Beyond Achondroplasia

Growing together with Clara

August 15, 2018
by inesp.alves

QED Tx – a new company working on a treatment for achondroplasia

At the beginning of 2018, QED Therapeutics was launched by Bridge Bio, as a new biotechnology company, focused on precision medicine for FGFR-driven diseases.

1. What are FGFRs?

The fibroblast growth factor receptors (FGFRs) regulate important biological processes including cell proliferation (multiplication) and differentiation during development and tissue repair. Over the past decades, numerous pathological conditions and developmental syndromes have emerged as a consequence of deregulation in the FGFRs signaling network. The human fibroblast growth factor receptor (FGFR) family comprises of four family members—FGFR1, FGFR2, FGFR3 and FGFR4. (1)

Achondroplasia is caused by a heterozygous mutation in the fibroblast growth factor receptor-3 gene (FGFR3) on chromosome 4p16.3. (2)

The lead candidate of QED Tx is Infigratinib (BGJ398), that is an orally administered tyrosine kinase inhibitor that blocks FGFR1-FGFR2-FGFR3. It has shown meaningful clinical activity in patients in the oncology/cancer area, specifically with chemotherapy-refractory cholangiocarcinoma FGF2 fusions and metastatic urothelial carcinoma with FGFR3 genomic alterations. (3)

With the research by Kombla-Ebri D et al., 2016Infigratinib demonstrated also potential in pediatric skeletal dysplasias, including achondroplasia. In this investigation, researchers demonstrated that low doses of infigratinib corrected pathological hallmarks of achondroplasia in mouse models. (4)

In May 2016, it was already published here in Beyond Achondroplasia, a review on NVP-BGJ398: “New inhibitor of FGFR3 in a mouse model“. NVP-BGJ398 is the same as BGJ398 or Infigratinib. So, to learn more deeply about this compound, read the previous review from 2016. (5)


QED Therapeutics acquired the worldwide rights to infigratinib from Novartis (NVP) for use in all applications and will develop the compound as a treatment for multiple FGFR-driven diseases, including cancers and achondroplasia.

What is precision Medicine?

Is an approach when healthcare is individually tailored on the basis of a person’s genes, lifestyle, and environment. Advances in genetics and the growing availability of health data present an opportunity to make precise personalized patient care a clinical reality. Precision medicine is powered by patient data. The health records and genetic codes of patients and healthy volunteers are vital, and help people to influence their own health care and the direction of research. (6)

Stage of clinical studies with Infigratinib

Infigratinib is currently under study in a Phase 2 trial for the treatment of chemotherapy-refractory cholangiocarcinoma (bile duct cancer) with FGFR2 fusions and other activating genomic alterations. (3)

QED is currently evaluating infigratinib in preclinical studies for the treatment of achondroplasia including further efficacy studies and a robust safety program. Pending results from this program, the company intend to begin clinical studies with infigratinib in patients with achondroplasia in 2019.



  1. Tiong K et al., Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers, Apoptosis. 2013; 18(12): 1447–1468.
  2. OMIN –
  3. QED Therapeutics –
  4. Kombla-Ebri D et al.Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model, J Clin Invest. 2016 May 2; 126(5): 1871–1884
  5. Beyond Achondroplasia –
  6. Hodson R, Precision medicine, Nature volume537, pageS49 (08 September 2016)



August 6, 2018
by inesp.alves

Update: Focus groups with teenagers and parents- in the USA

There are updates for the new study to understand achondroplasia organized by Global Perspectives and will be conducted by ICON, a contract research organization, on behalf of a pharmaceutical company.

This study has the purpose to:

  1. Understand the impact of achondroplasia on daily life activities,
  2. Understand opinions on possible treatments and how treatment decisions are made
  3. Get feedback on a draft survey designed for a future study

Image 1 – Get to know your people through focus groups. Credits: Faithful Citizen


Requested participants

  • Individuals living in the USA and willing to travel to New York
  • Individuals with achondroplasia with ages between 13 and 17 years old and one parent

Dates and location

This will be held during one day over a weekend in New York, USA, on 8th September. Participants will be invited to participate in an in-person focus group day, consisting of three discussions (each lasting 90 minutes).


