Pipeline and Clinical Development Programs

Skeletal Conditions

Trial phase

Product (Trial)

Condition

Technology

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-205 [Canopy ACH-2 EXT])

Trial Status Active, Not Recruiting

Condition

Achondroplasia

Technology

Peptide

Title

A Study to Evaluate Long-Term Safety, Tolerability, and Efficacy of BMN 111 in Children With Achondroplasia (ACH)

Study Description

This Phase 2, open-label, extension study evaluates the long-term safety, tolerability, and efficacy of BMN 111 (vosoritide) in children with achondroplasia.

Primary Outcome Measure*

Incidence of treatment-emergent adverse events

Select Inclusion Criteria*

Have completed 24 months of vosoritide treatment in Study 111-202
Parent/guardian provides informed written consent if required
If sexually active, must be willing to use a highly effective method of contraception while participating in the study

Secondary Outcome Measures*

Annualized growth velocity
Height standard score

Select Exclusion Criteria*

Requires any investigational agent prior to completion of study period
Have a condition or circumstance that places the subject at high risk during this study

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT02724228

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-208 [Canopy ACH-2I EXT])

Trial Status Active, Not Recruiting

Condition

Achondroplasia

Technology

Peptide

Title

An Extension Study to Evaluate Safety and Efficacy of BMN 111 in Children With Achondroplasia

Study Description

This Phase 2, open-label, multicenter, long-term extension study, with approximately 70 subjects, evaluates the safety and efficacy of BMN 111 (vosoritide) in children with achondroplasia until subjects reach near-adult final height.

Primary Outcome Measures*

Evaluate the incidence of treatment-emergent adverse events
Evaluate change in height/length z-score in children with ACH treated with vosoritide

Select Inclusion Criteria*

Must have completed Study 111-206 on investigational treatment
Parent/guardian provides informed written consent if required

Secondary Outcome Measures*

Evaluate the change from baseline in mean annualized growth velocity
Characterize maximum concentration

Select Exclusion Criteria*

Permanently discontinued vosoritide or placebo prior to completion of Study 111-206
Have a clinically significant finding or arrhythmia on ECG that indicates abnormal cardiac function or conduction or QTc-F >450 msec

* Additional measures/criteria may apply.
ACH, achondroplasia; ECG, electrocardiogram; QTcF, corrected QT interval by Fridericia.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT03989947

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-209 [Canopy ACH-2H])

Trial Status Active, Not Recruiting

Condition

Achondroplasia

Technology

Peptide

Title

A Clinical Trial to Evaluate Safety of Vosoritide in At-risk Infants With Achondroplasia

Study Description

This is a Phase 2 randomized, open-label clinical trial of BMN 111 (vosoritide) in infants and young children with a diagnosis of achondroplasia at a heightened risk of requiring cervicomedullary decompression surgery.

Primary Outcome Measure*

Incidence of treatment-emergent adverse events

Select Inclusion Criteria*

Parent/guardian provides informed written consent if required
Have ACH, documented by genetic testing

Secondary Outcome Measure*

Evaluate the effect of vosoritide on total foramen magnum volume

Select Exclusion Criteria*

Have hypochondroplasia or short-stature condition other than achondroplasia
Have CMC that either does not require surgical intervention or does require immediate surgical intervention

* Additional measures/criteria may apply.
ACH, achondroplasia; CMC, cervicomedullary compression.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT04554940

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-302 [Canopy ACH-3 EXT])

Trial Status Active, Not Recruiting

Condition

Achondroplasia

Technology

Peptide

Title

An Extension Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia

Study Description

This Phase 3, open-label, long-term extension study is intended and designed to assess BMN 111 (vosoritide) as a therapeutic option for the treatment of children with achondroplasia.

Primary Outcome Measure*

Change from baseline in mean annualized growth velocity

Select Inclusion Criteria*

Must have completed Study 111-301
Females ≥10 years old, or those with menses, need negative pregnancy tests at baseline and during the study

Secondary Outcome Measures*

Changes in health-related quality of life
Potential changes in daily activity performance
Characterize maximum concentration of vosoritide in plasma

Select Exclusion Criteria*

Permanently discontinued vosoritide or placebo prior to completion of Study 111-301
Have a clinically significant finding that indicates abnormal cardiac function
Evidence of slowed growth of at least 6 months or closed growth plates in lower extremity X-rays

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT03424018

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-603 [Acorn])

Trial Status Recruiting

Condition

Achondroplasia

Technology

Peptide

Title

A multicentre, non-interventional study to evaluate long-term safety in patients with achondroplasia treated with Voxzogo (vosoritide)

Study Description

This post-authorization safety study will evaluate the long-term safety of treatment with vosoritide in patients with achondroplasia in a real-world setting.

