. The attending physicians serve as pivotal catalysts in initiating EAPs for individual patients or patient cohorts. As delineated by the manufacturers' procedural framework, these medical professionals bear the responsibility to liaise directly with pharmaceutical manufacturers, furnish requisite patient data and clinical metrics, and orchestrate the receipt of medications for patients under EAPs.

These programs can also help to bridge the “access gap” that exists at any time during a drug’s lifecycle when there is demand, but the drug is not yet accessible either via an ongoing clinical trial or the usual prescription route for a licensed product.

The primary intent of early access programs (EAPs) is to provide treatment access when all authorized therapy options have been exhausted and proven ineffective for the patient.

Nonetheless, there is an increasing interest in simultaneously providing access whilst collecting, analyzing, and disseminating results from expanded access usage:

1. First, these data may further estimate treatment patterns and outcomes in non-trial (e.g., “real-world”) patients.
2. Second, including early access may increase statistical precision simply by increasing patient numbers—this pertains particularly to expanded access use of rare disease drugs.

Also, so far, opinions differ to what extent data collection under expanded access is feasible, desirable, and reliable. For example, data from expanded access are incorporated by health technology assessment (HTA) bodies to determine the cost-effectiveness of novel therapies in the UK, the Netherlands, the USA, and France. At the same time, to what degree data from expanded access to investigational medicine are published in academic literature remains unknown.

Consequently, differentiating between clinical trials and EAPs is crucial. Clinical trials are primarily designed to gather data, via rigorous scientific investigation, on the efficacy of a novel drug in managing a particular condition, its potential side effects, and the associated risks to human health. On the other hand, EAPs serve to grant patients with severe and critical ailments access to pharmaceuticals that have not secured official licensure or authorization.

Another major issue of concern for pharmaceutical companies is that the regulations regarding EAPs are not the same all over the world.

EAPs & Clinical Trials

CTs are the channel through which patients access investigational or otherwise unapproved medicines. However, there are patients with serious or life-threatening diseases for whom enrollment in a trial is impossible, and all comparable and available treatment options have been exhausted.

Also, while a CT is protocol-driven, and historically it was the only way for patients in many countries to obtain preapproved drugs, and it is where the research is the primary intent of using an investigational drug. On the contrary, in an EAP, the core intent is treatment. People enrolled in CTs correspond to specific biomedical criteria, and people who should not be enrolled in a clinical trial are also defined (so-called exclusion criteria).

Moreover, an EAP is also managed completely differently from a CT, both in terms of documentation and approval process, and typical clinical activities like monitoring are not usually performed. However, safety data collection and reporting are generally required.

In the subsequent sections of this report, we will delve into a comprehensive examination of global mechanisms available under the umbrella of a) early access programs:

1. Open-Label Extension study (OLE).
2. Compassionate Use Programs (CUPs).
3. Named-patient Programs (NPPs).

b) expanded access:

1. Off-label use.

Open-Label Extension (OLE) study

The term "post-trial" access is the provision of investigational medications to a CT participant after successfully completing an interventional CT, both for Phase 2 or 3. A pharma company may consider this when the trial has met its objective of collecting efficacy or safety information needed to support registration. A pivotal CT is often double-blind, and patients requiring treatment for a prolonged interval beyond the end of the CT are offered an open-label extension (OLE) study.

Many pharma companies implement OLE trials to ensure continued access to the study drug to patients who might have benefited from the investigational drug during participation in a CT until regulators approve the investigational drug and it is commercially available in the specified country.

Off-label use concept

In some countries, off-label drug use is considered an expanded or compassionate use. Conceptually, a drug used off-label is, by definition, a drug used differently than the authorized one. For example, a drug can be given for a different disease or at an extra dose than indicated on the label. Thus, off-label use only applies to drugs that are already authorized.

Compassionate Use basis

Compassionate use only applies to drugs not yet authorized for any condition.