Participants will be compensated for their time and for their daily life expertise in achondroplasia with an amount of $450 ($900 per family). All travel expenses will be covered.


Invitation to participation

Sonia López, Global Perspectives Senior Project Manager invitation letter:

My name is Sonia López and I work at Global Perspectives, an international Market Research agency specialized in healthcare.

I was wondering if you would be interested or know anyone who would be interested in the paid study below.

We are currently looking for parents of children with achondroplasia to take part in 3 discussion groups in New York or eventually remotely.  Eligible participants will be compensated (insert incentive amount) for their time.

This is an exciting opportunity to provide insights directly to researchers who are interested in understanding more about living with achondroplasia. The purpose of the study is to understand the impact of achondroplasia on daily life activities.

If you are interested or would like to receive further information on this study, please feel free to contact me at


Sonia López


Important note

The pharmaceutical company will not receive any identifying information about the participants in this study, and any information provided by the participants as a part of the study will be reported in a way that protects privacy. There will be no medical treatment being provided as part of this study.

July 16, 2018
by inesp.alves

Meclozine for achondroplasia heading to clinical trial

In February 2015, Matsushita et al., published “Meclozine Promotes Longitudinal Skeletal Growth in Transgenic Mice with Achondroplasia Carrying a Gain-of-Function Mutation in the FGFR3 Gene” (here in a short report in Beyond Achondroplasia) and shortly after in 2015, the same team also published “Meclozine as potential effects on short stature and foramen magnum stenosis in transgenic mice with achondroplasia“, that is discussed in the post “Talking with Prof. Matsushita” in Beyond Achondroplasia

The Japanese team from Nagoya University that conducted these studies on meclozine for achondroplasia, early observed that the mice with achondroplasia treated for 3 weeks with 0,4mg/kg meclizine/meclozine once a day, had an estimated annual growth rate of 4 cm growth/year. (1)

More, the team observed an increase in the global length (vertebrae in the spine) as well as the increase of the bone lengths of the radius, ulna (arm bones), femur, tibia (leg bones) and reduced bony bridges around foramen magnum, what is related to cervicomedullary stenosis.(1)

And they also observed restored proportionality in these mice with achondroplasia after the 3 weeks of treatment with meclozine. Is relevant to take into account that the lifespan of a lab mouse is around 40 weeks. (1)

So, 3 years after the first publication, the team anticipates the clinical trial start date to be the 30th July 2018, and it will be conducted in Japan, at Nagoya University Hospital.


Following the information available in the official site UMIN-CTR Clinical Trial: (3)

Official scientific title of the study Safety and pharmacokinetics of meclizine hydrochloride for achondroplasia children
Title of the study (Brief title) Safety and pharmacokinetics of meclizine


Narrative objectives1 Examination of safety as well as 24-hour pharmacokinetics and accumulation at 1 week after a single dose of meclizine.
Basic objectives2 Safety

Pharmacokinetics (PK) is the study of the time course of drug absorption, distribution, metabolism,
and excretion. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Primary goals of clinical pharmacokinetics include
enhancing efficacy and decreasing toxicity of a patient’s drug therapy. (3)

Primary outcomes
  • 24-hour pharmacokinetics of meclizine
  • drug accumulation
  • adverse events and side effects
Key secondary outcomes Simulation of pharmacokinetics in the repeated administration of meclizine for 14 days

The primary outcomes are the immediate goals of this study, that is the Pharmacokinetics of meclizine in the children bodies.

Age-lower limit
5 years-old <=
Age-upper limit
11 years-old >
Gender Male and Female
Key inclusion criteria achondroplasia children
Key exclusion criteria body weight of less than 11 kg
Target sample size 12

Meclozine for achondroplasia – Phase 1 clinical trial 

The phase 1 will include 6 children that will take a single dose of Meclozine/meclizine (25mg/day). The team predicts to run a double dose study with the administration of 50mg/day (25mg twice per day) in other 6 children at the end of the year.