Primary Outcome Measure*

Exposure-adjusted incidence rate of all new bone-related safety events of interest which have not previously been observed in patients

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit EMA.Europa.eu EUPAS47514

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-605 [VISTA])

Trial Status Recruiting

Condition

Achondroplasia

Technology

Peptide

Title

A Participant-mediated Observational Virtual Registry of Children With Achondroplasia in the United States (VISTA)

Study Description

This is an observational study of a pediatric cohort with achondroplasia in the United States. This cohort consists of both individuals treated and untreated with vosoritide.

Primary Outcome Measure*

Height, weight, body mass index, head circumference, annualized grown velocity, surgical procedures and/or medical interventions by age

Select Inclusion Criteria*

Physician diagnosis of achondroplasia
Age at time of enrollment
Receiving medical care in the United States

Secondary Outcome Measure*

Not applicable

Select Exclusion Criteria*

Lack of any medical records

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06168201

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-210 [Canopy ISS-2])

Trial Status Recruiting

Condition

Idiopathic Short Stature

Technology

Peptide

Title

A Phase 2 Study of Vosoritide in Children With Idiopathic Short Stature

Study Description

This study will evaluate the effect of multiple doses of vosoritide and the effect of vosoritide compared to human growth hormone (hGH), in children with Idiopathic Short Stature.

Primary Outcome Measure*

Change in annualized growth velocity (AGV), height, and height Z-score

Select Inclusion Criteria*

Patients > 3 and ≤ 9 (female) or ≤ 10 (males) years of age
Height Z-score ≤-2.25 standard deviations compared to age and sex matched population norms
Tanner Stage 1 (unless too young to stage)

Secondary Outcome Measures*

Incidence of adverse events
Change in pharmacodynamic parameters (urine cyclic guanine monophosphate, serum collagen X marker)
Pharmacokinetics of vosoritide

Select Exclusion Criteria*

Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to: Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome)
History of treatment with a growth promoting agent

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06382155

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Idiopathic Short Stature

(111-903 [Canopy ISS-OS])

Trial Status Recruiting

Condition

Idiopathic Short Stature

Technology

Observational

Title

A Study to Assess Growth in Children With Idiopathic Short Stature

Study Description

This study will collect growth measurements and other variables of interest to generate baseline growth data in children with Idiopathic Short Stature.

Primary Outcome Measure*

Change in growth (annualized growth velocity, height Z-score, height) and anthropometric measures (body mass index [BMI], BMI Z-score)

Select Inclusion Criteria*

Patients > 2 and ≤ 14 (female) or ≤ 16 (males) years of age
Height Z-score ≤-2.5 standard deviations compared to age and sex matched population norms

Secondary Outcome Measures*

Rates of medical events of interest
Association between specific variants and growth velocity

Select Exclusion Criteria*

Presence of pituitary hormone deficiencies
Bone age advanced over chronological age by >3 years
Received an investigational product or medical device within last 6 months

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06309979

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-211 [Canopy NS, TS, SHOX-D-2])

Trial Status Recruiting

Condition

Turner Syndrome, SHOX Deficiency and Noonan Syndrome

Technology

Peptide

Title

A Phase 2 Basket Study of Vosoritide in Children with Turner Syndrome, SHOX Deficiency and Noonan Syndrome with an Inadequate Response to Human Growth Hormone

Study Description

This study in children with Turner syndrome, SHOX deficiency, and Noonan syndrome will evaluate the effect of 3 doses of vosoritide versus human growth hormone (hGH) on growth. The long-term efficacy and safety of vosoritide at the therapeutic dose will be evaluated up to final adult height.

Primary Outcome Measure*

Change from baseline in annualized growth velocity (AGV)

Select Inclusion Criteria*

Patients ≥ 3 years old, and < 10 years old (females) or < 11 years old (males)
Height Z-score ≤ -2 standard deviations in reference to the general population of the same age and sex
Have been receiving continuous human growth hormone (hGH) for the treatment of short stature associated with their condition for a minimum of 1 year immediately prior to enrollment

Secondary Outcome Measures*

Change from baseline in height, height Z-score, and height up to final adult height (FAH)
Incidence of adverse events

Select Exclusion Criteria*

Patients with Turner syndrome known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia
Bone age advanced beyond chronological age by more than 2 years
Evidence of decreased growth velocity (AGV < 1.5 cm/year) as assessed over a period of at least 6 months and growth plate closure assessed using bilateral lower extremity X-rays

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06668805

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-212 [Canopy HCH-2I])

Trial Status Recruiting

Condition

Hypochondroplasia

Technology

Peptide

Title

A Study of Vosoritide Versus Placebo in Children With Hypochondroplasia Aged 0 to < 36 Months

Study Description

The purpose of this study is to evaluate the safety and efficacy of daily administration of vosoritide in participants with Hypochondroplasia aged 0 to < 36 months over a 52-week period.