A medicinal product given on a compassionate basis is, first and foremost, a treatment. It is a medicinal product not yet thoroughly evaluated, prescribed to treat people with no other therapeutic options. Running a Compassionate Use Program (CUP) consists of making a medicinal product available for compassionate reasons to a group of patients (or sometimes individual patients on a case-by-case basis) with a chronically or seriously debilitating disease or whose disease is considered to be life-threatening, and who cannot be treated satisfactorily by an authorized medicinal product. 

Even though it is not entirely sure whether the patient's treatment on a compassionate use basis is proper, if there is no other option and there is the slightest chance that the product will be effective, the patient should benefit from it.

Named-Patient basis access

Named-patient basis access is the supply of unauthorized drugs for individual patients in response to requests by doctors on behalf of specific or "named" patients. It is limited to the requested named patient or patients only. Unlike CUPs, Named-Patient Programs (NPPs) are entirely initiated by doctors, addressing their request directly to the company to treat an individual patient under the doctor's direct responsibility.

Figure. Mechanisms of Early and Expanded Access Programs on the Pharmaceutical Product Life-Cycle Timeline

2. DEFINITION OF EARLY ACCESS PROGRAMS IN EUROPE

Access to unauthorized treatments in Europe can be achieved through participation in CTs or through early access.

The EU pharmaceutical legislation envisages several options enabling early access to necessary medicines that are eligible for centralized marketing authorization procedure by the European Medicines Agency (EMA): 

• accelerated assessment of application due to major public health interest and, in particular, from the viewpoint of therapeutic innovation;
• conditional marketing authorization for medicines before complete data are available;
• compassionate use programs (CUPs) for unauthorized medicine for patients with an unmet medical need;
• named patient basis access, or named patient programs (NPPs), for unauthorized medicines for individual patients in response to requests by doctors on behalf of specific, or “named”, patients;
• EU Expanded access programs are intended for patients who have been treated in a clinical trial and who wish to continue the treatment.

Compassionate Use Programs (CUPs)

According to the definition stipulated in Article 83 of Regulation (EC) No 726/2004, programs initiated under compassionate reasons, or CUPs, make a medicinal product belonging to the categories of: 

• the medicinal product contains a new active substance that has not been authorized in the EU until 20 May 2004;
• medicinal product has a proven significant therapeutic, scientific, or technical innovation or that the granting of authorization in accordance with this Regulation is in the interests of patients or animal health at the Community level, available for compassionate reasons to a group of patients with a chronically or seriously debilitating disease or whose disease is considered to be life-threatening, and who cannot be treated satisfactorily by an authorized medicinal product. The medicinal product concerned must either be the subject of an application for a centralized marketing authorization or must be undergoing clinical trials.

Named-Patient Programs (NPPs)

NPPs are the supply of unauthorized medicines (or authorized medicines from a different country) for individual patients in response to requests by doctors on behalf of specific, or “named”, patients with a chronically or seriously debilitating disease, or a life-threatening disease, and who cannot be treated satisfactorily by an authorized medicine and is limited to the requested named patient or patients only.

3. THE CONCEPT OF EXPANDED ACCESS IN UKRAINE

Long before the official endorsement of EAPs in Ukraine, pharmaceutical companies predominantly provided Ukrainian patients with debilitating and life-threatening conditions and orphan diseases with innovative drugs free of charge by using humanitarian aid leverage. Rare disease drugs were supplied on an individual basis.

By doing so, pharmaceutical manufacturers paved their way by elaborating prescription habits in physicians and studying patient populations for the following commercialization through public centralized purchases of drugs.

However, expanded and early access policies needed to be better regulated, which, in turn, significantly hampered the physicians' medical practice by creating prosecution risks for prescribing medicines off-label or those not mentioned in the official approved national clinical guidelines.

The existing regulatory vacuum casts a shadow over the legality of free donation of drugs from the companies as drugs were administered solely under the patient's responsibility and without proper monitoring of clinical outcomes.