This is a critical study to evaluate the safety of Meclizine in young children.

Meclozine is already available in the market under several brand names, for the treatment of motion sickness, vertigo, nausea, and vomiting in adults and in children over 12 years old (5). But once there is no information of the use of meclozine in children under 12 years-old but is available adult PK data, now is required to know the PK for children. This is the reason why in this study, the phase 1 will include directly children and not healthy adults as like in another clinical trial, because the safety in adults is already known.


Example of a commercial brand of meclizine available in the market. Image credits: Phoenix Medical Services


Repurposing drug for rare diseases

This is related to discovering new uses for approved drugs to provide the quickest possible transition from bench to bedside (6), or in other words, reducing the time from the early laboratory investigation until having a drug approved and available in the market for a specific disease.

Why repurposing drugs?

There is a poor success rate (16%) for drugs entering clinical trials, with a development timeline of 12 to 15 years and a jaw-dropping price tag approaching $1 billion, it makes economic sense for drug developers to explore better therapeutic fits for failed drugs. (7)

Meclozine for Achondroplasia – Phase 2

The team will conduct a 14 days administration safety study after this two PK studies (25mg/day and 50 mg/day).


  1. Matsushita M et al., Meclozine Promotes Longitudinal Skeletal Growth in Transgenic Mice with Achondroplasia Carrying a Gain-of-Function Mutation in the FGFR3 Gene, Endocrinology, Volume 156, Issue 2, 1 February 2015, Pages 548–554
  2. Matsushita M et al., Meclozine has potential effects on short stature and foramen magnum stenosis in transgenic mice with achondroplasiaBone Abstracts (2015) 4 OC13
  3. UMIN-CTR clinical trial
  4. Introduction to Pharmacokinetics and Pharmacodynamics, ASHP
  5. Meclizine,
  6. Repurposing drugs, NCATS
  7. Repurposing drugs for rare diseases, Eureka

July 13, 2018
by inesp.alves

A new step forward for TherAchon: the Dreambird study on Achondroplasia

TherAchon is a Biotechnology company that was established in 2014 and focuses on rare diseases. It is developing a drug for achondroplasia in particular: TA-46, which is planned to go onto phase I clinical trials in 2019 [1].

In order to prepare for the clinical trial with TA-46, TherAchon needs to capture many parameters on achondroplasia, as for example, establish how much children with achondroplasia grow each year, or understanding the baseline growth.

Image adapted from Brain for the cure

TherAchon has announced at the end of June that they have started a Natural History study on achondroplasia, called Dreambird.

The Dreambird study will follow-up 200 participants from several sites in Europe, USA and Canada which will evaluate and measure children growth, disease progression, the potential risk of complications related to ACH and protection factors, among other biological parameters for a specific period [2]. Which parameters will be measured, exactly, have not been disclosed yet, but the full details of this study will be available in the Clinical Trials website very soon.

Is important to emphasize that, because the Dreambird study is an observational study, the experimental drug TA-46 will not be administered at any time in this study.

Nevertheless, since one of the objectives of this study, besides providing a better understanding of pediatric achondroplasia, is to establish the baseline growth rates and to identify biomarkers for achondroplasia, it will be mandatory for children to participate in the Dreambird study before being enrolled in the future interventional studies, namely: the phase 2 and 3 of the TA-46 clinical trial.

The age of children to be enrolled in the Dreambird study is from 0 to 10 years old.



June 30, 2018
by inesp.alves

Vosoritide is now in study in children under 5 years old

BioMarin announced on the 14th June 2018, the first administration of BMN 111 to young children with achondroplasia under 5 years old. (1)

This is the BMN 111-206 study, a phase 2 study in Infants and Toddlers.


BioMarin Pharmaceutical logo (PRNewsfoto/BioMarin Pharmaceutical Inc.)