Primary Outcome Measures*

Incidence of treatment-emergent adverse events and serious adverse events
Change from baseline in standard clinical laboratory values (hematology, urinalysis, and chemistry), heart rate, respiratory rate, temperature, blood pressure, and height Z-score

Select Inclusion Criteria*

0 to < 36 months of age
Weight at Day 1 visit (pre-treatment) ≥3 kg
Have a confirmed genetic diagnosis of HCH (obtained via whole genome sequencing; presence of a FGFR3 pathogenic variant associated with HCH)

Secondary Outcome Measures*

Change in height
Cumulative annualized growth velocity (AGV)
6-month interval AGV
Change from baseline in upper to lower body segment ratio
Change from baseline in arm span

Select Exclusion Criteria*

Short stature condition other than HCH
Have an unstable medical condition likely to require surgical intervention during the study period
Have been treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time
Have used any other investigational product or investigational medical device for the treatment of HCH or short stature at any time

* Additional measures/criteria may apply.
HCH, Hypochondroplasia;

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT07126262

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-303 [Canopy HCH-3])

Trial Status Active, Not Recruiting

Condition

Hypochondroplasia

Technology

Peptide

Title

Interventional Study of Vosoritide for the Treatment of Children With Hypochondroplasia

Study Description

The intent and design of this Phase 3 study is to assess vosoritide as a therapeutic option for the treatment of children with hypochondroplasia (HCH).

Primary Outcome Measure*

Change from baseline in annualized growth velocity (AGV)

Select Inclusion Criteria*

Patients ≥ 3 to < 18 years of age
Confirmed genetic diagnosis of HCH
A height Z score of ≤-2 standard deviations in reference to the general population of the same age and sex, as calculated using the Center for Disease Control and Prevention (CDC) growth charts

Secondary Outcome Measure*

Change from baseline in standing height and height Z-score

Select Exclusion Criteria*

Have an unstable condition likely to require surgical intervention during the study
Evidence of decreased growth velocity and/or growth plate closure
Treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids
Planned or expected to have limb-lengthening surgery or bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction) during the study period

* Additional measures/criteria may apply.
HCH, hypochondroplasia.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06455059

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Vosoritide

(111-308 [Canopy HCH-3 EXT])

Trial Status Enrolling by Invitation

Condition

Hypochondroplasia

Technology

Peptide

Title

Long-Term Extension Study of Vosoritide to Treat Children With Hypochondroplasia (CANOPY-HCH-EXT)

Study Description

The purpose of this study is to evaluate the long-term safety and efficacy of daily doses of vosoritide in participants with HCH

Primary Outcome Measure*

Change from baseline in height Z-score

Select Inclusion Criteria*

Completed the Week 52 visit for Study 111-303 or 111-212 and have open epiphyses as assessed by left hand antero-posterior (AP) X-rays
Females ≥ 10 years old or who have begun menses must have a negative pregnancy test at the Baseline visit and be willing to have additional pregnancy tests during the study
If sexually active, participants must be willing to use a highly effective method of contraception while participating in the study

Secondary Outcome Measures*

Change from baseline in height
Absolute 6- or 12-month interval AGV
Change from baseline in upper to lower body segment ratio
Change from baseline in Quality of Life In Short-Statured Youth (QoLISSY) total score

Select Exclusion Criteria*

Permanently discontinued study treatment in Study 111-303 or 111-212
Evidence of decreased growth velocity (AGV <1.5 cm/year) as assessed over a period of at least 6 months and growth plate closure assessed as per standard of care
Planned or expected to have limb-lengthening surgery during the study period
Planned or expected bone-related surgery during the study period

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT07073014

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Hypochondroplasia

(111-809)

Trial Status Not started

Condition

Hypochondroplasia

Technology

Observational

Title

Generating Growth Curves for Standing and Sitting Height in Hypochondroplasia: A Multi-Center Retrospective Natural History Study

Study Description

This study will be a retrospective chart review of height measurements in patients ≤18 years old with a clinically or genetically confirmed diagnosis of hypochondroplasia (HCH)

