Tuesday, January 28, 2020

Treating Achondroplasia: eight years online

Happy New Year!


The Treating Achondroplasia blog is reaching eight years online and it has now received more than 380K visits from more than 160 countries. This has been quite a journey. New visitors may not know but it all started after I spent sometime talking with investigators, researchers and representatives from advocacy groups back in 2009 and 2010, trying to understand their points-of-view over achondroplasia. I realized that there were gaps on knowledge and a kind of disconnect between the scientific community and parents and families. Although there was research being pursued at that time, the interested community had very little access to it, either because it was not easy to filter the relevant information, or because that relevant information was delivered in hard jargon, not accessible to all. So, the blog started with the idea of translating the deep science language from those studies to a text that could help the lay reader to understand what was achondroplasia and what was being done to try to correct the growth impairment caused by the mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.

Since that time, many therapeutic strategies have been explored, as you can see browsing the blog's index page. Some of them have been successfully moved to clinical development, and the more advanced one, vosoritide, a C-type natriuretic peptide (CNP) analogue, is closer to reach the market, according with its developer, Biomarin.

Remember that you can always browse other articles of the blog to get more detailed info about achondroplasia and the mechanisms of action of the drugs we briefly mention here.

So, let's see with more detail what happened in 2019 with the research for therapies for achondroplasia. Below you will see a brief summary of the four molecules under test right now.

Vosoritide - Biomarin

The developer recently announced their plans to submit the results of the phase 3 study with vosoritide to the FDA during 2020, expecting to receive approval in 2021 for children over 6 years old. They also released more data on the long term extension study with participants from the phase 2 study. From the phase 3 study we learned that compared to placebo, vosoritide improved growth velocity by 1.9 cm in one year on average. The results from the phase 2 study revealed that the effect on growth seems to be sustained throughout the years. Furthermore, they also announced that the first two cohorts of the phase 2 study with infants and toddlers, of children 5 year-old or less, are fully recruited, and that the third cohort in infants is in progress at the moment I am writing this text.

To learn more about Biomarin's vosoritide status and plans, click on the following link that will lead you to their presentation at the JP Morgan event earlier given earlier this month.

TransCon CNP - Ascendis Pharma

Following the steps of Biomarin, Ascendis started the recruitment of volunteers for their natural history study, which is a requirement to enroll in the drug intervention study with their own CNP analogue. It seems that they have been able to start the recruitment of their phase 2 study with TransCon-CNP as well. Last year, they have also published the results of their pre-clinical studies and released information about the phase 1 study in healthy volunteers.The main difference between this asset and vosoritide is that it has been designed to be given once a week compared with the Biomarin's product, which is given in a daily injection. Those interested in joining Ascendis' trials could visit these links for more information:

Recifercept (TA-46) - Pfizer

Therachon, the original developer of TA-46, passed the ball to Pfizer, after the release of their phase 1 trial results. The molecule was then named recifercept. This drug is called a "ligand trap" and it was designed to capture the agents that normally activate FGFR3 before they are able to activate the mutated receptor. If FGFR3 remains inactive then growth can be restored. Pfizer has also started the natural history study that will allow volunteers to join the phase 2 study later. The following link will take you to more information about their natural history study:

Infigratinib (BGJ-398) - QED

The developer of infigratinib, a molecule designed to block FGFRs' intracellular pathways, has also started their natural history study. I am not aware if they have started their phase 2 study yet. This drug would work by "cutting" the wires that drive the chemical reactions elicited by FGFR3, leaving the chondrocytes able to resume their growth process. To learn more about their natural history study:




More news

Other experimental therapies have been reported lately, including a third CNP analogue by a Japanese developer, but they are still far away from clinical development now. Other positive perspectives come from studies using CNP and other drugs to modulate FGFR3 activities in skeletal dysplasias where FGFR3 is not mutated but still plays a relevant role in the bone growth impairment seen in those disorders. These are reassuring news since making available therapies for disorders such as dyastrophic dysplasias and RASopathies may help improving the quality of life of children affected by mutations in the respective causative genes.

Things are only getting better and we hope we will watch more news during 2020 bringing new hope and solutions for achondroplasia and many other skeletal dysplasias.





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