The purpose of this study is to evaluate i) the effect of multiple doses of vosoritide and ii) the effect of the therapeutic dose of vosoritide compared to human growth hormone (hGH), in children with idiopathic short stature (ISS).

Start Date01 Sep 2024

Sponsor / Collaborator

BioMarin Pharmaceutical, Inc.

NCT06455059 / Enrolling by invitationPhase 3

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vosoritide in Children With Hypochondroplasia

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).

Start Date01 Jun 2024

Sponsor / Collaborator

BioMarin Pharmaceutical, Inc.

NCT05849389 / RecruitingPhase 2IIT

Vosoritide for Treatment of Short Stature in Girls With Turner Syndrome

Turner syndrome (TS) is characterized by a missing whole or part of the second sex chromosome in a phenotypic female, resulting in short stature due to haploinsufficiency of the short-stature homeobox-containing (SHOX) gene. Growth hormone (GH) is an approved therapy for this condition, although not associated with GH deficiency, and benefits are modest. Vosoritide, a C-type natriuretic peptide (CNP) analog, targets chondrocytes within the growth plate leading to increased cell proliferation and hypertrophy. We hypothesize that patients with TS and short stature will respond to vosoritide treatment leading to increased growth velocity. This study will enroll pre-pubertal girls with TS who are either naïve to GH or have had a poor response to GH therapy. All subjects will be treated with vosoritide for 12 months and will be assessed for safety monitoring and improvement in height outcomes. Annualized growth velocity (AGV) on vosoritide will be compared to AGV in the 6-18 months prior to initiation of vosoritide based on historical data available in the medical record. Subjects with a positive response to therapy will be given the option to continue in the extension phase of the study during which they will continue to receive vosoritide until growth cessation.

Start Date01 Mar 2024

Sponsor / Collaborator-

100 Clinical Results associated with Vosoritide

100 Translational Medicine associated with Vosoritide

100 Patents (Medical) associated with Vosoritide

Literatures (Medical) associated with Vosoritide

Deutsches Arzteblatt international

The treatment of growth disorders in childhood and adolescence

Review

Author: Binder, Gerhard ; Schnabel, Dirk ; Woelfle, Joachim

BACKGROUND:

3% of all children are unusually short, and 3% are unusually tall. New approaches have broadened the range of therapeutic options in treating growth disorders.

METHODS:

This review is based on publications retrieved by a selective review of the literature and on the authors' clinical experience.

RESULTS:

Pituitary growth hormone deficiency is treated with recombinant growth hormone. Long-acting preparations of this type became available recently, but their long-term safety and efficacy are still unknown. Vosoritide, a CNP analogue, has also been approved for the treatment of achondroplasia, and severe primary deficiency of insulin-like growth factor 1 (IGF-1) can be treated with recombinant IGF-1. In the treatment of excessively tall stature, new information on the safety of growth-attenuating treatment and an altered perception of above-average height in society have led to a change in management.

CONCLUSION:

There are new options for the treatment of rare causes of short stature, while new information on the safety of treatment strategies for excessive tallness have led to a reconsideration of surgical intervention. There is insufficient evidence on the benefits and risks of supraphysiological GH therapy and of newer treatment options for which there are as yet no robust data on adult height. Therefore, before any treatment is provided, physicians should give patients and their families detailed information and discuss their expectations from treatment and the goals that treatment can be expected to achieve.

01 Jan 2024·Advances in therapy

Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice

Article

Author: Faden, Maha ; Deyle, David ; Hartmann, Gabriele ; Semler, Oliver ; Huser, Aaron J ; Wilcox, William R ; Bober, Michael B ; Hoover-Fong, Julie ; Sousa, Sérgio B ; Rutsch, Frank ; Travessa, Andre M ; Legare, Janet M ; Lausch, Ekkehart ; Verardo, Angela ; White, Klane K ; Smith, Pamela ; Rohrer, Tilman R ; Mohnike, Klaus ; Carroll, Ricki ; Cormier-Daire, Valérie

INTRODUCTION:

Vosoritide is the first precision medical therapy approved to increase growth velocity in children with achondroplasia. Sharing early prescribing experiences across different regions could provide a framework for developing practical guidance for the real-world use of vosoritide.

