The evolution of rare disease therapies

Although individually uncommon, rare health conditions collectively affect more than 300 million people worldwide. To mark Rare Disease Day on 28 February, Shauna Aherne, President, Medical Excellence, Specialized Services takes a look at some of the current trends and developments in the rare disease space, and explore the pivotal role medical affairs plays in helping bring vital drugs to those facing a challenging future.

It was the Orphan Drug Act of 1983 in the US, followed by similar regulations in Europe and other regions, that heralded a turning point for rare diseases. These acts provided incentives such as tax credits, market exclusivity, and regulatory support, encouraging pharmaceutical companies to invest in new therapies. Until then, rare conditions were often overlooked due to their small patient populations and limited commercial incentives.

Today the landscape has evolved further, with advancements in genomics enabling scientists to pinpoint the specific genetic mutations underlying many rare diseases. This shift toward precision medicine has opened up exciting new avenues for developing highly targeted therapies, attracting significant funding, and giving hope to millions of patients.

At the same time, the rise in online communications has enabled once isolated individuals and their families to find each other and a voice. Well-organized patient-advocacy groups now play a crucial role in raising awareness, funding research, and influencing policy, further accelerating drug development.

More recently we’ve seen a number of key trends emerge in this area:

Gene and cell therapies: With the rise of CRISPR and other gene-editing technologies, there’s a growing focus on developing curative therapies for genetic rare diseases. These aim to correct the underlying genetic defects rather than just alleviating symptoms.

For conditions such as Leber congenital amaurosis (a rare inherited blindness), gene therapies have progressed from the experimental stages to FDA-approved treatments.

Existing asset expansion: Given the challenges of developing new treatments from scratch, leveraging existing assets as the backbone for new indications has become a popular strategy. Existing drugs, already approved for other conditions, can be tested for treating rare diseases, speeding up the time to market.

RNA-based therapies: Antisense oligonucleotides bind to RNA and can be used to treat genetic drivers of disease and alter the course of heritable diseases. RNA interference (RNAi), in which genes can be suppressed, is particularly promising for metabolic disorders and neurological conditions, such as spinal muscular atrophy and Duchenne muscular dystrophy.

Enzyme replacement therapies: ERTs along with substrate-reduction therapies are being increasingly developed for disorders such as Gaucher disease and Fabry disease.

Monoclonal antibodies: These have shown great promise in treating rare autoimmune conditions such as hereditary angioedema, which causes severe swelling, leading to targeted and effective treatments.

Digital health tools: With rapid advancements in technology, there’s an increased use of digital tools, including AI-driven diagnostics and patient-monitoring apps, being. These tools, integrated into clinical trials for example, are enhancing patient recruitment and real-time data collection.

As drug development has evolved, so too have commercialization strategies. Companies are now adopting more patient-centric approaches, often working closely with advocacy groups from the early stages of development. This engagement helps build awareness, facilitate recruitment for clinical trials, and generate support for expedited access to therapies. Real-world evidence generation has also become essential to demonstrate long-term value and secure favorable reimbursement.

Rare disease therapies often command premium pricing due to the high unmet medical need and lack of alternative treatments. Moreover, smaller and more specialized sales forces can effectively target key centers of excellence, reducing overall commercialization costs.

Yet challenges remain. The dispersed nature of rare disease patients can complicate diagnosis and access, requiring more targeted and often digital engagement strategies. Additionally, payers are increasingly scrutinizing the high costs of these therapies, necessitating robust evidence of long-term value.

Key factors to consider when evaluating the commercial viability of a rare disease therapy include:

• Prevalence and diagnosis rates: Understanding the true size of the patient population and diagnostic capabilities is crucial.
• Clinical differentiation: The therapy must offer significant clinical benefits over existing treatments or fill a gap in the current standard of care.
• Reimbursement landscape: Securing favorable pricing and reimbursement depends on demonstrating value to payers and meeting stringent evidence requirements.

How medical affairs can help

Medical affairs plays a pivotal role in both drug development and commercialization. That’s because, given the specialized nature of rare diseases, there’s often limited clinical knowledge and awareness among healthcare providers (HCPs).

Medical affairs teams act as a bridge, offering vital education, facilitating key opinion leader (KOL) engagement, and supporting patient-advocacy initiatives. In the post-approval phase, medical affairs continues to be instrumental by generating real-world evidence, educating HCPs on appropriate use, and addressing queries related to the therapy’s long-term efficacy and safety. The function also supports interactions with payers and regulatory bodies, providing the necessary data to secure and maintain market access.

Medical affairs can help with:

Clinical trial support: Engaging with investigators and KOLs to make sure trial designs meet the needs of the patient population and facilitate effective recruitment.

KOL and HCP engagement: Establishing early and ongoing relationships with KOLs and educating HCPs about diseases, clinical trial opportunities, and therapeutic options.

Patient advocacy and support: Collaborating with advocacy groups to understand patient needs, assist in education, and support awareness campaigns.

Evidence generation: Collecting and analyzing real-world data to demonstrate a therapy’s value and support reimbursement efforts.

Post-approval education: Providing continuous medical education to HCPs to ensure a therapy’s proper use and to monitor for adverse events.

The reimbursement environment in particular presents a number of challenges for companies due to the high costs of drug development and the limited long-term data available at launch. Payers often demand robust evidence of clinical efficacy, durability, and real-world outcomes before granting access, but these can be difficult to show in the rare disease space.

To overcome these challenges, companies are adopting innovative strategies such as outcomes-based agreements, which link payments to a therapy’s performance in a real-world setting. They’re also promising to invest in long-term observational studies to collect data on the therapy’s impact, as well as running patient-support programs to provide diagnostics, financial aid, and education to enhance access and adherence. Again, these are all areas that medical affairs can help with.

As the rare disease therapy space evolves at a rapid pace due to scientific and technological advances, pharma and biotech companies face challenges on numerous fronts – from early-stage development through to creating an effective commercialization strategy and beyond. Engaging with an experienced medical affairs partner can help you navigate these obstacles, ensuring more people with rare diseases can get the therapies and support they need.