DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for achondroplasia — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAchondroplasia maps to a 8-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for achondroplasia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
fibroblast growth factor receptor 4 (FGFR4) — FGFR4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KH8 · 1.49 Å · ligand 1-[4-[(1~{R})-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-5-cyano-pyridin-2-yl]-3-[6-methanoyl-5-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3-(2-morpholin-4-ylethoxy)pyridin-2-yl]urea (VVW). Experimental structure, not a prediction.
What the evidence adds up to
In a phase 2 dose-finding study, 35 children aged 5 to 14 years with achondroplasia received daily subcutaneous vosoritide at doses from 2.5 to 30.0 μg per kilogram. Adverse events occurred in all 35 patients, serious adverse events in 4 (11%), and 6 discontinued therapy, one due to an adverse event. A dose-dependent increase in annualised growth velocity was seen up to 15.0 μg per kilogram in the first six months, and a sustained increase at 15.0 and 30.0 μg per kilogram for up to 42 months. The authors described the side-effect profile as generally mild.
A later extension trial followed 119 participants who had received 15 μg/kg/day of vosoritide for a mean of four years. At year three, the largest mean changes in health-related quality of life scores were in the physical domain (caregiver-reported 5.99, self-reported 6.32) and social domain (caregiver-reported 2.85, self-reported 6.76). Greater changes were seen in children whose height z-score increased by at least one standard deviation. The authors noted that untreated persons showed smaller age-related changes in these scores.
A real-world retrospective study from a single Portuguese centre reported on 27 children aged 2 to 14 years treated for at least six months. After 24 months in 15 children, mean height standard deviation score increased by +0.95 SD relative to an untreated achondroplasia-specific reference population and by +0.56 SD relative to children of average stature. Mean annualised growth velocity increased by +1.62 cm per year from baseline. Injection site reactions were the most common adverse drug reaction (n=14); no serious adverse drug reactions and no discontinuations due to adverse reactions were reported.
Regulatory approvals for vosoritide (Voxzogo) were granted by the US FDA and the European Medicines Agency. The US approval was accelerated under the rare paediatric disease criteria. The drug is associated with decreased blood pressure as a severe adverse event, which regulators judged to be outweighed by the benefit of addressing an unmet medical need. What remains missing are long-term data on functional outcomes beyond height, direct comparisons with other emerging therapies, and evidence on whether early treatment alters the serious complications of achondroplasia such as cranio-cervical junction compression or obstructive sleep apnea.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2019 · 221 citations · open access
C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia
AbstractBACKGROUND: Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification. METHODS: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia. A total of 35 children were enrolled in four sequential cohorts to receive vosoritide at a once-daily subcutaneous dose of 2.5 μg per kilogram of body weight (8 patients in cohort 1), 7.5 μg per kilogram (8 patients in cohort 2), 15.0 μg per kilogram (10 patients in cohort 3), or 30.0 μg per kilogram (9 patients in cohort 4). After 6 months, the dose in cohort 1 was increased to 7.5 μg per kilogram and then to 15.0 μg per kilogram, and in cohort 2, the dose was increased to 15.0 μg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses. At the time of data cutoff, the 24-month dose-finding study had been completed, and 30 patients had been enrolled in an ongoing long-term extension study; the median duration of follow-up across both studies was 42 months. RESULTS: During the treatment periods in the dose-finding and extension studies, adverse events occurred in 35 of 35 patients (100%), and serious adverse events occurred in 4 of 35 patients (11%). Therapy was discontinued in 6 patients (in 1 because of an adverse event). During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed with vosoritide up to a dose of 15.0 μg per kilogram, and a sustained increase in the annualized growth velocity was observed at doses of 15.0 and 30.0 μg per kilogram for up to 42 months. CONCLUSIONS: In children with achondroplasia, once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that appeared generally mild. Treatment resulted in a sustained increase in the annualized growth velocity for up to 42 months. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov numbers, NCT01603095, NCT02055157, and NCT02724228.).
Genetics in Medicine · 2024 · 21 citations · open access
Persistent growth-promoting effects of vosoritide in children with achondroplasia are accompanied by improvements in physical and social aspects of health-related quality of life
AbstractPURPOSE: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia. METHODS: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766). RESULTS: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with ≥1 SD increase in height z-score (physical: 11.36 [19.51], caregiver-reported [n = 38]; 8.48 [21.83], self-reported [n = 28]) (social: 5.84 [15.45] and 9.79 [22.80], respectively). To determine how domain scores may change with age in untreated persons, models were produced using observational/untreated-person data. A 1-year increase in age was associated with a change of 0.16 (SE, 0.55) and 0.16 (0.50), for caregiver-reported physical and social domain scores, respectively. Self-reported scores changed by 1.45 (0.71) and 1.92 (0.77), respectively. CONCLUSION: These data suggest that after 3 years of treatment, vosoritide demonstrates a positive effect on physical and social functioning among children with achondroplasia, particularly in children with a more pronounced change in height z-score.