METHODS:

Two meetings were held to gather insight and early experience from experts in Europe, the Middle East, and the USA. The group comprised geneticists, pediatric endocrinologists, pediatricians, and orthopedic surgeons. Current practices and considerations for vosoritide were discussed, including administration practicalities, assessments, and how to manage expectations.

RESULTS:

A crucial step in the management of achondroplasia is to determine if adequate multidisciplinary support is in place. Training for families is essential, including practical information on administration of vosoritide, and how to recognize and manage injection-site reactions. Advocated techniques include establishing a routine, empowering patients by allowing them to choose injection sites, and managing pain. Patients may discontinue vosoritide if they cannot tolerate daily injections or are invited to participate in a clinical trial. Clinicians in Europe and the Middle East emphasized the importance of assessing adherence to daily injections, as non-adherence may impact response and reimbursement. Protocols for monitoring patients receiving vosoritide may be influenced by regional differences in reimbursement and healthcare systems. Core assessments may include pubertal staging, anthropometry, radiography to confirm open physes, the review of adverse events, and discussion of concomitant or new medications-but timing of these assessments may also differ regionally and vary across institutions. Patients and families should be informed that response to vosoritide can vary in both magnitude and timing. Keeping families informed regarding vosoritide clinical trial data is encouraged.

CONCLUSION:

The early real-world experience with vosoritide is generally positive. Sharing these insights is important to increase understanding of the practicalities of treatment with vosoritide in the clinical setting.

01 Jan 2024·The Lancet. Child & adolescent health

Vosoritide therapy in children with achondroplasia aged 3−59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial

Article

Author: Mochizuki, Hiroshi ; Bacino, Carlos A ; Han, Lynn ; Irving, Melita ; Tofts, Louise ; Savarirayan, Ravi ; Polgreen, Lynda E ; Qi, Yulan ; Harmatz, Paul ; Bober, Michael B ; Kotani, Yumiko ; Saal, Howard M ; Fisheleva, Elena ; Ozono, Keiichi ; Basel, Donald ; Charrow, Joel ; Arundel, Paul ; Day, Jonathan ; Wilcox, William R ; Huntsman-Labed, Alice ; Army, Clare ; Jeha, George ; Phillips, John

BACKGROUND:

Vosoritide is a recombinant C-type natriuretic peptide analogue that increases annualised growth velocity in children with achondroplasia aged 5-18 years. We aimed to assess the safety and efficacy of vosoritide in infants and children younger than 5 years.

METHODS:

This double-blind, randomised, placebo-controlled, phase 2 trial was done in 16 hospitals across Australia, Japan, the UK, and the USA. Children younger than 60 months with a clinical diagnosis of achondroplasia confirmed by genetic testing and who had completed a baseline growth study or observation period were enrolled into one of three sequential cohorts based on age at screening: 24-59 months (cohort 1); 6-23 months (cohort 2); and 0-5 months (cohort 3). Each cohort included sentinels who received vosoritide to determine appropriate daily drug dose, with the remainder randomly assigned (1:1) within each age stratum (except in Japan, where participants were randomly assigned within each cohort) to receive daily subcutaneous injections of vosoritide (30·0 μg/kg for infants aged 0-23 months; 15·0 μg/kg for children aged 24-59 months) or placebo for 52 weeks. Participants, caregivers, investigators, and the sponsor were masked to treatment assignment. The first primary outcome was safety and tolerability, assessed in all participants who received at least one study dose. The second primary outcome was change in height Z score at 52 weeks from baseline, analysed in all randomly assigned participants. This trial is registered with EudraCT, 2016-003826-18, and ClinicalTrials.gov, NCT03583697.

FINDINGS:

Between May 13, 2018, and March 1, 2021, 75 participants were recruited (37 [49%] females). 11 were assigned as sentinels, whereas 32 were randomly assigned to receive vosoritide and 32 placebo. Two participants discontinued treatment and the study: one in the vosoritide group (death) and one in the placebo group (withdrawal). Adverse events occurred in all 75 (100%) participants (annual rate 204·5 adverse events per patient in the vosoritide group and 73·6 per patient in the placebo group), most of which were transient injection-site reactions and injection-site erythema. Serious adverse events occurred in three (7%) participants in the vosoritide group (decreased oxygen saturation, respiratory syncytial virus bronchiolitis and sudden infant death syndrome, and pneumonia) and six (19%) participants in the placebo group (petit mal epilepsy, autism, gastroenteritis, vomiting and parainfluenza virus infection, respiratory distress, and skull fracture and otitis media). The least-squares mean difference for change from baseline in height Z score between the vosoritide and placebo groups was 0·25 (95% CI -0·02 to 0·53).

