In recent years, a growing number of pharmaceutical companies have recognized the potential benefits of pre-launch access programs, either as components of later-stage clinical development or early access programs or to support importation of drugs into countries recognizing an FDA or European Medicines Agency (EMA) approval. These programs help patients access investigational therapies prior to regulatory approval or commercial launch and are generally reserved for therapies that have demonstrated an acceptable level of proof of concept and safety. In addition to expanding treatment options for patients, often in indications that have limited or no approved therapies available, pre-launch access programs are also widely seen to play a significant role in advancing many drug development programs.

In many cases, pre-launch access programs can be structured to provide additional safety and efficacy data that can support regulatory requirements. They can increase awareness of both a disease and progress in research among patients and clinicians and can highlight and reinforce a company’s commitment to patients. In some cases, early access or import programs can generate early revenue and help companies gain a foothold in a target market before approval, positioning therapies for broader uptake among both clinicians and patients after commercial launch.

Nonetheless, pre-launch access programs can also present several challenges and potential risks, including expanded reports of adverse events (AEs), treatment in patient populations that do not reflect clinical research populations, efficacy results that differ from prior clinical data, and higher-than-expected costs to implement and maintain the program. It is important that companies carefully assess both the potential benefits and risks associated with pre-launch access programs to determine the best structure to optimize benefit. Case studies may be useful to identify best practices related to timing, monitoring, and other factors.

Identifying The Challenges

Many challenges associated with pre-launch access programs are universal, but others depend on factors such as the target market. In most cases, a primary concern is the impact of AEs reported among patients participating in a pre-launch access program. Even in cases where a range of AEs seen in prior clinical research are anticipated, these events can have a negative impact on perceptions of both a drug development program and a company and may cause delays in the regulatory review process. Concern about AEs can reach and influence all stakeholders, including patients, clinicians, advocacy groups, regulators, and investors. These risks are most often associated with more severe AEs, including unexpected death, long-term damage or complications, and events that affect pregnant or pediatric patients.

Another concern with pre-launch access programs is that the experiences of enrolled patients can create misperceptions about a drug among clinicians or future patients. This is often a risk when participants in a program have a different profile than patients who participate in clinical research. For example, while participants in clinical research might include patients with moderate forms of a disease, an early access program might be restricted to patients with a higher unmet need or in later treatment lines. As a result, data related to safety and efficacy among participants in that program can differ compared to results from clinical research. The differences in treatment populations can influence clinicians’ perspectives on the profile of patients who are appropriate for treatment with a therapy after approval and might also impact payer decisions regarding which patients should be eligible for reimbursement after launch.

Another important consideration is that pre-launch access programs for single-dose or other curative therapies can potentially reduce the pool of patients appropriate for treatment with a product once launched. This is especially concerning for companies developing single-dose treatments for diseases and disorders that impact very small patient populations. Costs to plan, execute, and maintain these programs can also be higher than expected if the treatment needs to be provided free of charge for a longer period than planned due to delayed approval or commercial launch. Companies also should be aware that aggressive promotion of pre-launch programs may be prohibited and could negatively impact the opinions of regulators, who might view such efforts as unethical in cases where available safety and efficacy data is limited.

Planning for pre-launch access programs now also often requires collaboration among a range of internal stakeholders, including medical, commercial, regulatory, market access, legal and compliance, and production and supply chain teams on a global scale, as well as regional launch managers and country launch teams with the local expertise necessary to align on optimal strategies. Insights from the production and supply team, potentially including third-party manufacturers, can be essential to ensure adequate product supply for all needs, and these discussions should reflect anticipated timelines and challenges in expansion of manufacturing capacity. Commercial teams can help ensure program structures reflect the target market, and medical teams can provide important perspectives regarding patient compliance and safety considerations.

Developing Strategies To Minimize Risk

In order to ensure successful development and implementation of pre-launch access programs, companies need to consider a range of factors and take steps to mitigate risk. In most cases it will be advantageous to start planning for these programs early in the drug development process — in some cases as early as Phase 1 research. This can better position companies to align on optimal strategies both internally and with external stakeholders and to secure all required regulatory approvals. Early planning can also help companies be better prepared to reallocate resources as needed to prevent any delays in clinical research and regulatory review. Once a pre-launch access program is in place, companies should be prepared to refine the program as clinical development advances, continually optimizing approaches as more information becomes available.

To plan for any challenges regarding AEs, drug developers must also provide clear guidance to clinicians related to AE risk and label restrictions. Protocols may require participating healthcare providers (HCPs) to conduct pre-treatment screenings and in-treatment monitoring of patients. Companies must also ensure HCPs understand the necessary guidelines and procedures for reporting AEs both to regulatory contacts and to the company. Upon receipt of information related to any AEs, companies should have in place a turnkey process for communications targeting HCPs, patients, investors, and other stakeholders.

Clear and efficient processes in monitoring pre-launch access programs must be established early and properly maintained at every stage. This should include, at a minimum, a dedicated tracking system to monitor patient screening and enrollment, the number of treatment centers and HCPs participating in the program, generated revenue, and timelines for program duration, expansion, or contraction. There must also be a clear plan for program termination or transition at commercial stage. Finally, processes for communication to HCPs and patients participating in pre-launch access programs should be established early and positioned to address any issues rapidly and effectively.

Are your oversight procedures in place?

Recent updates to ICH GCP E6 recognize the increase in remote clinical trials and outlines expectations for Investigator Oversight. Check out Sandra “SAM” Sather’s webinar, “Investigator Oversight Plans: Essentials for Inspection Readiness Post ICH GCP E6 (R2) Addendum

Building On Best Practices In Pre-Launch Access Programs

Broad consensus on the benefits of pre-launch access programs indicates these programs are likely to be considered for a wider range of investigational therapies in the years ahead. Increasingly, companies will have to invest early in the expertise and services necessary to plan and execute these programs successfully. These efforts should outline the potential risks and benefits of different program structures, which can vary widely for different therapies. Planning should address the impact of pre-launch access programs on all stakeholders, including HCPs, patients, advocacy leaders, investors, and media. Planning also should outline the potential impact on commercial success of a therapy. Early and careful planning is both effective and now often essential in mitigating risk and maximizing benefit while also ensuring pre-launch access programs reach their intended goal in supporting access to treatment for appropriate patients.

About The Author:

Lorenzo D’Angelo, Ph.D. is an associate principal in the life sciences practice at Charles River Associates (CRA). He has more than six years of experience in collaborative scientific and industrial research in the areas of medical technology and e-health and more than four years of experience in life sciences consulting. Using his experience in research, project management, and analytical and statistical methodologies, he focuses on market entry, growth, and launch strategy. Dr. D’Angelo has conducted and supervised projects providing clients with qualitative and quantitative market insights, operational launch support, market access organizational design, salesforce optimization, and portfolio contracting strategies across Europe, the U.S., Latin America, and beyond.

The views expressed herein are the author’s and not those of CRA or any organizations with which the author is affiliated

Leave a Reply