Achondroplasia - Pipeline Insight, 2024

This “Achondroplasia - Pipeline Insight, 2024” report provides comprehensive insights about 5+ companies and 5+ pipeline drugs in Achondroplasia pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered

• Global coverage

Achondroplasia Understanding

Achondroplasia: Overview

chondroplasia (also called: ACH, Achondroplasia Dwarfism) is the most commonly occurring abnormality of bone growth (skeletal dysplasia) and is a form of short-limbed dwarfism. The word for word translation of ‘Achondroplasia’ is “without cartilage formation.” Cartilage is a robust but flexible tissue that makes up much of the skeleton during early development. However, in Achondroplasia the problem is not in forming cartilage but in converting it to bone (a process called ossification), especially in the long bones of the arms and legs. This condition is similar to another skeletal disorder called Hypochondroplasia, but the features of Achondroplasia tend to be more severe.

Symptoms of Achondroplasia
The characteristic features of Achondroplasia include::

• An average-size trunk
• Short arms and legs with particularly short upper arms and thighs
• Limited range of motion at the elbows
• An enlarged head (macrocephaly) with a prominent forehead
• Fingers that are typically short; the ring finger and middle finger may diverge, giving a hand a three-pronged (trident) appearance.

The health problems commonly associated with Achondroplasia include::

• Episodes in which breathing slows or stops for short periods (apnea)
• Obesity
• Recurrent ear infections.

Causes of Achondroplasia
Achondroplasia is caused by a gene alteration (mutation) in the FGFR3 gene. The FGFR3 gene makes a protein called fibroblast growth factor receptor 3 that is involved in converting cartilage to bone. FGFR3 is the only gene known to be associated with Achondroplasia.

The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of Achondroplasia. Researchers believe that these mutations cause the FGFR3 protein to be overly active, which interferes with skeletal development and leads to the disturbances in bone growth seen with this disorder.

In approximately 80% of patients, Achondroplasia occurs as a result of a spontaneous genetic mutation; and in the remaining 20%, it is inherited from a parent.

Treatment of Achondroplasia
Currently, there is no way to prevent or treat Achondroplasia, since the majority of cases result from unexpected new mutations. Treatment with growth hormone does not substantially affect the height of an individual with Achondroplasia. Leg-lengthening surgeries may be considered in some particular cases. Detection of bone abnormalities, particularly in the back, is important to prevent breathing difficulties and leg pain or loss of function. Kyphosis (or hunch-back) may need to be surgically corrected if it does not disappear when the child begins walking. Surgery may also help in the treatment of bowing of legs. Ear infections need to be treated immediately to avoid the risk of hearing loss. Dental problems may need to be addressed by an orthodontist (a dentist with specialized training in the alignment of teeth). Children born with Achondroplasia need to have their height, weight, and head circumference monitored using special growth curves standardized for Achondroplasia. Measures to avoid obesity at an early age are recommended.

Achondroplasia Emerging Drugs Chapters

This segment of the Achondroplasia report encloses its detailed analysis of various drugs in different stages of clinical development, including phase III, II, I and preclinical. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.

Achondroplasia Emerging Drugs

BMN-111: BioMarin PharmaceuticalBioMarin has developed BMN-111 (vosoritide), an investigational drug derived from a natural human peptide that is a positive regulator of bone growth. Vosoritide binds to a specific receptor, which initiates intracellular signals that inhibit the overactive FGFR3 pathway. The investigational treatment is being studied in children with Achondroplasia under the age of 18 because their bones are still amenable to growth.

Infigratinib: QED Therapeutics (BridgeBio)Infigratinib (previously known as BGJ398) is an investigational, orally-administered, ATP-competitive, FGFR1-3 tyrosine kinase inhibitor therapy in development for the treatment of patients with FGFR-driven diseases, including cholangiocarcinoma (bile duct cancer), urothelial carcinoma (bladder cancer), and Achondroplasia, a bone growth disorder in children; Infigratinib is not chemotherapy.

QED Therapeutics holds worldwide rights to evaluate its safety and efficacy for multiple FGFR-driven diseases.

TA-46: PfizerTA-46 (Recifercept) is an investigational, soluble recombinant human fibroblast growth factor receptor 3 (FGFR3) decoy, a mechanism of action that is believed to normalize the overactive FGFR3 signaling pathways that underlie bone development abnormalities associated with Achondroplasia. Therachon was developing TA-46 as a weekly subcutaneous injection for children and adolescents living with the condition. However, In May 2019, Pfizer has entered into a definitive agreement to acquire all the shares of Therachon Holding with assets in development for the treatment of Achondroplasia. TA-46 has completed Phase I and has received Orphan Drug Designation from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Preclinical data in the mouse model show the ability of TA-46 to restore bone growth and metabolism defects that are associated with Achondroplasia. The Phase I clinical trial started in 2018 and the first participant has already been dosed. In Phase I clinical trials healthy participants are dosed with the drug (in this case TA-46), so no therapeutic effect is expected from this trial, where the objective is to assess if the drug is safe to administer in a patient and its pharmacokinetics.