INTERPRETATION:

Children with achondroplasia aged 3-59 months receiving vosoritide for 52 weeks had a mild adverse event profile and gain in the change in height Z score from baseline.

FUNDING:

BioMarin Pharmaceutical.

News (Medical) associated with Vosoritide

17 Jun 2024

·www.biospace.com

BioMarin to Present Data Highlighting Significant Impact of VOXZOGO® (vosoritide) in Bone Health and Health-Related Quality of Life in Achondroplasia at 2024 International Conference on Children's Bone Health

New Investigator-Led Study Shows VOXZOGO Significantly Increased Bone Length While Maintaining Bone Strength Through 5 Years of Observation in Children with Achondroplasia Phase 2 and 3 Data on VOXZOGO Demonstrate Safety, Efficacy and Impact on Proportionality and Health-Related Quality of Life for Children with Achondroplasia New Research Underscores Unmet Medical Needs of People with Hypochondroplasia SAN RAFAEL, Calif., June 17, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced the presentation of new data from an investigator-led analysis of the Phase 2 111-205 study, which demonstrate that children with achondroplasia treated with VOXZOGO® experienced increases in bone length while maintaining bone strength. The data will be presented at the 11th International Conference on Children's Bone Health (ICCBH) in Salzburg, Austria, June 22-25, 2024. BioMarin will also share the first results from a study underscoring the unmet medical needs of people living with hypochondroplasia. "With thousands of children treated since approval, the breadth and depth of data collected from our trials demonstrate VOXZOGO's safety and benefit in children of all ages, including those under 5 who have received VOXZOGO for up to four years," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "CNP is emerging as a natural and holistic regulator of statural development, and safety and efficacy data presented to date illustrate VOXZOGO's positive impact on bone growth, proportionality and quality of life. Based on this extensive evidence, we are accelerating the development of VOXZOGO across a multitude of growth-related conditions with significant unmet need." Significant Impact on Bone Length, Strength, Proportionality and Health-Related Quality of Life in Achondroplasia Results from an investigator-led analysis of BioMarin's Phase 2 111-205 study found that children who received VOXZOGO (n=30) had significant increases in bone length and metacarpal cortical area after approximately five years of therapy, suggesting that treatment allowed the bone to remain strong as it lengthened. "In order for children with achondroplasia to experience meaningful changes in daily functioning following treatment to enable growth, it is critical that bone robustness is maintained to preserve strength," said Cathleen Raggio, M.D., a pediatric orthopedic surgeon at the Hospital for Special Surgery in New York. "With this study, for the first time we have shown that treatment with VOXZOGO enabled bones to remain strong as they lengthened, which is promising as we continue to better understand the impact of this therapeutic advancement." Additional data to be presented at ICCBH, previously shared at the 2024 Pediatric Endocrine Society Annual Meeting, showcase VOXZOGO's efficacy, safety and impact on health-related quality of life in children with achondroplasia. Data observed in the Phase 3 111-301 and 111-302 studies suggest that VOXZOGO can have the potential to improve health-related quality of life among children with achondroplasia, particularly in aspects associated with physical functioning, an outcome of significant importance for children and families impacted by achondroplasia. Phase 2 and Phase 3 data also demonstrated consistent positive effects on linear growth and improvement in proportionality in children of all ages with growth potential, with follow-up conducted up to four years after the initiation of VOXZOGO treatment. Safety results were consistent with the well-characterized safety pro VOXZOGO. Data Underscore Unmet Needs in Hypochondroplasia Data from a retrospective, real-world matched cohort study using electronic medical records from England showed that comorbidity event rates (e.g., respiratory, cardiovascular, orthopedic and mental health-related