Eventually, immediately before the beginning of Russia’s unprovoked invasion of Ukraine in Feb 2022, the Ukrainian Parliament passed Law No. 2054-IX, introducing the concept of the compassionate use of medicines owing to the significant impact of local patient advocacy groups and industry representatives. 

Due to the full-scale invasion of Russia of Ukraine on Feb 24, 2022, many severely ill patients in the country received critically needed therapy with innovative drugs coming to Ukraine as humanitarian aid/donations.

For the sake of terminology clarity, the introduced compassionate use policy in Ukraine does not correlate with an understanding of the compassionate use legal mechanism by EMA. Ukrainian provisions for compassionate use of medicines were bound to embed all existing mechanisms for early access to drugs: off-label, OLE, CUPs, and NPPs.

Figure. Available Mechanisms of Early and Expanded Access in Ukraine

These are introduced regardless of the cohort/ individual division—at any stage of development under the domestically devised and applied umbrella conception of "medicines for compassionate use" to provide patients with debilitating and life-threatening diseases with an official reason to access any therapy whether authorized by FDA/EMA or not. The CUPs in Ukraine imply two types of programs:

1. Post-trial access to an investigational drug following the completion of a clinical trial (in the interests of continuing therapy).
2. Expanded and early access use covers unauthorized, off-label, or medicines not envisioned in the clinical guidelines, medicines at Phase II or III of clinical trials (traditional CUPs), and other compassionate use cases.

Figure. Benefits of Early & Expanded Access Programs for Ukraine

The "Early & Expanded Access in Ukraine, Poland, & the Baltic States" document is a must-read for a comprehensive understanding of the early and expanded access mechanisms currently implemented in Ukraine. It features a list of programs that various manufacturers in Ukraine have implemented to date for different indications.

Download for free to learn more:

Recommendations for Stakeholders on Early Access Programs in Ukraine

Early access programs are a relatively new instrument currently gaining momentum in the world. It is essential for countries that are new to using early access mechanisms to study successful examples of their application and implement them in close cooperation with patient communities. This is due to the ambiguity surrounding early access programs regulation, terminology, and general concepts.

Figure. Recommendations for Stakeholders on Early Access Programs in Ukraine

For patients & their families:

• Ask your physician about the possibility of benefiting from mechanisms for obtaining authorized and unauthorized medicines in the country.
• Ask your physician about possibly participating in Compassionate Use Programs as part of a patient cohort or individually according to your needs.
• Inquire about the experience of the members of your patient community in participating in early access programs.
• If you know the product's manufacturer, contact their representative through the patient community or directly inquire about drug availability from distributors. (If the medicine you need is not authorized in the country, then ask the representative about the availability of compassionate use programs.)

For Patient Advocacy Groups (PAGs):

• Clearly define a list of conditions and inclusion criteria with adherence to which patients of your community, along with physicians, can attempt to apply for CUPs.
• Develop expertise and strategies for documenting and providing a clinical rationale for medicine tailored to each patient in your community in collaboration with the medical community.
• Proactively raise awareness and develop skills among physicians interested in participating in early access programs and filling out the necessary forms for patients on the drug manufacturer's website.
• Regularly monitor and promptly inform patients and physicians about new available compassionate use programs.

For Physicians:

• Closely collaborate with friendly PAGs about their awareness of CUPs for medicines and solicit the necessary support.
• Keep track of manufacturers of innovative medicines, CT platforms, and other venues to learn about new treatments and find compassionate use options for your patients.
• Regularly scan with drug manufacturers for available CUPs for your patients' needs. Inquire about policies and application requirements on their official website.
• Ask your colleagues and peers about their personal experiences with CUPs.

For Manufacturers:

• Proactively educate patient advocacy groups and the medical community about available CUPs.
• Host educational webinars on the CUP application process.
• Consult your logistics/distribution partner about delivering medicines to Ukraine through the CUPs.
• Prepare a list of frequently asked questions (FAQs) and answers for patients, doctors, and patient advocacy groups (PAGs) regarding the application process and program participation in collaboration with the parent office.
• Prognose the potential volume of possible requests for participation in the program.

