What are your thoughts on this article?
Judging by the article recently published by the Reuters agency, we have dawned to the beginning of a new era: An era in which rare pediatric diseases aren´t forgotten, but faced and in a near future fought, thanks to the FDA´s new approach in such important matters.
The FDA is about to eliminate a major milestone in research of such rare illnesses, by simplifying the procedure of developing drugs, eliminating the obligation of certain trials and reducing patient enrollment and the number of those on placebo, by letting companies work together and test different drugs in the same clinical trial. This could pose as quite a challenge for the correct drug development due to the small number of patients worldwide with any given rare disorder, but thanks to this guidance, its final goal is to increase the efficiency of drug development.
The draft guidance was put together thanks to the collaboration of the FDA and the European Medicines Agency, using Gaucher´s disease as an example, and underlining that this proposal can be extrapolated to other rare pediatric disorders. For the next two months, the guidance is open to comment, after which the FDA will release a final draft and will make it a reality.
Gaucher´s disease is one of the most common lysosomal storage disorders, and it´s considered an orphan disease because it affects less than 200,000 people. It has been classified in three phenotypes on the premise of the presence or absence of neurological symptoms, being type I the most prevalent, type II the most lethal and type III a more chronic manifestation. This guidance recommendations regarding drug development apply to Gaucher disease with non-neurological manifestations in naïve pediatric patients under treatment with type I and type III phenotypes. It is important to underline that the age and onset of symptoms tend to correspond with severity and future manifestations.
One should take under consideration when planning future studies disease-modifying factors, such as age, mutation or residual enzyme activity. Exploratory biomarkers such as markers of lung and bone disease or the measurement of bone density should also be kept in mind. Enrolling patients who are as homogeneous as possible will increase the chances of finding a treatment effect. This need should not detain the access to a drug for age subgroups that are harder to study because of their heterogeneity. In this last case, we can extrapolate, eluding unnecessary studies, maximizing efficiency, reducing the burden of testing to patients and assigning resources to address more relevant matters.
Nevertheless, other approaches are welcome, with a prior justification by the sponsor of the choice of each strategy. Additionally, sponsors should consult the appropriate regulatory agencies before the initiation of any clinical trials.
The current standard in pediatric patients suffering Gaucher´s disease consist of enzyme replacement therapy (ERT), which is used to treat non- neurological manifestations in type I and type III phenotypes. Placebo-controlled trials of new ERTs in pediatric patients are considered unethical due to the demonstrated clinical improvements show by the current ERTs. However, new non-ERT drug products may be studied using placebo add-on design while still using ERT.
The studies conducted until now have not correctly addressed all the major medical needs across all pediatric age groups, like for example the low number of patients under 2 years’ old that have been enrolled in clinical trials. Also, the disease´s impact on growth rate, bone and other manifestations have not been studied in depth with the available ERT therapy or the development of drugs with more practical routes of administration could benefit all pediatric ages and may improve the existing ERTs.
In such prospective studies is vital the long term follow-up to evaluate the long-term efficacy and safety of treatment on symptoms in pediatric patients. All children born to treated mothers should also be evaluated long term. To do so, the FDA recommends across-registry agreement on a uniform set of core data elements to be collected by all present and future Gaucher disease registries.
Finally, even though it is not reflected on this guidance, there is a vital need for finding treatment for pediatric patients with neurological manifestations (types II and III), because current ERT therapy has no effect on them. With all the multi discipline coverage portrayed in this guidance, it is a matter of time that patients suffering rare conditions start seeing a gradual boost in research in the present, which will mean a possible improvement in treatment and understanding in a nearer future.