events) were higher in people living with hypochondroplasia (n=610) compared to people living without the condition (n=2440). General practitioner visits (median annual visits = 11.2 vs. 5.4, risk ratio [RR] = 1.8), hospital in-patient admissions (RR=5.5) and average length of hospital stay (5.6 vs. 3.8 days) were all greater as well. Most people evaluated in the study were aged 16-65 at the start of follow up. These data suggest there is a significant burden of disease amongst people of all ages with hypochondroplasia, highlighting the need for proactive management and linkage to care. VOXZOGO Clinical Development Program Milestones Building on its leadership in achondroplasia, BioMarin has several clinical trials underway for hypochondroplasia, idiopathic short stature (ISS) and other growth-related conditions. A multinational observational study in children with hypochondroplasia (111-902) is currently recruiting participants, and the first patient is on track to be dosed in the treatment phase (Phase 3 trial) in June with enrollment completion expected in early 2025. The company's observational study in children with ISS (111-903) has begun enrolling patients, and the Phase 2 treatment arm will also begin enrollment later this year (111-210). Additionally, a study in multiple other genetic short stature conditions, including Turner syndrome, SHOX deficiency, and Noonan syndrome, is anticipated to begin enrollment later this year. Key presentations at ICCBH are listed below, with all times in Central European Summer Time (CEST): Oral Presentations Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia is Accompanied by Improvement in Physical Aspects of Quality of Life Oral #OC4.3 Monday, June 24, 2024, 3:45 – 4:45 p.m. A Promising Adjuvant Treatment for Growing Mice with Moderate-to-Severe Osteogenesis Imperfecta: A Pilot Study of a CNP Analog Oral #OC5.3 Tuesday, June 25, 2024, 1:30 – 2 p.m. Poster Presentations Does Vosoritide Treatment Affect Bone Strength in Children with Achondroplasia? Poster #P151 Sunday, June 23, 2024, 12 – 1 p.m. Persistence of Growth Promoting Effects in Infants and Toddlers with Achondroplasia: Results from a Phase 2 Extension Study with Vosoritide Poster #P79 Sunday, June 23, 2024, 12 – 1 p.m. Design and Objectives of the Acorn Study: A Non-Interventional Study Evaluating Long-Term Safety in Achondroplasia Children Treated with Vosoritide Poster #P91 Sunday, June 23, 2024, 12 – 1 p.m. Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia for up to 4 Years: Update from Phase 3 Extension Study Poster #P78 Monday, June 24, 2024, 12 – 1 p.m. Comorbidity and Mortality Burden Among Patients with Hypochondroplasia in England between 1998-2019 Poster #P176 Monday, June 24, 2024, 12 – 1 p.m. About VOXZOGO In children with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in FGFR3. VOXZOGO, a C-type natriuretic peptide (CNP) analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth. VOXZOGO is approved in the U.S. and Japan to increase linear growth in children of all ages with achondroplasia with open epiphyses, and VOXZOGO is indicated in the EU for the treatment of achondroplasia in children 4 months of age and older whose epiphyses are not closed, as confirmed by appropriate genetic testing. In the U.S., this indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s). To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history. To date, more than 3,000 people with achondroplasia around the world have received VOXZOGO. In total, VOXZOGO is available in 43 markets worldwide. Patient Support Accessing VOXZOGO To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-833-VOXZOGO (1-833-869-9646) or e-mail VOXZOGOSupport@biomarin-rareconnections.com. For more information about VOXZOGO, please visit . For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. About Achondroplasia Achondroplasia is a rare genetic growth-related condition caused by a variation in the FGFR3 gene. It is characterized by disproportionate short stature and a potentially high burden of complications related to impaired endochondral bone growth. Approximately 80% of children with achondroplasia are born to parents of average stature as a result of a spontaneous variation in the FGFR3 gene. The worldwide incidence of achondroplasia is around one in 25,000 live births. VOXZOGO U.S. Important Safety Information What is VOXZOGO used for? VOXZOGO is a prescription medicine used to increase linear growth in children with achondroplasia and open growth plates (epiphyses). VOXZOGO is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. What is the most important safety information about VOXZOGO? VOXZOGO may cause serious side effects including a temporary decrease in blood pressure in some patients. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, feeling tired, or nausea), patients should eat a meal and drink 8 to 10 ounces of fluid within 1 hour before receiving VOXZOGO. What are the most common side effects of VOXZOGO? The most common side effects of VOXZOGO include injection site reactions (including redness, itching, swelling, bruising, rash, hives, and injection site pain), high levels of blood alkaline phosphatase shown in blood tests, vomiting, joint pain, decreased blood pressure, and stomachache. These are not all the possible side effects of VOXZOGO. Ask your healthcare provider for medical advice about side effects, and about any side effects that bother the patient or that do not go away. How is VOXZOGO taken? VOXZOGO is taken daily as an injection given under the skin, administered by a caregiver after a healthcare provider determines the caregiver is able to administer VOXZOGO. Do not try to inject VOXZOGO until you have been shown the right way by your healthcare provider. VOXZOGO is supplied with Instructions for Use that describe the steps for preparing, injecting, and disposing VOXZOGO. Caregivers should review the Instructions for Use for guidance and any time they receive a refill of VOXZOGO in case any changes have been made. Inject VOXZOGO 1 time every day, at about the same time each day. If a dose of VOXZOGO is missed, it can be given within 12 hours from the missed dose. After 12 hours, skip the missed dose and administer the next daily dose as usual. The dose of VOXZOGO is based on body weight. Your healthcare provider will adjust the dose based on changes in weight following regular check-ups. Your healthcare provider will monitor the patient's growth and tell you when to stop taking VOXZOGO if they determine the patient is no longer able to grow. Stop administering VOXZOGO if instructed by your healthcare provider. What should you tell the doctor before or during taking VOXZOGO? Tell your doctor about all of the patient's medical conditions including If the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine). If the patient has kidney problems or renal impairment. If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby. If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk. Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. You may report side effects to BioMarin at 1-866-906-6100. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please see additional safety information in the full Prescribing Information and Patient Information. About BioMarin Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of the genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, please visit . Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: data to be presented at the 11th International Conference on Children's Bone Health (ICCBH), including the oral and poster presentations; the development of BioMarin's VOXZOGO program generally; VOXZOGO's efficacy, safety and impact on health-related quality of life in children with achondroplasia, including impact on bone length, strength and health-related quality of life; the potential benefits of VOXZOGO for children with growth-related conditions beyond achondroplasia, including hypochondroplasia and idiopathic short stature; potential unmet needs in hypochondroplasia; and the continued clinical development of VOXZOGO, including BioMarin's plans for clinical trials for hypochondroplasia, idiopathic short stature and other growth-related conditions. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned pre-clinical studies and clinical trials of VOXZOGO; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the Food and Drug Administration, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, BioMarin RareConnections® and VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc. Company Codes: NASDAQ-NMS:BMRN