CNP-ELP: PhaseBio Pharmaceuticals
PhaseBio Pharmaceuticals is developing CNP-ELP for the treatment of Achondroplasia. At present, it is in the preclinical stage of development. The C-type natriuretic peptide, or CNP, is a regulator of bone growth and can rescue defects in fibroblast growth factor 3 that cause Achondroplasia resulting in dwarfism. Native CNP has a half-life of less than 3 min, limiting its use as a direct therapeutic. CNP-ELP product candidate is being developed to deliver therapeutic levels of CNP with once-weekly subcutaneous injections. In a mouse model, they observed a demonstrated effect on linear growth when the CNP-ELP product candidate was injected once every 4 days.

Achondroplasia: Therapeutic Assessment

This segment of the report provides insights about the different Achondroplasia drugs segregated based on following parameters that define the scope of the report, such as:

Major Players in Achondroplasia

There are approx. 6+ key companies which are developing the therapies for Achondroplasia. The companies which have their Achondroplasia drug candidates in the most advanced stage, i.e. Phase III include, BioMarin Pharmaceutical.

Phases

This report covers around 5+ products under different phases of clinical development like

• Late stage products (Pre-registration and Phase III)
• Mid-stage products (Phase II and Phase I/II) and
• Early-stage products (Phase I) along with the details of
• Pre-clinical and Discovery stage candidates
• Discontinued & Inactive candidates

Route of Administration

Achondroplasia pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as

• Oral
• Subcutaneous etc.

Molecule Type

Products have been categorized under various Molecule types such as

• Natriuretic peptides
• Recombinant fusion proteins
• Small molecule

Achondroplasia: Pipeline Development Activities

The report provides insights into different therapeutic candidates in phase III, II, I and preclinical stage. It also analyses Achondroplasia therapeutic drugs key players involved in developing key drugs.

Pipeline Development Activities

The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Achondroplasia drugs.

Report Highlights

• The companies and academics are working to assess challenges and seek opportunities that could influence Achondroplasia R&D. The therapies under development are focused on novel approaches to treat/improve Achondroplasia.
• In April 2020, BioMarin Pharmaceutical announced that based on recent meetings with health authorities in the US and Europe, the Company plans to submit marketing applications to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the third quarter of 2020 for vosoritide.
• In June 2018, BioMarin Pharmaceutical announced that the company dosed the first participant in a global Phase II study for vosoritide, an analog of C-type Natriuretic Peptide (CNP), in infants and young children with Achondroplasia, the most common form of disproportionate short stature in humans.
• In June 2019, BioMarin Pharmaceutical announced that the New England Journal of Medicine (NEJM) published online results from a Phase II dose-finding and extension study for vosoritide in children with Achondroplasia. The data demonstrated that vosoritide was generally well tolerated with a mild side effect profile and resulted in a sustained increase in annualized growth velocity for up to 42 months in children aged 5-14 years with Achondroplasia, the most common form of disproportionate short stature in humans. The results will also appear in the July 4th printed issue.
• In February 2019, Ascendis Pharma announced that the US Food and Drug Administration (FDA) had granted Orphan Drug Designation (ODD) to TransCon CNP for children with Achondroplasia.
• In July 2019, Pfizer announced the successful completion of its acquisition of the privately-held clinical-stage biotechnology company Therachon Holding AG. Under the terms of the transaction, Pfizer acquired Therachon for USD 340 million with an additional UDS 470 million in additional payments contingent on the achievement of key milestones in the development and commercialization of TA-46.
• In June 2017, Therachon announced that the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) had granted Orphan Drug Designation to TA-46 for the treatment of patients with Achondroplasia, the most common form of short-limbed dwarfism.
• In January 2013, orphan designation was granted by the European Commission to BioMarin Europe Ltd, United Kingdom, for modified recombinant human C-type natriuretic peptide for the treatment of achondroplasia. It has also has received orphan drug designation from the US FDA.
• TransCon CNP received Orphan Drug Designation (ODD) for the treatment of ACH from the FDA in 2019.

Achondroplasia Report Insights

• Achondroplasia Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

Achondroplasia Report Assessment

• Pipeline Product Profiles
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing Achondroplasia drugs?
• How many Achondroplasia drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Achondroplasia?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Achondroplasia therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for Achondroplasia and their status?
• What are the key designations that have been granted to the emerging drugs?

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