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Study · Non-randomized trial · n = 30 · 2026

8 results

A phase II basket trial of vosoritide in children with RASopathies, ACAN, and NPR2 deficiency.

Dauber A, Zhang A, Shafaei N, Seaforth R, Pitner K, Dham N, Kanakatti Shankar R, Merchant N

The Journal of clinical endocrinology and metabolism1 Aug 2026Cited by 2 (Europe PMC)

PMID41967490 (opens in a new tab)PMCIDPMC13466934 (opens in a new tab)DOI10.1210/clinem/dgag157 (opens in a new tab)PepBankPUB-41967490
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Summary

ContextGenetic defects in many biological pathways, including activation of the Ras-MAPK pathway, cause short stature. Vosoritide, a C-type natriuretic peptide analog that inhibits this pathway, has been approved for use in achondroplasia.ObjectiveTo determine whether vosoritide improves growth in children with disorders of the Ras-MAPK pathway, including RASopathies, ACAN, and NPR2 deficiency.DesignProspective Phase 2 basket trial.SettingAcademic medical center.ParticipantsThirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.InterventionSix-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.Main outcome measuresCo-primary outcomes included incidence of adverse events, change in annualized growth velocity (AGV), and height standard deviation scores.ResultsThe AGV increased from 4.53 ± 1.61 cm/year to 8.09 ± 1.58 cm/year with treatment (P < .0001). This corresponded to a 4.0 SD (95%CI 3.08-4.91) increase in age and sex-adjusted AGV Z-score (P < .0001). The increase in AGV was seen in all genetic subgroups. There was a height increase of 0.65 SD (95%CI 0.53-0.77) in the treatment vs observation period (P < .0001).Short-term safety was reassuring, with mild injection site reactions being the most common adverse events. However, with longer use, 5 subjects discontinued medication due to adverse events, including 3 slipped capital femoral epiphyses and 4 cases of genu valgum.ConclusionVosoritide led to marked increases in growth velocity in children with RASopathies, ACAN, and NPR2 deficiency, raising the possibility that vosoritide could be an effective precision medicine for all growth disorders affecting the MAPK pathway.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

  1. 01HumanNon-randomized trialEfficacy outcome

    In children with RASopathies, ACAN or NPR2 deficiency, vosoritide increased AGV from 4.53 ± 1.61 to 8.09 ± 1.58 cm/year (P < .0001).

    In plain wordsIn children with these growth disorders, vosoritide increased growth velocity compared with observation.

    Peptide
    Vosoritide
    Outcome
    IncreaseAnnualized growth velocity
    Study

    n = 30

    Comparator
    Observation period
    Analysis
    Primary
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    15 µg/kg/day · subcutaneous · 12 monthsAs given in this study (human).

    Measurements

    Annualized growth velocity
    4.53 cm/year
    observation period
    SD of annualized growth velocity
    1.61 cm/year
    observation period
    Annualized growth velocity
    8.09 cm/year
    vosoritide treatment
    SD of annualized growth velocity
    1.58 cm/year
    vosoritide treatment

    Source sentences

    Summary
    The AGV increased from 4.53 ± 1.61 cm/year to 8.09 ± 1.58 cm/year with treatment (P < .0001).
    4 context sentences
    Summary · context
    Co-primary outcomes included incidence of adverse events, change in annualized growth velocity (AGV), and height standard deviation scores.
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.
  2. 02HumanNon-randomized trialEfficacy outcome

    In children with these growth disorders, height increased by 0.65 SD during vosoritide treatment versus observation (95% CI 0.53-0.77, P < .0001).

    In plain wordsIn children with these growth disorders, height scores increased more during vosoritide treatment than observation.

    Peptide
    Vosoritide
    Outcome
    IncreaseHeight standard deviation score
    Study

    n = 30

    Comparator
    Observation period
    Analysis
    Primary
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    15 µg/kg/day · subcutaneous · 12 monthsAs given in this study (human).

    Measurements

    Height SD score increase, treatment vs observation
    0.65 SD
    vosoritide treatment vs observation
    95% CI lower limit of height SD score increase
    0.53 SD
    vosoritide treatment vs observation
    95% CI upper limit of height SD score increase
    0.77 SD
    vosoritide treatment vs observation

    Source sentences

    Summary
    There was a height increase of 0.65 SD (95%CI 0.53-0.77) in the treatment vs observation period (P < .0001).
    4 context sentences
    Summary · context
    Co-primary outcomes included incidence of adverse events, change in annualized growth velocity (AGV), and height standard deviation scores.
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.
  3. 03HumanNon-randomized trialSafety outcome

    In children with these growth disorders, short-term safety was reassuring, with mild injection site reactions as the most common adverse events during vosoritide treatment.

    In plain wordsIn children with these growth disorders, mild injection site reactions were the most common adverse events in the short term with vosoritide.