Clinical ResultPhase 2Phase 3Drug Approval

04 Jun 2024

·www.fiercebiotech.com

BridgeBio dwarfism drug increases height in children, beating BioMarin's Voxzogo

BridgeBio is sufficiently encouraged by 12- and 18-month data on daily oral FGFR3 inhibitor infigratinib to expand development. BridgeBio Pharma has bounced back from the withdrawal of infigratinib in oncology, linking the molecule to a BioMarin-beating height increase in children with a growth disorder in a midphase clinical trial. The FDA withdrew accelerated approval of infigratinib in May, completing a process that began one year earlier when BridgeBio’s then-partner Helsinn asked the agency to pull the authorization. Helsinn made the request after struggling to enroll subjects for a required confirmatory clinical trial. As the cancer program went off the rails, BridgeBio continued to advance low-dose infigratinib in a form of dwarfism. BridgeBio reported top-line data from the midphase PROPEL 2 trial in March 2023 and followed up with six-month data around one year ago. Tuesday, the biotech unwrapped 12- and 18-month data that add to evidence that the daily oral FGFR3 inhibitor infigratinib may have an edge over BioMarin’s approved dwarfism therapy Voxzogo. On infigratinib, children with achondroplasia, the most common type of dwarfism, had mean increases in annualized height velocity (AHV) of 2.51 cm/year after 12 months and 2.50 cm/year after 18 months. The FDA approved (PDF) Voxzogo on the basis of a trial that reported a 1.40 cm/year increase in AHV at 12 months. BridgeBio also shared data on a secondary endpoint. The ratio of the upper to lower body improved in children on infigratinib, falling from 2.02 at baseline to 1.88 after 18 months. The 0.14 improvement is greater than the change BioMarin reported across two years of follow up. Ravi Savarirayan, M.D., Ph.D., of Murdoch Children’s Research Institute, said in a statement that changes in body ratio are encouraging and suggest infigratinib “has the potential to enhance functionality for people living with achondroplasia in addition to increasing growth.” Infigratinib appears capable of beating Voxzogo, with the usual caveats about cross-trial comparisons, but its effect on AHV fell between the six- and 12-month updates. After six months, the mean increase in AHV was 3.38 cm/year from baseline. Even so, with no patients having treatment-related adverse events, BridgeBio is sufficiently encouraged by the data to expand development. A phase 3 study in achondroplasia is already underway and on track to complete enrollment by the end of the year. BridgeBio is now working to enter phase 3 in hypochondroplasia, a form of short-limbed dwarfism. After talking to regulators, BridgeBio has begun a small, open-label phase 2 trial in hypochondroplasia. The study will test infigratinib at one dose, the level that has shown most promise in achondroplasia, to support progression into a placebo-controlled registrational phase 3 study in hypochondroplasia. Last month, BioMarin said it aimed to start a phase 3 trial in hypochondroplasia by midyear. BioMarin reported a 74% increase in Voxzogo revenue in the first quarter, causing sales of the product to reach $153 million, but multiple companies are aiming to challenge the biotech for the achondroplasia market. Ascendis Pharma and Sanofi are among the drug developers with achondroplasia assets in the clinic.

Clinical ResultPhase 3Drug ApprovalAccelerated Approval

04 Jun 2024

·firstwordpharma.com

BridgeBio's growth disorder drug tops expectations in Phase II update

BridgeBio Pharma's investigational therapy infigratinib surpassed expectations in the latest readout of the Phase II PROPEL 2 study, demonstrating sustained and statistically significant increases in annualised height velocity (AHV) in children with achondroplasia.In Cohort 5 of the study, which evaluated the highest dose of 0.25 mg/kg per day, the oral FGFR3 inhibitor resulted in a mean change from baseline of +2.51 cm/year in AHV at 12 months, and a change of +2.50 cm/year at the 18-month mark.'Best-in-class data'Analysts were anticipating only a 2-cm improvement, according to Salim Syed of Mizuho Securities. While growth did slow between the sixth and twelfth months, he said that "the question was regarding its potential magnitude… Today's reported best-in-class data should settle any debate on this."Syed pointed out that body proportions also improved. At month 18, there was a statistically significant improvement in the ratio between the upper and lower body segments, with a mean ratio of 1.88 compared to 2.02 at baseline.By contrast, there were no significant improvements in upper/lower body segment ratio in children receiving BioMarin Pharmaceutical's once-daily injection Voxzogo (vosoritide) during its pivotal 52-week study, "so we'd argue that the body proportionality data may represent a point of differentiation from Voxzogo in investor debates," the analyst said.BioMarin's modified C-type natriuretic peptide was first approved in 2021 based on data showing it improved annualised growth velocity by 1.57 cm/year versus placebo. The drug's label was expanded last October to include children under the age of 5.Clean safety profileMeanwhile, infigratinib's safety profile in PROPEL 2 is encouraging as well, with no treatment-related adverse events tied to the drug in any Cohort 5 participant. There were no cases of hyperphosphatemia or hypergrowth either.BridgeBio has also launched a Phase III registrational study, PROPEL 3 that is currently recruiting and is expected to be fully enrolled by year-end. Mizhuo has said it estimates peak sales of $1.2 billion for infigratinib in achondroplasia.