Primary Outcome Measure*

To develop sex- and age-specific growth curves for height (standing and sitting, as well as lower-to-upper body segment) for patients with HCH

Secondary Outcome Measure*

To calculate sex- and age-specific Z-scores (referenced to Centers for Disease Control and Prevention [CDC] average stature) for height (standing and sitting) in patients with HCH

* Additional measures/criteria may apply.¹²

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Hypochondroplasia

(111-902 [Canopy HCH-OS])

Trial Status Recruiting

Condition

Hypochondroplasia

Technology

Observational

Title

A Multicenter Multinational Observational Study of Children With Hypochondroplasia

Study Description

This study will collect growth measurements and other variables of interest to assess growth and the clinical course of hypochondroplasia over time.

Primary Outcome Measures*

Change in growth (annualized growth velocity, height Z-score, height)
Change in anthropometric measures (body mass index [BMI], upper and lower length ratio, arms spam to standing height ratio)

Select Inclusion Criteria*

Patients ≤ 15 years of age
Genetic confirmation of hypochondroplasia

Secondary Outcome Measures*

Change in quality of life and patient and caregiver assessments of disease severity
Rates of medical events of interest

Select Exclusion Criteria*

Diagnosis of genetic short stature condition other than hypochondroplasia or a genetic variant known to cause another genetic syndrome associated with short stature
Received an investigational product or medical device within the last 6 months

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06212947

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 333

Long-acting CNP

Trial Status Not started

Condition

Achondroplasia, Hypochondroplasia

Technology

Peptide

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Enzyme Therapies

Trial phase

Product (Trial)

Condition

Technology

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-306 [PEGASUS])

Trial Status Active, Not Recruiting

Condition

Phenylketonuria

Technology

Enzyme

Title

Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria (PEGASUS)

Study Description

This is a Phase 3, open-label, randomized, controlled study enrolling approximately 54 adolescents with PKU. The study is designed to assess the safety and efficacy of pegvaliase injections.

Primary Outcome Measures*

Change in blood Phe concentration
Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0

Select Inclusion Criteria*

Must be 12 to 17 years old
Signed informed consent

Secondary Outcome Measure*

Change in total dietary protein intake

Select Exclusion Criteria*

Previous treatment with pegvaliase
Use of any medication that is intended to treat PKU within 14 days prior to administration

* Additional measures/criteria may apply.
CTCAE v5.0, Common Terminology Criteria for Adverse Events version 5.0; Phe, phenylalanine; PKU, phenylketonuria.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT05270837

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-402 [PALLADIUM])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

Enzyme

Title

Rapid Drug Desensitization Study in Adults Experiencing Hypersensitivity Reactions to Palynziq (PALLADIUM)

Study Description

This is a Phase 4 study to evaluate the impact of rapid drug desensitization (RDD) on adult (≥18 years old) participants with PKU who have experienced hypersensitivity reactions (HSRs) leading to treatment interruption or reduction of dose or dosing frequency while receiving commercial Palynziq.

Primary Outcome Measure*

Tolerance, defined as the ability to restart Palynziq at the dose at which the reactive HSR occurred (reactive dose) and escalate as appropriate within 24 weeks following the RDD, without requiring treatment interruption or reduction of dose or dosing frequency due to HSRs; and 2. Reduction in occurrence of HSRs Grade 2 or above within 24 weeks following RDD

Select Inclusion Criteria*

18 years of age or older
Have phenylketonuria and been receiving commercial Palynziq and enrolled in the REMS
Have developed HSRs leading to treatment interruption or reduction of dose or dosing frequency (Grade 2 or above) while on Palynziq, and be able to undergo RDD within 6 weeks from the reactive HSR and last Palynziq dose

Secondary Outcome Measure*

Change in PEG IgG and IgM, PAL IgG and PAL IgM, and C3/C4 from Baseline to after RDD and at Week 24

Select Exclusion Criteria*

Medical Conditions:
Pregnant on the day of the RDD
Uncontrolled asthma, active upper respiratory infection or other active infections, or cardiovascular disease
Prior/Concomitant Therapies:
Not using antihistamine premedication(s) at the time of reactive HSRs
Willing and able to resume and tolerate Palynziq at the reactive dose prior to the RDD
Receiving concurrent injectables containing PEG with the exception of PEG-containing vaccines, such as COVID-19 vaccinations
Receiving beta blockers

* Additional measures/criteria may apply.

