Clinical Researcher—April 2025 (Volume 39, Issue 2)

PRESCRIPTIONS FOR BUSINESS

Dea Belazi

 

 

 

Hope is often the driving force behind the relentless work of research teams dedicated to developing transformative therapies for the millions of individuals and families impacted by rare diseases. Through collaboration with manufacturers, patients, advocates, and clinicians, these researchers are advancing promising therapies into clinical trials and pioneering innovative tools and technologies that offer hope to the 300 million people worldwide living with a rare disease—95% of whom still lack effective treatment options.

The introduction of specialty pharmaceuticals and cell and gene therapies (CGTs) has brought newfound optimism, with the potential to slow disease progression or even cure these conditions. However, the high costs, limited distribution, and complex reimbursement structures surrounding these therapies limit availability and access.

These challenges delay treatment, exacerbate patient suffering and uncertainty, contribute to worse health outcomes, and drive up healthcare costs. For many, financial barriers make these life-saving treatments unattainable. Overcoming these obstacles will require a collaborative effort from researchers, policymakers, and industry leaders.

Identifying Roadblocks and Proposing Solutions for CGT Scalability

Scalability Challenges

The production of CGTs at scale presents significant challenges due to their complex, personalized, and time-intensive manufacturing processes. The limited number of decentralized production facilities exacerbates these challenges, delaying the time it takes to bring new therapies to market. Additionally, the high costs associated with small-batch production create financial barriers that further hinder access.

To address these issues, advanced automation and data analytics can streamline manufacturing processes, improving both efficiency and scalability. Establishing decentralized production hubs can also facilitate quicker, localized access, accelerating the availability of these therapies. Furthermore, optimizing production methods and fostering early collaboration with regulatory agencies can further enhance efficiency, reducing delays in product launch, market access, and distribution.

Addressing the High Cost of Therapies: Solutions for Improved Access and Affordability

The high cost of CGTs poses significant challenges with payer coverage and decision-making, creating notable disparities in access to treatment. For patients, the financial burden can be overwhelming. A recent survey revealed that 61% of individuals with commercial insurance feel stressed about their healthcare costs, with 48% reporting rising out-of-pocket expenses year-over-year. As a result, the affordability of life-saving treatments remains a pressing issue.

On average, rare disease patients incur annual healthcare costs of $266,000—10 times higher than those with common diseases, whose average annual costs are $26,000. CGTs, which can exceed $1 million per dose, are particularly expensive. For ultra-rare diseases that affect fewer than 100 people globally, the inability to achieve economies of scale drives costs even higher. For instance, the therapy for Metachromatic Leukodystrophy costs $4.25 million, making it the world’s most expensive drug.

Out-of-pocket expenses contribute significantly to the high rates of drug abandonment. Prescription drug affordability review boards, which evaluate drug costs based on quality-adjusted life years, may impose cost restrictions that limit access. Research shows that when cost-sharing exceeds $100, drug abandonment rates can range from 32% to 75%.

To make CGTs more accessible and financially sustainable, aligning treatment costs with outcomes through value-based contracts and outcomes-based pricing is key. Capping out-of-pocket expenses can improve adherence, with studies indicating that a $0 copay threshold increases treatment initiation rates by up to 70%. Additionally, stop-loss insurance and payer cost-sharing adjustments can alleviate financial strain on both patients and insurers.

Payers can utilize specific stop-loss coverage to mitigate the impact of individual high-cost claims or opt for aggregate stop-loss protection to avoid excessive financial exposure from a high volume of costly cases.

Overcoming Regulatory Approval Delays

U.S. Food and Drug Administration (FDA) approval pathways for CGTs are complex and continuously evolving, often leading to delays. In the United States, standard regulatory review takes around 10 months, though therapies offering significant improvements in safety or effectiveness can qualify for Priority Review, shortening the process to six months. However, the lack of historical precedent for CGTs adds another layer of uncertainty, complicating the approval process.

