Major findings

Vosoritide is the first approved pharmacological treatment for achondroplasia and is indicated for at-home injectable administration by a trained caregiver. 3 explored parents' and children's experiences of initiating vosoritide and administering this treatment at home.

New therapeutic approaches have been established in the field of rare skeletal diseases (e.g. for osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia, and fibrodysplasia ossificans progressiva). 4 explained that after elucidation of the underlying genotypes and pathophysiologic alterations of these diseases, new treatment options have been designed. Most drugs are based on an interaction with the disease-specific cascade of enzymes and proteins involved in the disease. Thereby an approved treatment is available for children with severe forms of hypophosphatasia and hypophosphatemic rickets (asfotase alfa, burosumab). Additionally, there are different phase 3 trials ongoing assessing the efficacy and safety of drugs for osteogenesis imperfecta, achondroplasia, and fibrodysplasia ossificans progressiva (denosumab, vosoritide, palovarotene). Because all these diseases are rare, the number of investigated patients in the trials is small, and the knowledge about rare side effects and long-term outcome is limited. Therefore it is recommended to treat the patients in specialized centers where the effects of the drugs can be evaluated and data about safety, side effects, and efficacy can be collected. Based on the fact that most drugs for rare diseases are highly expensive clear indications for start of a treatment, evaluation of the therapy and recommendations how long a treatment has to be administrated are urgently needed.

Reasons for Side Effects

The reasons for side effects of vosoritide are not fully understood, as these drugs are still relatively new and there is limited information available on their long-term safety and efficacy. However, it is possible that the side effects are related to the unexpected consequences of these drugs acting on specific cellular pathways, which influence bone formation.

Common Side Effects

Visual Field Constriction

Vigabatrin has been associated with asymptomatic visual field constriction in longer-term observational studies. 2 and 1 found no major side effects were detected in initial randomized controlled trials, but longer-term observational studies have subsequently identified its use is associated with asymptomatic visual field constriction.

Side Effects Management

Visual Field Constriction

Regular eye examinations should be performed during vigabatrin administration to detect and manage visual impairment early.

Comparison Between Studies

Commonalities Between Studies

All three studies focus on new drug therapies for rare diseases, highlighting the challenges in treating these diseases and the need for further research on these treatments.

Differences Between Studies

The three studies focus on different rare diseases. The two studies on vigabatrin focus on treatment for epilepsy, while the study on vosoritide focuses on treatment for achondroplasia. The studies on vigabatrin also used observational studies to investigate the drug's long-term side effects, while the study on vosoritide used qualitative research to explore parents' experiences with administering the drug.

Considerations for Real-World Applications

While these research findings demonstrate the promise of new drug therapies like vosoritide in treating rare diseases, these drugs are still in their early stages of development, and there is still limited information available on their long-term safety and efficacy. Therefore, it is important to consult with a physician and understand the potential side effects and risks when considering using vosoritide.

Limitations of Current Research

These studies have a limited sample size due to the rarity of the diseases, which makes them difficult to generalize. The study on vosoritide used qualitative research to explore parents' experiences with administering the drug, which does not provide information on the drug's long-term effects.

Future Research Directions

Larger, long-term clinical trials are needed to evaluate the safety and efficacy of these drugs. The ethical and social aspects of using these drugs in the treatment of rare diseases should also be considered.

Conclusion

Vosoritide is the first approved pharmacological treatment for achondroplasia, but knowledge about rare side effects and long-term outcome is limited. It is important to consult with a physician and understand the potential side effects and risks when considering using vosoritide. Future research should provide additional data on the safety and efficacy of these drugs.