Researchers Highlight Need for Disease Registries Independent of Pharmaceutical Industry

As rare disease registries to assess orphan drugs are mainly established by the pharmaceutical industry, researchers argued post-marketing registries, functioning as marketing tools, have an underestimated influence on clinical practice.

In a position statement appearing in Orphanet Journal of Rare Diseases, the researchers reported a “virtual absence” of independent registries for rare diseases. This finding led them to urge healthcare professionals, patient organizations, and government and/or regulatory authorities to take responsibility for generating independent data that can be leveraged for evaluating registration and reimbursement decisions, and optimal patient management for rare diseases.

The market for orphan drugs continues to expand at an annual growth rate of 11.2% and by 2024, drugs for rare diseases are expected to account for nearly 1 in 5 (18%) of global prescription drug costs. Literature suggests the pharmaceutical industry is interested in orphan drugs as they are associated with a higher return on investment compared with drugs for more common diseases.

Authors outlined the case of enzyme replacement therapy (ERT), which first showed promise in Gaucher disease based on treatment with Ceredase, a placental derived enzyme. After evidence showed that not all patients needed the treatment and those who did could often be treated with a lower dose, a recommendation was issued for collection of better evidence on the expensive therapy’s appropriate use.

Genzyme corporation (now a Sanofi company), which markets the drug, created a global registry in 1991 complete with analyses, data on both treated and untreated patients, and publications being run, financed, and supported by the company.

“Interestingly, none of the Gaucher Registry publications reported on limitations of treatment with enzyme replacement therapy,” authors wrote. “A similar approach for Genzyme’s (no Sanofi) oral drug for Gaucher (Eliglustat) resulted in a treatment algorithm publication, without mentioning the possibility of the patient having mild disease status that does not require treatment.”

Following the approval of Shire’s (now Takeda) similar ERT in the European Union in 2014, another global post-marketing registry was established and the 2 pharmaceutical companies sponsored symposia, round tables for educational purposes, and investigator-initiated studies on the drug.All of these actions often led to recommendations for early initiation of the therapy or population screening.

The researchers outlined a similar case with Fabry disease, which was targeted for ERT use following the therapy’s success in Gaucher disease. Both Genzyme and Shire were able to market their therapies concurrently in the European Union, and 2 global registries were created based on an European Medicines Agency mandate. However, according to the authors, there have been no data exchange or collaborative analysis between the 2 companies. Since its approval for use in Fabry disease, ERT has proven less effective in this indication, and the authors argued a lack of knowledge in several aspects of the disease may hamper the ability to draw any robust conclusions.

“There remains real uncertainty about whom to treat, at what dose and for how long,” they explained. “It is clear that the registries were not set up to be able to answer these questions, since crucial data e.g. on patients’ disease phenotype, were usually missing and results from the different antibody assays used by the companies could not be compared.”

As a result, some independent initiatives have emerged, although long-term uncertainty about the effectiveness of the treatment has affected reimbursement decisions.

Reference: Hollak CEM, Sirrs S, van den Berg S, et al. Registries for orphan drugs: generating evidence or marketing tools? Orphanet J Rare Dis. Published online September 3, 2020. doi: 10.1186/s13023-020-01519-0