What happens in a Phase 2 study?

The participants have the disease or condition to be treated and can last up to 2 years. The purpose of this phase is to evaluate efficacy and side effects of the drug. On average, just approximately 33% of the drugs in evaluation in phase 2, move to the next phase. (3)

The 111-206 is a randomized, double-blind, placebo-controlled study of vosoritide in approximately 70 infants and young children with achondroplasia for 52 weeks or 1 year. This means that participants have an equal chance of receiving either placebo (an inactive treatment that looks the same as, and is given in the same way as, the investigational therapy but in just saline) or the investigational product BMN 111. It is not known whether placebo or investigational therapy is being administered to prevent bias. (2)

The study will be followed by a subsequent open-label extension. This means that at this time, both researchers and participants will know if they are getting vosoritide or placebo, and at what dose. (1)

Important information

Children in this study will have completed a minimum three-month baseline study to determine their respective baseline growth prior to entering the Phase 2 study. This differs from the phase 2 study, BMN 111-202, that requested at least 6-month of pretreatment growth assessment in Study 111-901 before study entry, and one standing height at least 6 months prior to screening for 111-202. (4)

This trial is opening in Australia, Japan, the United Kingdom and the United States and participants
must remain a resident of the country they enrolled in throughout the trial period. (2)

Main goals of this 111-206 study

The main objectives of the study are to evaluate the safety, tolerability, and the effect of vosoritide on height Z-scores, which is the number of standard deviations in relation to the mean height of age-matched, average stature children.

Credits (5)


The company also plans to augment the height Z-score data with assessments including proportionality, functionality, quality of life, sleep apnea, and foramen magnum dimension, as well as the advent of major illnesses and surgeries. (1)

One of the major goals to achieve in a treatment for achondroplasia is exactly what said in the previous paragraph, but rationally, this is a big challenge. Let’s wait for the next results and data publication on Vosoritide in children under 5 years-old, in whom effects of the drug are expected to be more evident.



June 9, 2018
by inesp.alves

A way to contribute to the knowledge on achondroplasia

An ongoing study on pediatric achondroplasia conducted by the Brod Group is still enroling participants

Call for participation – USA residents

  • Parents with ACH with children with achondroplasia under 18 years-old
  • children with ACH, with ages between 9 to 11 years-old

You can get more information about this study in this post.

Honorarium for spent time

$125 honorarium for participating in a focus group and a $75 honorarium for participating in a telephone interview


If you are interested in participating, please contact Jane Beck, Senior Research Associate with The Brod Group:


telephone: (415) 317-3987

June 5, 2018
by inesp.alves

A documentary on the lengthening process

The documentary  “The Lucas´s Journey“, by the film director Juan Enis, was produced by the mother of Lucas in 2015 and tells about the lengthening process of a boy with achondroplasia with 15 years-old, that had a total height of 1.25 meters. He decided to undergo this process, facing a long and painful postoperative time. Some images can be harsh to sensitive people.

The documentary wan now the Personal category of the 2018 ALPE Awards.


May 12, 2018
by inesp.alves

TransCon CNP for achondroplasia starts Phase 1 clinical trial

Ascendis Pharma announced on the 8th May it has dosed the first volunteers in a first-in-human phase 1 trial of TransCon CNP. (2)

Image 1: The TransCon technology. Credits: Ascendis Pharma Company Presentation. 8th May 2018 (1)

Ascendis TransCon technology includes the TransCon CNP that is a long-acting prodrug of a C-type natriuretic peptide (CNP) in development as a therapeutic option for achondroplasia and potentially for other fibroblast growth factor receptor (FGFR)-related skeletal disorders.

Phase 1 is taking place in Australia with healthy volunteers and is a double-blind, randomized and placebo-controlled phase 1 trial will evaluate single ascending doses of TransCon CNP in healthy adult subjects to assess 1. safety, 2. tolerability and 3. pharmacokinetics.

Understanding clinical trials

What is a phase 1?

