The Healthonauts: „Wir sehen bei Rare Diseases Bedarf an sehr individueller strategischer Beratung“
When it comes to drug development in rare diseases, there are certain hurdles that must be taken compared to more prevalent diseases:
1. Target Discovery:
Understanding the intricate biology underlying a disease is crucial for identifying effective treatment targets. However, in rare diseases both the etiology of the disease as well as the link to manifesting symptoms are often incompletely understood, making it difficult to find targeted treatments. Novel technologies like next-generation sequencing offer promise in unraveling the genetic basis of many rare diseases, paving the way for targeted interventions, including new modalities with long-lasting effects such as gene therapies and RNA-based therapeutics.
2. Preclinical Research:
Preclinical Drug Development typically involves extensive laboratory and animal studies to assess safety, efficacy and pharmacological properties. Yet, accurately modeling rare diseases in laboratory settings necessitates a comprehensive understanding of their pathophysiology, which can be challenging given the limited disease knowledge and the lack of predictiveness of models for novel modalities, when it comes to long-term efficacy and safety.
3. Clinical Research:
Clinical Development involves testing safety in healthy volunteers (or sometimes in patients) in Phase I, efficacy in a smaller number of patients in Phase II and confirming findings compared to placebo or SoC in a large and preferably diverse group in Phase III. Given small number of patients with a rare disease, often with low diagnostic accuracy, it can be challenging to recruit an adequate cohort for clinical trials across these phases. Moreover, in case of severe phenotypes, common to rare diseases, the use of a placebo group can be unethical. Innovative trial designs, decentralization and implementation of real-world evidence (RWE) can help overcome those challenges.
4. Market Entry:
With a small patient pool, orphan drugs may in themselves not be commercially attractive for developers, often leading to higher prices to ensure economic viability. Specific orphan instruments offer additional incentives, such as prolonged market exclusivity or developers venturing into the orphan space. For newer, high-priced modalities such as gene therapies, payers and pharma players are exploring new reimbursement models. Moreover, patients and families sometimes take active roles in advocating for the reimbursement of expensive but life-saving drugs.
5. Post marketing commitments:
The journey of drug development extends into the realm of post-marketing surveillance and collection of a body of RWE. Especially for novel technologies such as gene and cell therapies, RWE emerges as a crucial tool in evaluating long-term safety and efficacy, complementing traditional clinical trial data. Active collaboration with patients and advocacy groups is important for successful post-marketing strategies.
