Key Challenges with Orphan Drug Development for Rare Disease Treatments

By Lisa Jenkins VanLuvanee, Ph.D.

Per the US FDA, orphan drugs address rare diseases affecting fewer than 200,000 people in the United States. Developing these therapies presents challenges beyond typical drug development. The Orphan Drug Act offers incentives such as market exclusivity and tax credits to encourage development. However, securing orphan designation is just one step in a complex process that requires a clear understanding of unique scientific, clinical, regulatory, and asset valuation hurdles.

Don’t risk limiting your success by relying solely on experts who focus only on orphan designation requests. Success in orphan drug development relies on overcoming challenges throughout development and the US marketplace.

Outdated approaches and limited strategies can jeopardize your product’s potential. Instead, rely on regulatory and development experts who see securing an orphan designation as just one aspect of developing an orphan product. At Facet, we believe the true value of your asset is driven by your strategic development of that asset and your preparedness for the US market once approved. Securing orphan designation is just one component of this activity.

Hidden Complexities in Orphan Drug Designation and Development

Orphan drug development comes with special and unique (some might argue, hidden) challenges that are likely to slow development if not properly addressed. Often, there are few or no limited animal models of disease available making it difficult to design safe early phase clinical trials

• Manufacturing costs can be high since orphan products are typically produced in smaller batches and may require specialized processing techniques.
• Patient recruitment is challenging due to the limited number of individuals with the orphan disease. Sponsors may encounter fierce competition for patients. When multiple companies are pursuing development for the same patient population. In some cases, clinical protocols rule out the use of other investigational products, making some patients ineligible to participate in more than one clinical trial, thereby further reducing the eligible patient population for study.
• Patients and caregivers often must travel great distances to participate in clinical studies.
• Per-patient clinical trial costs tend to be significantly higher than those for non-orphan studies.
• Few physicians may have expertise in the orphan disease being studied, and educational efforts to diagnose and treat patients under a clinical protocol may be necessary.
• Securing funding can be difficult because of the perceived lower return on investment, especially given the high costs of development.

US Regulatory Pathways for Orphan Drug Development Require Flexibility and Education

There are often regulatory hurdles to overcome as well. While typically touted as an advantage, FDA has (and usually does) exercise regulatory discretion when reviewing and approving products to treat orphan indications. The evaluation process for orphan drug designation requires a clear scientific rationale, and applicants may benefit from seeking scientific advice or scientific advice specific from regulatory agencies to address unique development needs and regulatory requirements. Although this is a certain benefit, the regulatory pathway can be unclear.

• Selecting efficacy outcome measures that are appropriate from a treatment and standard of care perspective that also satisfy regulators can be particularly challenging. This sometimes requires establishing new outcome measures and preparing full validation packages for them.
• For any product developed for a rare disease, key questions include: What amount of efficacy data is needed to demonstrate a therapeutic effect? What level of exposure is required to demonstrate product safety? How many studies are necessary? What is the optimal trial design? The answers to these questions have proven to be disease- indication and product-specific.
• There may be few, if any, regulators who are experts in the rare disease indication. Educational efforts may be necessary to bring health authorities up to speed on the disease state, what factors are important to patients in the treatment of the rare disease, and possibly varying benefit/risk assessments between patients, physicians and regulators.

Market and Asset Value Challenges with Orphan Drug Product Development

From an asset value standpoint, market considerations are also different when it comes to orphan product development, launch, and marketing.

• In the age of partnership or ‘big pharma’ investment in small company development, large pharmaceutical companies often prioritize their resources to invest in non-rare disease development due to their higher likelihood of success and greater return on investment.
• Raising pre-approval awareness for rare diseases and orphan products is difficult because few journals and conferences focus specifically on these areas.
• Approved products for orphan indications are often more expensive than products for non-orphan indications, particularly when they offer a cure.
• Reimbursement remains a major hurdle, as insurers and government agencies may refuse to cover all or even some of the cost of the treatment, leading to lower market uptake and poor patient access.

Strategic Planning Enhances Orphan Drug Development Success

Anticipating the challenges of orphan product development with careful planning, a flexible strategy, and a creative mindset can effectively manage regulatory obstacles and improve outcomes. Working with a regulatory and development organization that has specialized experience in not just orphan drug designation requests but also orphan drug development, publication and presentation strategies, market access, and pricing and reimbursement improves your probability of success.

Advancing Orphan Drug Development with Facet Life Sciences

The road to developing orphan drugs is demanding, but it can be navigated successfully with the right knowledge and partner. Facet Life Sciences brings a breadth of regulatory and asset value development expertise, focusing not only on orphan drug designation but on the full orphan drug development lifecycle. We help sponsors address scientific and regulatory uncertainties, optimize clinical trial designs, and build strategies for market access and reimbursement. We will work with you to help both FDA and investors see the value and potential of your product.

Talk to expert at Facet Life Sciences today to overcome the complexities inherent to orphan drug development and bring innovative treatments to the rare disease community.