REMS, Risk Evaluation & Mitigation Strategy; HSR, Hypersensitivity Reactions; PEG, Polyethylene glycol; PAL, Phenylalanine ammonia lyase; IgG, Immunoglobulin G; IgM, Immunoglobulin M;

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06780332

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-501[PALace])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

Enzyme

Title

A Long-term, Post-marketing Safety Study of Palynziq in Patients With PKU (PALace)

Study Description

This is a 10-year multicenter, global, observational study to further characterize the safety profile of pegvaliase, including hypersensitivity reactions, long-term safety and tolerability, and the effectiveness of the additional risk minimization measures (aRMMs) (European Union [EU] only) in subjects receiving pegvaliase for the treatment of PKU.

Primary Outcome Measure*

To quantify and characterize the risk of protocol-defined safety events in incident-users receiving pegvaliase for the treatment of PKU in a real-world setting

Select Inclusion Criteria*

Documented diagnosis of PKU per local standard of care
Receiving or plan to receive pegvaliase treatment within 30 days of enrollment

Secondary Outcome Measure*

To quantify and characterize the risk of protocol-defined safety events in subjects receiving pegvaliase for the treatment of PKU in a real-world setting

Select Exclusion Criteria*

Subject has any kind of disorder that may compromise the ability of the subject to give written informed consent
Currently participating in an interventional study of any investigational product, device, or procedure

* Additional measures/criteria may apply.
PKU, phenylketonuria.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT05813678

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-503 [PALisade])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

Enzyme

Title

A Long Term, Post-marketing Study of Immune Response in Patients Receiving Palynziq Treatment for PKU (PALisade)

Study Description

This is a 10-year multi-center, prospective, longitudinal, single arm study evaluating immunologic, inflammatory and laboratory parameters associated with long-term Palynziq treatment in subjects with phenylketonuria (PKU) in the United States (US).

Primary Outcome Measure*

Immunologic and inflammatory responses associated with occurrences of: acute systemic hypersensitivity reaction, anaphylaxis, angioedema, serum sickness, severe hypersensitivity reaction, severe or persistent arthralgia, severe injection site reaction

Select Inclusion Criteria*

Enrolled at US sites participating in the 165-501 (PALace) study.

Secondary Outcome Measures*

Immunologic and inflammatory responses (immunologic testing, inflammatory markers) associated with occurrences of end-organ function (e.g., kidney, liver) related, immune-mediated adverse drug reactions
The potential association between immunologic responses and blood Phe levels

Select Exclusion Criteria*

Legal incapacity or limited legal capacity without legal guardian representation
Subject is unable or unwilling to provide informed consent for the additional interventional burden of the study (blood sampling)

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06305234

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-504 [PALomino])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

Enzyme

Title

A Global, Multicenter Study to Assess Maternal, Fetal and Infant Outcomes of Exposure to Palynziq® (Pegvaliase) During Pregnancy and Breastfeeding (PALomino)

Study Description

This is a Phase 4 observational study designed to assess the impact of Palynziq® (pegvaliase) treatment in pregnant women with PKU and on their offspring who were exposed to pegvaliase at any time during pregnancy and breastfeeding.

Primary Outcome Measure*

Pregnancy outcome and infant development for women who have been treated with Palynziq (pegvaliase) within 2 weeks of their last menstrual period

Select Inclusion Criteria*

Subject or legal guardian consent
Confirmation of ongoing pregnancy
Diagnosed with PKU

Secondary Outcome Measures*

Pregnancy outcomes
Serious adverse events
Maternal pegvaliase use during breastfeeding

Select Exclusion Criteria*

Currently participating in a BioMarin-sponsored interventional study

* Additional measures/criteria may apply.
PKU, phenylketonuria.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT05579548

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Cerliponase alfa

(190-501)

Trial Status Active, Not Recruiting

Condition

CLN2 Disease

Technology

Enzyme

Title

Cerliponase Alfa Observational Study in the US

Study Description

This is a multicenter, observational study for patients with a confirmed diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as TPP1 deficiency, who intend to be or are currently being treated with cerliponase alfa.

Primary Outcome Measure*

To evaluate the long-term safety of cerliponase alfa in patients with neuronal ceroid lipofuscinosis type 2

Select Inclusion Criteria*

Diagnosed with CLN2 disease
Currently receiving or plan to begin treatment with cerliponase alfa
Parent/guardian provides informed written consent if required

Secondary Outcome Measures*

Hypersensitivity
Impact of severe adverse events on motor and language functions

Select Exclusion Criteria*

Currently receiving treatment in another investigational device or drug study

* Additional measures/criteria may apply.
CLN2, late infantile neuronal ceroid lipofuscinosis type 2; TPP1, tripeptidyl peptidase 1

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT04476862

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Cerliponase alfa

(190-504)

Trial Status Recruiting

Condition

CLN2 Disease

Technology

Enzyme

Title

Cerliponase Alfa Observational Study

Study Description

To evaluate long-term safety of cerliponase alfa in patients with neuronal ceroid lipofuscinosis Type 2 (CLN2 disease).

