Treating achondroplasia: news on drug development

News from the front!

Vosoritide

During their recent annual R&D Day, Biomarin released 42 month results from the long term study with vosoritide in kids that participated in the phase 2 study. The average growth velocity in kids using the 15mcg/kg dose was sustained and, during the period, the average additional growth compared to baseline was 5.7cm (Figure 1). Vosoritide keeps showing a good safety profile with no relevant adverse event reported so far (check the results here).

Figure 1. Vosoritide: sustained increase in growth velocity after 42 months with 15mcg/kg dose.

From Biomarin's R&D Day presentation, available here.

The phase 3 study with vosoritide is now fully enrolled and headline results are planned to be released in 4Q19. The phase 2 study with infants is now enrolling (Figure 2). This study is exploring safety and efficacy in a younger population and, if successful, will provide evidence to start the therapy earlier. It is predicted that with earlier intervention, benefits from therapy might be greater than what has been seen in older kids.

Figure 2. Phase 2 study with vosoritide in infants.

From Biomarin's R&D Day presentation, available here.

If the phase 3 study is successful, vosoritide may become available in 2020, after being approved by the FDA and other major regulatory agencies. Initially, following the current regulations, it would be approved only for kids over 6 years-old. Approval for younger kids will only be granted after the phase 2 study in infants results become available, provided they are positive, too.
 
TransCon CNP

On November 28th, Ascendis Pharma announced the results from the phase 1 study with their own version of CNP (C-type natriuretic peptide). Ascendis released a summary of the results of the phase 1 study in healthy adults showing that TransCon CNP was well tolerated and had the same safety profile compared to placebo with all doses tested. This means that there were neither adverse events that would be expected as a consequence of CNP's natural activity, nor unexpected ones. The study also confirmed the long TransCon CNP half-life seen in animal tests, which will allow a weekly dose to treat achondroplasia. 

TransCon CNP is in fact a transport system, in which the unmodified CNP is linked to a carrier molecule that allows this peptide to bypass the body enzyme neutralizing system that usually cleans peptides from the blood. You can visit the developer's website here, where you can find more information about their carrier system.

These results are good news for the community as TransCon CNP, if proven safe and efficient in the next steps of its development, may become a fair alternative to vosoritide, with the advantage of the weekly dosing. To build trust, It would be good if the developer published full results from their animal studies beyond the limited information released in past medical meeting presentations.

The regulatory challenge

One important question for drug developers is how to convince regulators that any drug developed for achondroplasia should be tested as earlier as possible in the group of affected children that will likely benefit the most from them. By continuing to follow the standard drug development path elaborated for common diseases, regulators may be in fact slowing down drug development and hindering the success of potential therapies for rare genetic disorders such as bone dysplasias. As achondroplasia starts before birth, setting hard endpoints for studies on older kids may hamper researchers to recognize all the potential benefits those potential therapies could bring if they were tested in a more appropriate population. And could lead to development failures. There are some significant examples of failures of promising therapies in the recent past, as we already mentioned in previous articles in this blog.