The development of therapies for rare diseases has been significantly aided by fast-tracked regulatory approval processes. These accelerated pathways, established by global authorities, aim to bring much-needed treatments to market more quickly. While these processes offer numerous benefits, they also introduce specific CMC risks that must be carefully managed.
At Quotient Sciences, we specialize in addressing unmet needs in rare disease treatment. Over the past five years, we have supported more than 50 development programs for rare diseases. In our latest webinar, we outline the challenges CMC face when developing these often life-saving treatments and discuss strategies to mitigate these risks. Below we highlight some of the key takeaways.
An unmet need
According to the National Institutes of Health (NIH), approximately 7,000 rare diseases affect between 25 and 30 million Americans. In the European Union, up to 36 million people live with a rare disease, while 300 million people worldwide are affected. Of the 7,000 known rare diseases, about 95 percent have no treatment. Many of these conditions are under-researched, resulting in few or no effective treatments available.
The smaller patient populations and associated market size for rare diseases mean that the potential financial return on investment is lower compared to treatments for more common conditions. This economic reality often makes pharmaceutical companies hesitant to invest heavily in developing new treatments for rare diseases. Recognizing this, global authorities have introduced additional regulations to encourage R&D investment in this area of high unmet clinical need.
Incentives for rare disease development
Key regulatory incentives have been established to promote the development of orphan drugs. For example, the Orphan Drug Act of 1983 in the US, and the Orphan Regulation of 1999 in the EU.
In the US, one of the primary incentives is market exclusivity, which grants companies exclusive marketing rights for their orphan drug for a period of 7 to 10 years. Additionally, expedited review timelines, tax credits for clinical research expenses, and waived prescription drug user fees help reduce costs and protect investments, making it more feasible for pharmaceutical companies to develop treatments for rare diseases. Accelerated pathways are also available to speed up the availability of these medicines to patients.
Traditional Timeline vs. Accelerated Pathway
For patients suffering from serious diseases and unmet clinical needs, the typical drug development timelines of up to 15 years can seem excruciatingly long. As a result, global health authorities have developed multiple pathways to expedite drug development and review times. The expedited approval is granted based on an agency finding that the drug is safe and effective for its intended use – exactly the same approval standard as that used for the traditional drug development pathway.
Accelerated approval simply allows the FDA to evaluate drugs based on surrogate endpoints or intermediate clinical outcomes that predict clinical benefit. Because these endpoints are expected to predict clinical benefit the agency can make the risk benefit calculation that an accelerated approval pathway’s benefits outweigh its risks – which are then rigorously confirmed in post-marketing confirmatory studies conducted after accelerated approval.
Examples of US pathways
In the US, several pathways are available to expedite the development and approval of these treatments. For instance, the Accelerated Approval pathway targets new medications that address unmet clinical needs. The Breakthrough Therapy designation is granted to drugs that demonstrate significant improvement over existing therapies. Additionally, Priority Review can be sought to reduce the review timeline to six months for therapies where no adequate treatments currently exist.
These expedited pathways can significantly reduce development timelines from the typical 10-15 years to as few as 3-5 years. However, the accelerated pace ultimately introduces several challenges and pressures on CMC teams.
What risks and challenges do CMC face?
- Smaller patient populations result in reduced commercial potential and limited research and development budgets.
- Developing stable and effective formulations for rare diseases is often difficult due to their unique and specialized nature.
- Recruiting participants for clinical trials is challenging due to the small and dispersed rare disease patient populations.
- Traditional manufacturing and supply chain models do not align with the small-scale, specialized needs of rare disease therapies.
How can CMC best manage these risks?
The accelerated submission pathways for orphan drugs offer a vital opportunity to bring much-needed therapies to patients with rare diseases more quickly. However, the associated risks require careful management through robust CMC strategies. In our latest webinar, Dr. Asma Patel, Vice President of Integrated Development Services, dives into more detail on some robust CMC strategies you can apply to manage these risks.
Learn how to identify creative development strategies for accelerated submission pathways, from early clinical studies through to commercial launch. Watch our webinar recording [link].