* Additional measures/criteria may apply.
CLN2, late infantile neuronal ceroid lipofuscinosis type 2;

For reference and comprehensive trial information, visit EMA.Europa.eu EUPAS29031

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Hemophilia

Trial phase

Product (Trial)

Condition

Technology

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Valoctocogene roxaparvovec-rvox

(270-205 [GENEr8-INH])

Trial Status Active, Not Recruiting

Condition

Hemophilia A

Technology

Gene Therapy

Title

Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors

Study Description

This Phase 1/2 clinical study will evaluate the safety and efficacy of valoctocogene-roxaparvovec-rvox (BMN 270) in patients with severe hemophilia A and inhibitors to FVIII. Part A of the study will include subjects who have active inhibitors to FVIII, and Part B will include subjects with a prior history of inhibitors.

Primary Outcome Measure*

Treatment-related adverse events over 60 months

Select Inclusion Criteria*

Males ≥18 years of age with hemophilia A
Documented prior residual FVIII activity ≤1 IU/dL

Secondary Outcome Measures*

Change in median FVIII activity
Change in FVIII inhibiter titer
Absence of recurrence of FVIII inhibitors

Select Exclusion Criteria*

Detectable pre-existing antibodies to the AAV5 capsid
Active infection or immunosuppressive disorder (patients with HIV and undetectable viral load are not excluded)
Receiving immune tolerance induction therapy or prophylaxis with FVIII (Part A only)

* Additional measures/criteria may apply.
AAV, adeno-associated virus; FVIII, factor VIII; HIV, human immunodeficiency virus.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT04684940

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Valoctocogene roxaparvovec-rvox

(270-304 [GENEr8-JPN)

Trial Status Active, Not Recruiting

Condition

Hemophilia A

Technology

Gene Therapy

Title

Phase 3 Study for Efficacy and Safety Outcomes Data in Japanese Patients With Severe Hemophilia A (GENEr8-JPN)

Study Description

This Phase 3 clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in Japanese patients with severe hemophilia A.

Primary Outcome Measure*

Change from baseline in FVIII activity

Select Inclusion Criteria*

Japanese males ≥18 years of age with hemophilia A
Residual FVIII levels ≤1 IU/dL

Secondary Outcome Measures*

Change from baseline in utilization of FVIII replacement therapy
Change from baseline in number of bleeding episodes requiring FVIII replacement treatment

Select Exclusion Criteria*

Detectable pre-existing antibodies to the AAV5 capsid
Active infection or any immunosuppressive disorder, including HIV infection
Significant liver dysfunction

* Additional measures/criteria may apply.
AAV, adeno-associated virus; FVIII, factor VIII; HIV, human immunodeficiency virus.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06224907

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Valoctocogene roxaparvovec-rvox

(270-401 [GENEr8-LTE])

Trial Status Enrolling by Invitation

Condition

Hemophilia A

Technology

Gene Therapy

Title

A Long-Term Follow-Up Study in Severe Hemophilia A Subjects Who Received BMN 270 in a Prior BioMarin Clinical Trial (270-401)

Study Description

The BMN 270 (valoctocogene-roxaparvovec-rvox) clinical development program consists of multiple interventional studies designed to assess the safety and efficacy of a single infusion of valoctocogene-roxaparvovec-rvox for at least 5 years post-infusion. This long-term follow-up study is needed to help further understand the long-term safety of valoctocogene-roxaparvovec-rvox beyond 5 years and to assess the durability of efficacy.

Primary Outcome Measure*

Evaluate the long-term safety of valoctocogene-roxaparvovec-rvox

Select Inclusion Criteria*

Subjects must have completed their primary treatment study
Subjects must be capable of giving signed informed consent

Secondary Outcome Measures*

Evaluate the long-term effects of valoctocogene-roxaparvovec-rvox in subjects with hemophilia A previously treated in a BioMarin clinical trial
Evaluate the use of hemostatic agents

Select Exclusion Criteria*

Subjects must enroll in Study 270-401 within 4 months of the date of that study completion visit
Subjects must be healthy and not have a condition that would interfere with interpretation of the study

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT05768386

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Valoctocogene roxaparvovec-rvox

(270-601 [GENEr8-COAS])

Trial Status Not started

Condition

Hemophilia A

Technology

Gene Therapy

Title

GENEr8-COAS: A Non-Interventional, Multi-National, Longitudinal Study of Patients Treated with Roctavian (valoctocogene roxaparvovec)

Study Description

This study is a non-interventional, multi national, longitudinal cohort study will describe the bleeding profile and long-term durability of coagulation factor VIII (FVIII) expression in subjects administered with Roctavian.