Clinical ResultPhase 3Phase 2Drug Approval

100 Deals associated with Vosoritide

External Link

KEGG	Wiki	ATC	Drug Bank
D11190	Vosoritide	-	DB11928

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Achondroplasia	EU	BioMarin International Ltd.	26 Aug 2021
Achondroplasia	IS	BioMarin International Ltd.	26 Aug 2021
Achondroplasia	LI	BioMarin International Ltd.	26 Aug 2021
Achondroplasia	NO	BioMarin International Ltd.	26 Aug 2021

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hypochondroplasia	Phase 3	US	BioMarin Pharmaceutical, Inc.	01 Jun 2024
Hypochondroplasia	Phase 3	AU	BioMarin Pharmaceutical, Inc.	01 Jun 2024
Idiopathic short stature	Phase 2	-	BioMarin Pharmaceutical, Inc.	01 Sep 2024
Dwarfism	Phase 2	US	-	04 Aug 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03989947 (Study 111-206, PRNewswire) Manual	Phase 2	Achondroplasia	-	VOXZOGO	zjjrlmfjtp(uzzrazbspj) = gajefkbism ezbzrjukww (kanswjseqv, 0.46-1.93) View more	Positive	20 Oct 2023
111-208 (ESPE2023)	Phase 2	Achondroplasia	34	Vosoritide 15 mg/kg	kiypdnnamj(owugydlxbk) = pmashwxfbx pepsmyhtvj (rxkqoburhy, 2.98 - 9.56)	Positive	21 Sep 2023
ESPE2022	Phase 2	Diabetic macular oedema \| Noonan Syndrome NPR2 mutations \| PTPN11 mutations	6	Vosoritide 15 mg/kg/day	jfkdsgptdm(mzszrheawx) = ayluaghabq hukkuezgqx (iyntiabazs )	Positive	15 Sep 2022
ATU (ESPE2022)	Not Applicable	Achondroplasia	29	Vosoritide	jgcdptktku(fktxikyhye) = The majority of AEs were mild and included injection site reactions and vomiting, with the most common being injection site rash (4 events) stuipwqosd (rwzzhzssse ) View more	Positive	15 Sep 2022
ESPE2022	Phase 2	Hypochondroplasia	26	Vosoritide	dabeoxlrcd(frlvfqldtz) = phbpmvmjba mqabkukyoa (mvwillauaa, 6.8 - 8)	-	15 Sep 2022
NCT03583697 (Corporate Publications) Manual	Phase 2	Achondroplasia	75	vosoritide	tscvmgfbrf(qbyokatefn) = brvuoqyhgi colhhuazsy (nglsczurrh, 0.07 - 0.54) View more	Positive	13 Jun 2022
NCT03583697 (Corporate Publications) Manual	Phase 2	Achondroplasia	75	Placebo	uvovtltent(mnfjmxbgia) = ybsentjaow aeaycuqxro (iopichwyjn )	Positive	13 Jun 2022
NCT03197766 (CTgov)	Phase 3	Achondroplasia	121	Placebo	txoyzimcxm(jdqkpdxwvb) = nxpqcevbbi zqashrlcek (rbjpsocqhj, mssknnknga - lmplnnyqsg) View more	-	02 Mar 2022
NCT03424018 (Pubmed \| Genet Med) Manual	Phase 3	Achondroplasia	119	Vosoritide	ogjcxwlatb(oceimthono) = fhbxfkppyr lrvlskonkr (itaixbtxsg ) View more	Positive	01 Dec 2021
NCT03424018 (Pubmed \| Genet Med) Manual	Phase 3	Achondroplasia	119	Placebo	ogjcxwlatb(oceimthono) = vixhsmwvqx lrvlskonkr (itaixbtxsg ) View more	Positive	01 Dec 2021
NCT03197766 (Pubmed) Manual	Phase 3	Achondroplasia	121	vosoritide	nqexrxogzg(meelczdkbr): difference = 1.57 (95% CI, 1.22 - 1.93), P-Value = <0.0001 View more	Positive	05 Sep 2020
NCT03197766 (Pubmed) Manual	Phase 3	Achondroplasia	121	Placebo		Positive	05 Sep 2020
Phase 2 Clinical Trial (ESPE2018)	Phase 2	Achondroplasia FGFR3 \| C-type natriuretic peptide (CNP) \| urine cGMP	35	Vosoritide 2.5 μg/kg	mplhjffowg(cgktyqikuo) = czrxtlrolt kyokalmngn (lztxwmffvv, 2.275)	Positive	27 Sep 2018
Phase 2 Clinical Trial (ESPE2018)	Phase 2		35	Vosoritide 15 μg/kg	mplhjffowg(cgktyqikuo) = ohsxkzmpyl kyokalmngn (lztxwmffvv, 1.873)	Positive	27 Sep 2018

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