Phase 1 is the first stage and usually involves small groups of healthy people, or sometimes patients. Phase 1 trials are mainly aimed at finding out how safe a drug is. (3)

Image 2: Medicines development process. Credits: EUPATI (5)

What is a double-blind trial?

In a blind trial, the people taking part are not told which group they are in. This is because if they knew which treatment they
were getting, it might influence how they felt or how they reported their symptoms. Some trials are ‘double blind’, which
means that the people taking part and the doctors treating them do not know who is getting the new treatment. (3)

What is a randomized trial?

When people are put in the trials treatment groups at random, usually by using a computer programme. This is done so that each group has a similar mix of people of different ages, sexes, and states of health.(3)

What is a placebo-controlled trial?

Controlled trials are designed to compare different treatments. Most controlled trials compare a new treatment with the standard
or usual treatment by setting up two groups of people. One group, known as the trial group or intervention group, are given the new
treatment. The other group known as the control group is given the standard treatment and in situations where there is no standard
treatment (as in achondroplasia), the control group may not be given any treatment at all or may be given a ‘placebo’ (a dummy drug). A placebo is designed to look very similar to the treatment being tested. So, in a drug trial the placebo looks exactly like the real drug, but does not do anything. By comparing people’s responses to the placebo and to the treatment being tested, researchers can tell whether the treatment is having any real benefit.(3)

What is pharmacokinetics?

The word is derived from the Greek words pharmakon (drug) and kinetikos (movement), is the study of the disposition of a drug after its delivery to an organism—in short, a study of “what the body does to a drug“. is used to describe the absorption, distribution, metabolism, and excretion of a compound. (4)

Figures 3-5: The TransCon technology. Credits: Ascendis Pharma Company Presentation. 8th May 2018 (1)

Expected timelines for the TransCon CNP clinical trial


Figure 6: adapted from Ascendis Pharma company presentation (1)

Jonathan Leff, M.D., Ascendis Pharma’s Chief Medical Officer. “TransCon CNP has been designed to provide continuous CNP exposure to optimize efficacy without cardiovascular risk in a convenient once-weekly dose. Data from this trial will help validate our target product profile, once again translating our promising preclinical results into clinical data.” (2)

TransCon CNP is the third product candidate in Ascendis Pharma’s rare disease endocrinology pipeline to advance into clinic, developed using its innovative TransCon technology platform. The company anticipates top-line data from the phase 1 trial to be available in the fourth quarter of 2018. (2)



  1. Ascendis Pharma Company Presentation
  2. Ascendis Pharma- Investors and News
  3. NHS”Understanding clinical trial booklet
  4. ScienceDirect “Pharmacokinetics
  5. EUPATI- Medicines development process

May 8, 2018
by inesp.alves

Study on achondroplasia – request for participation in the USA

The Brod Group, a health outcomes research, and consulting firm are currently conducting an international study of pediatric achondroplasia.

Purpose of the study

To get a better understanding of the experiences and daily life of children and adolescents with achondroplasia, as well as the experiences of parents who have children with achondroplasia.

The study findings

Will be used to helping identify important outcomes to consider in future studies of achondroplasia and the results may also be a useful tool to address misconceptions of achondroplasia.

In this document, ACH Study Advertisement you can find additional study details.


This will be an international study and researchers are now looking for participants living in the U.S.A.

  • children with achondroplasia with ages between 9 and 11 years old
  • parents with achondroplasia that also have children with achondroplasia under 18 years of age  (one interview per family)

How will the study be conducted?

  • In a 1-hour telephone interview or a 2-hours focus group (location is to be determined but possibly in New York City)
  • All data will be kept confidential, and no individual will be identified in the study results
  • There is a $125 honorarium for participating in a focus group and a $75 honorarium for participating in a telephone interview

If you are interested in participating, adding value to this research with your personal real-life knowledge on achondroplasia, please contact Jane Beck, Senior Research Associate with The Brod Group:


telephone: (415) 317-3987

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