For the Government:

• Study the examples of the most relevant countries for Ukraine with successful experience in implementing EAP, especially CUP national policies.
• Scan for opportunities to simplify all necessary procedures for patients and doctors to participate in such programs.
• Consider introducing financing options for early access programs in Ukraine from other sources (i.e., charity funds, patient groups, etc.) rather than exclusively at the expense of the drug sponsor.
• Establish a data collection system on the efficacy and safety of medications used under CUPs.
• Explore all possible tools to improve the awareness of patients, PAGs, and doctors about the possibility of their participation in programs of access medicines under CUPs because this is an additional and non-burdensome mechanism for improving access to expensive and innovative drugs in UKR.

CONCLUSION

Ensuring patient access to medicines is a global challenge. It's not just about developing new drugs but also making sure they are accessible and affordable to those who need them.

Amidst a growing number of biopharma companies, the expansion of R&D, and the increasing emphasis on corporate social responsibility, strategies and approaches to expand, improve, or accelerate patient access to medicines are gaining momentum.

This is especially relevant and essential for patients suffering from life-threatening and debilitating diseases who are unable to participate in CTs for various reasons or those for whom the benefits of drugs are likely to outweigh the potential risks.

Historically, developed countries have led the way in adopting EAP approaches. Nevertheless, developing countries may succeed in expanding and accelerating access to medicines for their populations today owing to the internal policies of drug manufacturers, the proactivity and persistence of PAGs, and the willingness of physicians to participate in such programs.

In reality, every stakeholder in this complex system has the potential to make a significant impact and help improve patient access to life-saving medicines.

About Eirhub

Eirhub is a professional consulting firm providing advisory services for Life Sciences industries stakeholders—Pharmaceuticals, MedTech, Digital Health, and Healthcare.

We support various industry stakeholders on market access topics, regulatory environment assessment, market analysis and intelligence, executive search, recruitment, and talent mapping.

Regions we cover CEE, Ukraine MENA, South Caucasus, and Central Asia.

Our Ukrainian roots inspire us to help rebuild Ukraine and its economy to bring new businesses and knowledge into our country.

How Eirhub can help in implementing EAPs in Ukraine.

These services are crucial for pharmaceutical companies to navigate early access and compassionate use programs in Ukraine effectively. Here's what Eirhub may be valuable at:

• Comprehensive Regulatory Analysis. Eirhub can conduct a thorough analysis of the regulatory framework governing early and extended access programs in Ukraine. This includes reviewing existing regulations, guidelines, and requirements to ensure compliance.
• Analytical Report on Target Indications. Our team can prepare an analytical report focused on the target patient populations for specific indications. This report would include information on disease prevalence, demographics, and unmet medical needs.
• Competitive Treatment Options Analysis. We can provide a detailed analysis of registered competitive treatment options in Ukraine. This includes assessing the efficacy, safety, and pricing of these treatments.
• Price Parameter Analysis. Analyzing the price parameters of available treatment methods in Ukraine is essential to understanding the economic aspects of early access programs. Eirhub can provide this information and, that in turn, can be valuable for pricing and reimbursement strategies.
• Stakeholder Mapping. Identifying and mapping all relevant stakeholders involved in early access programs, including regulatory authorities, ethics committees, patient advocacy groups, healthcare providers, and pharmaceutical companies.
• Recommendations and Communication Plan. Formulating recommendations for decision-making participants, such as pharmaceutical companies, and developing a comprehensive communication plan. This plan should address the needs and expectations of each stakeholder group.
• Identifying Target Healthcare Infrastructure and HCPs. Identifying healthcare institutions and treating physicians willing to participate in early access programs for specific indications. Assessing their readiness and willingness to collaborate is crucial for program success.

If you have any questions or requests regarding early access programs in Ukraine, Poland, or the Baltic States, write Yevgen Brovko or Anastasiia Havrysh directly.