Intractable & Rare Diseases Research · 2023 · 13 citations · open access
Vosoritide, a miracle drug, covering unmet need in achondroplasia: A regulatory update
AbstractDwarfism is a rare condition characterized by small stature. Achondroplasia is predominantly considered the leading cause of dwarfism. Although the condition is not life-threatening, it dramatically impacts the social life of the patient. The United States Food and Drug Administration (US FDA) first approved the drug Voxzogo (vosoritide) for achondroplasia. The drug also received approval from the European Medicines Agency (EMA) via the centralized procedure. The drug is associated with a decrease in blood pressure, a severe adverse event. However, this adverse event/risk has been overcome by benefits, i.e. fulfilling of unmet medical need. In the United States, the drug received accelerated approval as it satisfied the criteria of rare pediatric disease. This review includes a detailed orphan drug approval process with particular reference to vosoritide, which is considered a milestone for the treatment of achondroplasia.
Advances in Therapy · 2025 · 7 citations · open access
Real-World Safety and Effectiveness of Vosoritide in Achondroplasia: Results from a Single Center in Portugal
AbstractINTRODUCTION: Achondroplasia, the most common skeletal dysplasia, is caused by autosomal dominant gain-of-function pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene. Vosoritide, a C-type natriuretic peptide analog, is a first-in-class targeted treatment for achondroplasia that counteracts overactive FGFR3 signaling to stimulate endochondral bone growth. This retrospective cohort study evaluated growth, safety, and treatment compliance in children with achondroplasia receiving vosoritide under an early access program in Portugal. METHODS: Twenty-seven children aged 2-14 years with a genetically confirmed diagnosis of achondroplasia were treated with vosoritide at a single Portuguese center for at least 6 months between January 2022 and June 2024. The analysis included children with severe achondroplasia-associated complications. Anthropometric measurements collected to characterize the effect of vosoritide on growth included height standard deviation score (SDS) and annualized growth velocity (AGV). Student's t test was used for statistical comparisons. Safety and tolerability endpoints included adverse drug reactions and treatment adherence. RESULTS: In total, 15 children completed at least 24 months of treatment. After 24 months of treatment, mean variation in height SDS increased from baseline by + 0.95 SD (P ≤ 0.0001), referenced to an untreated achondroplasia-specific population, and + 0.56 SD (P ≤ 0.0001) relative to children of average stature. Additionally, mean AGV from baseline was 5.87 cm/year (95% confidence interval 5.14-6.60), resulting in a significant increase of + 1.62 cm/year (P ≤ 0.0001). Injection site reactions were the most common adverse drug reaction observed (n = 14); no serious adverse drug reactions were reported. There were no discontinuations due to adverse drug reactions. CONCLUSION: Vosoritide showed long-term effectiveness in a real-world Portuguese population of patients with achondroplasia. Vosoritide was also well tolerated, and patients showed good adherence to treatment. These findings were consistent with the outcomes of clinical trials and existing real-world experience.
Expert Opinion on Emerging Drugs · 2021 · 7 citations
Emerging therapies for Achondroplasia: changing the rules of the game
AbstractINTRODUCTION: Achondroplasia is the most common genetic cause of disproportionate short stature, affecting over 360,000 individuals. Serious complications contributing to significant morbidity in affected individuals include cranio-cervical junction compression and obstructive sleep apnea. Current clinically available treatments are predominantly symptomatic and associated with variable outcomes. We summarize the new precision investigational products that are currently in Phase 2 and Phase 3 clinical trials for the treatment of individuals with achondroplasia. AREAS COVERED: function in individuals with achondroplasia results in inhibition of normal endochondral ossification. A greater understanding of these molecular pathways through animal models has led to the development of several targeted therapies being tested in children, which we discuss in this review. EXPERT OPINION: The last decade has been game-changing in terms of new precision therapies for children with achondroplasia that have the potential to fundamentally change the natural history of this condition. The next decade will see how these therapies compare, if they might be used in combination, and evaluate the balance of their long-term benefits and harms.
World Journal of Current Medical and Pharmaceutical Research · 2024 · 0 citations · open access
Role of vosoritide drug on children's with achondroplasia
AbstractAchondroplasia is a genetic condition with an autosomal dominant inheritance pattern. It is caused by detrimental heterozygous FGFR3 gene mutations. Gain-of-function mutations in the FGFR3 gene impair chondrocyte differentiation and proliferation, which has a negative impact on the formation of new bone. Vosoritide, also known as voxzogo, is the first pharmacological intervention to receive approval for the treatment of achondroplasia. This therapeutic agent has been sanctioned for administration via at-home injections, which are to be performed under the supervision of a proficient nurse.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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