The Pros and Cons in each different treatment for Achondroplasia

This recent study1 by Dr. Wiktoria Wrobel (Medical University of Lublin, Poland) brings together the different pharmacological treatments for achondroplasia, both current and potential, highlighting the advantages and disadvantages of each, making it a great comprehensive review.
The many complications of achondroplasia, both orthopaedic and neurological, make its treatment necessary and urgent in order to minimise and prevent disability. Searching for a medicinal approach to reduce the impact of this condition has been the focus of many research centres around the world, and different approaches are being tried as we speak (see table 1). At the moment, the most advanced investigations involve growth hormone therapy (rhGH) and vosoritide (analog of C-type Natriuretic Peptide from Biomarin).
Table 1 - Classification of Drugs According to the Target of Action | |
Target of Action | Drug Name |
FGFR3 | sFGFR3 (recifercept) |
Inhibitors of HMG-CoA (statins) | |
Tyrosine kinase inhibitor (infigratinib) | |
FGFR 1–4 inhibitor (ASP5878) | |
FGFR3 antibody (vofatamab) | |
NPR-B | CNP analogue (vosoritide) |
Sustained-release CNP (TransCon CNP) | |
MAPK pathway | Meclizine |
Chondrocyte nucleus | rhGH |
PTH/PTHrP |
Benefits and drawbacks of different drug therapies in achondroplasia
This study includes the potential impacts (see tables 2 and 3) of drugs on achondroplasia symptoms other than short stature, including their effects on spinal canal stenosis, the narrowing of the foramen magnum and the proportionality of body structure. Addressing these effects could significantly improve people's quality of life, possibly reducing the frequency and necessity of hospitalisation and painful surgical procedures, which are currently the only therapeutic options used. The criteria for a good drug for achondroplasia are best met by recombinant human growth hormone at present and will potentially be met by vosoritide in the future, while the rest of the drugs are in the early stages of clinical trials.Table 2 - Benefits of different drug therapies in achondroplasia | ||
---|---|---|
Drug Name | Benefits for People | Benefits for Animals |
Clinically used drugs | ||
Recombinant human growth hormone (rhGH) |
|
|
Drugs in different phases of clinical trials | ||
C-type natriuretic peptide (CNP) analog: vosoritide |
|
|
C-type natriuretic peptide prolonged-released: TransCon CNP |
|
|
Infigratinib (NVP-BGJ398) |
|
|
Soluble recombinant human fibroblast growth factor receptor 3 (soluble FGFR3): recifercept |
|
|
Vofatamab (monoclonal antibody specific for FGFR3) |
|
|
Meclizine |
|
|
Statin |
|
|
ASP5878 |
|
|
Parathyroid hormone (PTH) |
|
|
Source: Wrobel W. Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review. Int J Mol Sci. 2021;22(11):5573. Published 2021 May 25. doi:10.3390/ijms22115573
Table 3 - Drawbacks of different drug therapies in achondroplasia | ||
---|---|---|
Drug Name | Drawbacks for People | Drawbacks for Animals |
Clinically used drugs | ||
Recombinant human growth hormone (rhGH) |
|
|
Drugs in different phases of clinical trials | ||
C-type natriuretic peptide (CNP) analogue: vosoritide |
|
|
C-type natriuretic peptide prolonged-released: TransCon CNP |
|
|
Infigratinib (NVP-BGJ398) |
|
|
Soluble recombinant human fibroblast growth factor receptor 3 (soluble FGFR3): recifercept |
|
|
Vofatamab (monoclonal antibody specific for FGFR3) |
|
|
Meclizine |
|
|
Statin |
|
|
ASP5878 |
|
|
Parathyroid hormone (PTH) |
|
|
Source: Wrobel W. Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review. Int J Mol Sci. 2021;22(11):5573. Published 2021 May 25. doi:10.3390/ijms22115573
Conclusions
This study demonstrates the commitment of various research centres in developing treatments for achondroplasia, however, even if these treatments are cleared for widespread use, they will not improve all the symptoms associated with achondroplasia. Although they provide the benefit of increasing bone length, their effects on important aspects, such as disproportionality, the axial skeleton (the part of the skeleton that consists of the bones of the head and trunk) and the foramen magnum, have unfortunately not been confirmed. Each of these aspects entails further complications that leave their mark on the daily lives of patients with achondroplasia.
The author also concludes that the ideal drug for achondroplasia should be small in size to readily penetrate the growth plate; specific for FGFR3 and effectively inhibit its signaling pathway. As a long term therapy, its production costs should be as low as possible, and the form of drug administration should be easy and acceptable for children. In addition, side effects should be minimised to the level of dose tolerance.
The criteria for a good drug for achondroplasia are best met by recombinant human growth hormone at present and will potentially be met by vosoritide in the future, while the rest of the drugs are in the early stages of clinical trials.
Visit this page for achondroplasia's drug Research and Development (R&D) table (in Portuguese).
Read the full article here.
Sources:
1. Wrobel W, Pach E, Ben-Skowronek I. Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review. Int J Mol Sci. 2021;22(11):5573. Published 2021 May 25. doi:10.3390/ijms22115573