Select Inclusion Criteria*

Diagnosed with HA and treated with Roctavian. Patients will be offered the opportunity to enroll in this study only after a clinical decision has been made that they will receive Roctavian, however, only subjects who are eventually administered Roctavian will be included in the analysis.

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit EMA.Europa.eu EUPAS49071

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Valoctocogene roxaparvovec-rvox

(270-801 [GENEr8-GTR])

Trial Status Recruiting

Condition

Hemophilia A

Technology

Gene Therapy

Title

GENEr8-GTR: A Retrospective Cohort Study of Patients Treated with Roctavian(valoctocogene roxaparvovec): An Analysis of Patient Registries

Study Description

This study is being undertaken to better characterize the long-term effectiveness and safety outcomes of patients treated with Roctavian in a real-world setting

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit EMA.Europa.eu EUPAS49243

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Innovation

Trial phase

Product (Trial)

Condition

Technology

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 401
(formerly INZ-701)

(701-007 [PROPEL])

Trial Status Recruiting

Condition

ENPP1 Deficiency, ABCC6 Deficiency

Technology

Enzyme

Title

PROPEL – A Prospective Observational Patient Registry to Evaluate ENPP1 and ABCC6 Deficiency

Study Description

The purpose of this prospective registry is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase1(ENPP1) Deficiency and the infantile-onset form of adenosine triphosphate (ATP) binding cassette transporter protein subfamily C member 6 (ABCC6) Deficiency longitudinally.

Primary Outcome Measure*

Assessments will be collected during each subject’s routine visit. The assessments will be done per local standard of care.
- Assessment of Patient Functional changes through a validated Patient Reported Outcomes (PROs) tools.*
- Assessment of Health-Related Quality-of-Life (HRQoL) changes through validated PROs tools.*
- Measurement of inorganic phosphate (PPi) levels in patients’ venous blood.*

Select Inclusion Criteria*

Agree to provide access to relevant medical records
One of the following genetic or clinical criteria:
- A confirmed prenatal or postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (i.e., homozygous or compound heterozygous)
- A confirmed monoallelic ENPP1 mutation with clinical symptoms
- A confirmed prenatal or postnatal molecular genetic diagnosis of ABCC6 Deficiency with biallelic mutations

Secondary Outcome Measure*

Not applicable

Select Exclusion Criteria*

Patients who are currently participating in an BMN 401 (INZ-701) interventional clinical study.

* Additional measures/criteria may apply.; All PROs and PPi sampling are optional.

For comprehensive trial information, visit ClinicalTrials.gov NCT06302439

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 401
(formerly INZ-701)

(701-104 [ENERGY])

Trial Status Recruiting

Condition

ENPP1 Deficiency, ABCC6 Deficiency

Technology

Enzyme

Title

Title
The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency

Study Description

Study Description
The primary purpose of this study is to assess the safety and tolerability of INZ-701 in infants with ENPP1 Deficiency or with ABCC6 Deficiency

Primary Outcome Measures*

Number of Treatment Emergent Adverse Events
Incidence of Anti-Drug Antibodies
Left Ventricular Ejection Fraction

Select Inclusion Criteria*

Confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency or ABCC6 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous)
Have clinical manifestations of Generalized Arterial Calcification of Infancy (GACI) or GACI-2, which may include, but are not limited to, pathologic ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly
<1 year of age at Baseline (Day 1)
Weigh ≥0.5 kg at the time of the first dose of INZ-701

Secondary Outcome Measures*

Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels
Area under the Plasma Concentration versus Time Curve (AUC)
Maximum Plasma Concentration (Cmax)

Select Exclusion Criteria*

Care has been withdrawn or study participant is receiving end of life care or hospice only
Known malignancy
Receipt of any non-Inozyme investigational new drug within 5 half-lives of the last dose of the other investigational product or within 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device, through completion of participation in the study

* Additional measures/criteria may apply.