Incorporating real-world evidence (RWE) alongside traditional clinical trial data can accelerate approvals by providing additional insights into a therapy’s effectiveness and safety in everyday settings. RWE helps regulators make informed decisions, especially for rare and complex diseases.

Collaboration led by the American Society of Gene and Cell Therapy (ASGCT) helps bridge the gap between researchers, industry leaders, and regulatory bodies, ensuring that RWE is effectively collected, standardized, and integrated, leading to a more streamlined and transparent approval process.

Expanding policy initiatives to establish clear frameworks for RWE use will further reduce uncertainty and support quicker access to innovative therapies.

Challenges in Recruiting Rare Disease Patients for Clinical Trials

Ultra-rare diseases have limited patient pools, making recruitment a significant challenge. Geographic barriers, invasive procedures, and a lack of awareness often discourage participation, while concerns about potential side effects also affect enrollment rates.

Artificial intelligence–driven patient matching can streamline recruitment by efficiently identifying eligible participants, helping trials progress more quickly. Decentralized trials and remote monitoring enhance accessibility, allowing patients to participate from various locations and reducing travel and logistical burdens.

Patient advocacy groups (PAGs) play a vital role in educating and supporting patients throughout the enrollment process. By amplifying the patient voice and fostering communication between patients, healthcare providers, and manufacturers, PAGs help bridge gaps in understanding and access. They also provide actionable insights to pharmaceutical companies, ensuring treatment development aligns with real-world needs and priorities.

Addressing Delivery and Administration Barriers

A limited number of FDA-approved treatment sites delays patient access, while specialized storage and handling requirements add logistical challenges to product distribution. Advancements in cold chain logistics and decentralized distribution models have helped streamline the storage and transportation of temperature-sensitive therapies, improving overall drug delivery efficiency.

Limited distribution networks (LDNs) established by pharmaceutical manufacturers to manage the distribution of high-cost or complex therapies, often exclude health-system specialty pharmacies (HSSPs), further impeding access and increasing wait times. On average, patients face a six-day wait for limited distribution drugs (LDDs), compared to just three days for non-LDDs.

Expanding specialty pharmacy networks can significantly improve access by increasing the availability of specialized medications. Integrating HSSPs into the distribution process helps reduce delays, ensuring patients receive timely treatment.

Navigating Complex Reimbursement Processes and Prior Authorization Barriers

Restrictive payer policies often result in long delays in patient access to treatment. For instance, co-pay accumulator programs, which exclude manufacturer coupons or assistance payments from counting toward a patient’s deductible or out-of-pocket maximum, can leave patients responsible for the full cost once assistance runs out. This disproportionately affects individuals with rare diseases who often rely on high-cost treatments. Additionally, varying and complex prior authorization policies in health plans create further obstacles, limiting patients’ ability to receive timely care.

While patient assistance programs provide essential financial relief, some insurers argue that they drive up healthcare costs by undermining cost-sharing mechanisms intended to curb unnecessary spending. However, organizations like the Patient Access Network Foundation highlight that these programs are vital for patients who might otherwise be unable to afford life-saving treatments.

Expanding coverage exceptions for FDA-approved gene therapies helps improve affordability, allowing more patients to benefit from these transformative treatments. Strong advocacy for standardized reimbursement pathways is also crucial in fostering a more equitable healthcare system, reducing financial barriers, and ensuring all eligible patients have access to the therapies they need.

The Path Forward: Advancing Access to Rare Disease Treatments

Breaking down access barriers requires ongoing collaboration among clinical researchers, industry leaders and policymakers. Grant funding and nonprofit research initiatives are crucial for driving innovation, while PAGs play a key role in research, policy advocacy and support patients directly.

Investing in innovation is essential to improving access to rare disease treatments. By prioritizing accessibility and affordability, all stakeholders can ensure that every patient has the opportunity to benefit from these life-changing therapies.

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Dea Belazi is CEO of AscellaHealth.