During the recent International Skeletal Disease Society - ISDS 2013 Meeting, which took place in Bologna in the end of August, Biomarin presented the results from two of the pre-clinical studies performed with the C-type natriuretic peptide (CNP) analogue BMN-111.
One of the studies, presented by Laurence Legeai-Mallet from the Hôpital Necker Enfants Malades, Paris, showed new results on tests performed in mice bearing a mutation in the FGFR3 (Y367C) gene that resembles the one which causes achondroplasia in humans (G380R). (1) They showed that daily subcutaneous administration of BMN-111 in young mice bearing the Y367C mutation led to the attenuation of the achondroplasia phenotype (clinical features).
The use of this CNP analogue resulted in the following changes, according to the authors:
- Significant increase in the length of the axial (column) and appendicular (members) skeleton;
- Attenuation of the skull flattening;
- Increase of size of paws and digits;
- Straightening of tibias and femurs;
Furthermore, when examining the growth plate structure, the authors found that there was a rescue of the height and the architecture of the different growth plate zones.
These new results add to others already published by the same group in the last two years. (2-4) Although one cannot be sure that results found in an animal model will be 100% reproduced in humans, the similarity of the conditions here (model and human) allows researchers to balance the expectations about any possible outcomes in clinical studies.
The BMN-111 study in monkeys
During the ISDS meeting, Biomarin also presented for the first time (to my knowledge) the results from one BMN-111 study performed in healthy young monkeys. (5) Outcomes from this study have been announced by Biomarin in previous press releases and public (financial or general) presentations but detailed results have never been released before.
In summary (of the summary published in the meeting website), the study showed that, after about 4 weeks of treatment, BMN-111 led to a dose-dependent increase in the:
- animals’ axial and appendicular length;
- levels of alkaline phosphatase (ALP; a marker of bone metabolism);
- volume and width of growth plates.
1. Legeai-Mallet L et al. Achondroplasia: from gene identification to therapeutic approaches. Presented at the International Skeletal Disease Society - 11th ISDS 2013 Meeting, August 28-30, 2013, Bologna, Italy.
2. Lorget F et al. BMN 111, a CNP analogue, rescues femur growth and growth plate
architecture in a severe model of Fgfr3-related chondrodysplasia. Abstract 17, presented at the International Skeletal Disease Society - 10th ISDS 2011 Meeting, Palm Cove, Australia. (link unavailable on Sep 7, 2013).
3. Lorget F et al. Pharmacological evaluation of a CNP analogue for the treatment of achondroplasia. Presented at the 2012 ASHG Annual Meeting San Francisco, US.
4. Lorget F et al. Evaluation of the therapeutic potential of a CNP analog in a FGFR3 mouse model recapitulating achondroplasia. Am J Human Gen 2012; 91: 1108-14. (free access)
5. O’Neill C et al. Bone growth and hemodynamic activity in normal monkeys of a C-type natriuretic peptide analog (BMN 111), a possible treatment for achondroplasia. Presented at the International Skeletal Disease Society - 11th ISDS 2013 Meeting, August 28-30, 2013, Bologna, Italy.