For comprehensive trial information, visit ClinicalTrials.gov NCT05734196

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 401
(formerly INZ-701)

(701-106 [ENERGY3])

Trial Status Active, Not Recruiting

Condition

ENPP1 Deficiency

Technology

Enzyme

Title

The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency

Study Description

The primary purpose of this study is to assess the efficacy and safety of INZ-701 in children with ENPP1 Deficiency

Primary Outcome Measure*

Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration

Select Inclusion Criteria*

Confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous)
≥1 year and <13 years of age at Study Day 1
Open growth plates of the distal femur and proximal tibia in both legs
Plasma Inorganic Pyrophosphate (PPi) concentration of <1400 nM
25-hydroxyvitamin D (25[OH]D) levels of ≥12 ng/mL

Secondary Outcome Measures*

Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score
Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score
Change from Baseline in growth Z-score (height/body length and weight)

Select Exclusion Criteria*

Receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (>5 mg prednisone equivalent per day), anti-fibroblast growth factor 23 (FGF23), and oral and/or IV bisphosphonates
Unable or unwilling to discontinue calcitriol or other active forms of vitamin D3 (or analogs) within 7 days prior to Study Day 1 and/or oral phosphate supplements within 36 hours prior to Study Day 1 if randomized to the INZ-701 arm
Planned orthopedic surgery that may confound the interpretation of study results during the Randomized Treatment Period
Concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives of the last dose or within 4 weeks prior to Randomization, whichever is longer, or use of an investigational device

* Additional measures/criteria may apply.

For comprehensive trial information, visit ClinicalTrials.gov NCT06046820

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 401
(formerly INZ-701)

(701-304 [ADAPT])

Trial Status Active, Not Recruiting

Condition

ENPP1 Deficiency, ABCC6 Deficiency

Technology

Enzyme

Title

ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency

Study Description

The purpose of this study is to assess the long-term safety of INZ-701 in patients with ENPP1 Deficiency or ABCC6 Deficiency who have received INZ-701 in an existing clinical study and choose to continue dosing for the potential treatment of their condition

Primary Outcome Measures*

Number of Treatment Emergent Adverse Events
Incidence of Anti-Drug Antibodies

Select Inclusion Criteria*

>1 year of age
Completed the protocol-required safety and pharmacokinetic/pharmacodynamic and/or efficacy period(s) of a previous INZ-701 clinical study in ENPP1 or ABCC6 Deficiency
Females of childbearing potential who are sexually active must be using or agree to use 1 highly effective form of contraception (per CTFG 2020) from at least 1 month before the first dose of INZ-701 through 30 days after last dose of INZ-701 (greater than 5 half-lives of INZ-701); participants must agree to not donate ova from the period following the first dose of INZ-701 through 30 days after the last dose of INZ-701
Males who are sexually active must agree to use condoms from the period following the first dose of INZ-701 through 30 days after the last dose of INZ-701; participants must agree to not donate sperm from the period following the first dose of INZ-701 through 30 days after last dose of INZ-701

Secondary Outcome Measures*

Mean change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentratio
Time to maximum serum concentration (Tmax)
Maximum Plasma Concentration (Cmax)

Select Exclusion Criteria*

Concurrent participation in another interventional clinical study and/or has received an investigational drug other than INZ-701 within 5 half-lives or within 4 weeks prior to the first dose of INZ-701 in this study, whichever is longer, or use of an investigational device
Pregnant, trying to become pregnant, or breastfeeding
Males trying to father a child

* Additional measures/criteria may apply.

For comprehensive trial information, visit ClinicalTrials.gov NCT06462547

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 351

(351-201)

Trial Status Recruiting

Condition

Duchenne Muscular Dystrophy

Technology

Antisense Oligonucleotide

Title

A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMN 351 in Participants With Duchenne Muscular Dystrophy

Study Description

This Phase 1/2 clinical study will evaluate the safety and tolerability of BMN 351 in patients with Duchenne Muscular Dystrophy (DMD) with a genetic mutation amenable to exon 51 skipping.

Primary Outcome Measure*

Incidence of adverse and serious adverse events with BMN 351

Select Inclusion Criteria*

Ambulatory patients 4-10 years of age
Diagnosis of DMD with a mutation amenable to exon 51 skipping

Secondary Outcome Measure*

Pharmacokinetic (PK) concentrations of BMN 351 in plasma, urine and muscle

Select Exclusion Criteria*

History of gene therapy treatment
Use of exon skipping therapy within 12 weeks prior to first visit

* Additional measures/criteria may apply.
DMD, duchenne muscular dystrophy.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06280209

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4