    Peptide
    Vosoritide
    Outcome
    Not applicableInjection site reactions
    Study

    n = 30

    Analysis
    Primary
    Outcome group
    Adverse events · Whole body
    Studied dose
    15 µg/kg/day · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    Short-term safety was reassuring, with mild injection site reactions being the most common adverse events.
    4 context sentences
    Summary · context
    Co-primary outcomes included incidence of adverse events, change in annualized growth velocity (AGV), and height standard deviation scores.
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.
  4. 04HumanNon-randomized trialEfficacy outcome

    In children with these growth disorders, vosoritide increased adjusted AGV Z-score by 4.0 SD (95% CI 3.08-4.91, P < .0001).

    In plain wordsIn children with these growth disorders, vosoritide increased adjusted growth velocity scores compared with observation.

    Peptide
    Vosoritide
    Outcome
    IncreaseAge- and sex-adjusted AGV Z-score
    Study

    n = 30

    Comparator
    Observation period
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    15 µg/kg/day · subcutaneous · 12 monthsAs given in this study (human).

    Measurements

    Increase in age- and sex-adjusted AGV Z-score
    4 SD
    treatment vs observation
    95% CI lower limit of AGV Z-score increase
    3.08 SD
    treatment vs observation
    95% CI upper limit of AGV Z-score increase
    4.91 SD
    treatment vs observation

    Source sentences

    Summary
    This corresponded to a 4.0 SD (95%CI 3.08-4.91) increase in age and sex-adjusted AGV Z-score (P < .0001).
    3 context sentences
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.
  5. 05HumanNon-randomized trialSafety outcome

    With longer vosoritide use, 5 children with these growth disorders discontinued medication due to adverse events.

    In plain wordsWith longer vosoritide use, 5 children stopped medication because of adverse events.

    Peptide
    Vosoritide
    Outcome
    Not applicableDiscontinuation due to adverse events
    Study

    n = 30

    Outcome group
    Adverse events · Whole body
    Studied dose
    15 µg/kg/day · subcutaneousAs given in this study (human).

    Measurements

    Subjects discontinuing medication due to adverse events
    5 subjects
    longer use

    Source sentences

    Summary
    However, with longer use, 5 subjects discontinued medication due to adverse events, including 3 slipped capital femoral epiphyses and 4 cases of genu valgum.
    3 context sentences
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.
  6. 06HumanNon-randomized trialSafety outcome

    With longer vosoritide use in children with these growth disorders, adverse events included 3 slipped capital femoral epiphyses.

    In plain wordsWith longer vosoritide use, adverse events included 3 slipped capital femoral epiphyses in children with these growth disorders.

    Peptide
    Vosoritide
    Outcome
    Not applicableSlipped capital femoral epiphysis
    Study

    n = 30

    Outcome group
    Adverse events · Musculoskeletal
    Studied dose
    15 µg/kg/day · subcutaneousAs given in this study (human).

    Measurements

    Slipped capital femoral epiphyses among adverse events
    3 events
    longer use

    Source sentences

    Summary
    However, with longer use, 5 subjects discontinued medication due to adverse events, including 3 slipped capital femoral epiphyses and 4 cases of genu valgum.
    3 context sentences
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.
  7. 07HumanNon-randomized trialSafety outcome

    With longer vosoritide use in children with these growth disorders, adverse events included 4 cases of genu valgum.

    In plain wordsWith longer vosoritide use, adverse events included 4 cases of inward knee angulation in children with these growth disorders.

    Peptide
    Vosoritide
    Outcome
    Not applicableGenu valgum
    Study

    n = 30

    Outcome group
    Adverse events · Musculoskeletal
    Studied dose
    15 µg/kg/day · subcutaneousAs given in this study (human).

    Measurements

    Genu valgum among adverse events
    4 cases
    longer use

    Source sentences

    Summary
    However, with longer use, 5 subjects discontinued medication due to adverse events, including 3 slipped capital femoral epiphyses and 4 cases of genu valgum.
    3 context sentences
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.
  8. 08HumanNon-randomized trialEfficacy outcome

    In children with RASopathies, ACAN or NPR2 deficiency, AGV increased during vosoritide treatment in all genetic subgroups.

    In plain wordsIn children with these growth disorders, growth velocity increased during vosoritide treatment in all genetic subgroups.

    Peptide
    Vosoritide
    Outcome
    IncreaseAGV across genetic subgroups
    Study

    n: not reported in source

    Comparator
    Observation period
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    15 µg/kg/day · subcutaneous · 12 monthsAs given in this study (human).

    Source sentences

    Summary
    The increase in AGV was seen in all genetic subgroups.
    3 context sentences
    Summary · context
    Prospective Phase 2 basket trial.
    Summary · context
    Thirty prepubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height ≤ -2.25 SD.
    Summary · context
    Six-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 µg/kg/day.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:37 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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