Bridgebio pharma announces positive phase 2 data for limb-girdle muscular dystrophy type 2i (lgmd2i) Read more
Pre-clinical Phase
Laboratory and animal testing to answer basic questions of safety and demonstrate potential effectiveness.
targeting Limb-Girdle Muscular Dystrophy Type 2I at its source.
ML Bio Solutions aims to develop the first-ever safe and effective substrate supplementation therapy for Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I), a rare genetic disease causing muscle degeneration and leading to immobility, respiratory impairment and cardiac failure.
What is Limb-Girdle Muscular Dystrophy Type 2I (LGMD2i)?
LGMD2I (also called “LGMD R9 FKRP-related” in the new proposed nomenclature) is an inherited disease caused by a mutation in the FKRP gene. Although the disease is primarily diagnosed in adolescents 10 – 20 years old, children have been diagnosed as young as two years old. Patients with LGMD2I experience progressive muscle weakness, that affects skeletal, respiratory and cardiac muscles. While every patient experience is different, muscle weakness typically begins in the shoulder and hip areas, resulting in the need for assistance with mobility.
The FKRP gene is involved in helping muscles build a glycoprotein called alpha dystroglycan. Alpha dystroglycan acts as a “shock absorber,” and when it doesn’t work correctly, as occurs in patients with LGMD2I, the shock absorbing function is significantly reduced. This leads to damage to muscle tissue and replacement, over time, with scar-like, fibrotic tissue. As fibrotic tissue overtakes healthy muscle tissue, muscle strength and function declines, and patients lose the ability to perform routine daily activities unassisted – such as walking or standing up.
Over time, muscle degeneration can become so excessive as to result in respiratory and cardiovascular issues, leading to respiratory or cardiac arrest and death. Currently, people with LGMD2I have no treatment options beyond steroid injections and other symptom and pain management techniques. The LGMD2I community has made exceptional strides to spread awareness of the unmet medical need, as well as to create a network connecting patients with physician experts in the field of neuromuscular diseases.
For additional information and resources, several advocacy organizations are working to help people diagnosed with LGMD2I as well as their families. Click here to view these organizations.
Affected Muscles
1
2
3
1
skeletal muscle
2
respiratory muscle
3
cardiac muscle
Drug Development Pathway
Most new treatments pass through 3 phases of clinical trials before they are approved to establish safety and how well they work. The purpose of these clinical trials is to determine whether there is benefit to the patient from receiving the drug. Often, a 4th phase is used to monitor the treatment over time after approval.
Patient engagement over the course of drug development is vital to gain an understanding of the impact of the disease on the patient community.
As important stakeholders in the drug development process, patients, family members and caregivers can provide unique and valuable perspectives that can inform evaluation of a medicine’s benefits and risks and provide the context for FDA’s decision making.
BBP-418 Development
Science
Alpha Dystroglycan is an essential component of a muscular shock absorber that contributes to structural integrity of muscle cells during the beating of our hearts, the expansion and contraction of our chests during breathing, and the movement of our arm and leg muscles. Glycoproteins like alpha dystroglycan join in an array with muscles made possible by enzymes – including FKRP – that add sugars to alpha dystroglycan in an assembly line-like fashion. Mutations in the gene that codes for FKRP cause the genetic disease limb girdle muscular dystrophy type 2I (LGMD2I), where alpha dystroglycan can’t work effectively as a shock absorber and, as a result, muscles sustain damage over time.
BBP-418 is a sugar that the body produces naturally and supplements the substrate that is incorporated into alpha dystroglycan to allow it to function normally. Published studies have validated the role of BBP-418 as a limiting constituent to alpha dystroglycan’s shock absorber function. ML Bio Solutions is investigating BBP-418 as a potential therapy for treating patients affected by mutations to FKRP.
Different forms of LGMD2I exist, depending on the severity of the specific gene mutation. In the United States, LGMD2I has a prevalence of more than one in every 250,000 persons. There is currently no effective or disease-modifying treatment available to patients.
References:
Cataldi, M.P., Lu, P., Blaeser, A. et al. Ribitol restores functionally glycosylated α-dystroglycan and improves muscle function in dystrophic FKRP-mutant mice. Nat Commun 9, 3448 (2018). https://doi.org/10.1038/s41467-018-05990-z; https://www.nature.com/articles/s41467-018-05990-z
Motoi Kanagawa, Kazuhiro Kobayashi, Michiko Tajiri, Hiroshi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Keiko Akasaka-Manya, Jun-ichi Furukawa, Mamoru Mizuno, Hiroko Kawakami, Yasuro Shinohara, Yoshinao Wada, Tamao Endo, Tatsushi Toda. Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy, Cell Reports, Volume 14, Issue 9, 2016, Pages 2209-2223. https://www.sciencedirect.com/science/article/pii/S2211124716301036
Gerin, I., Ury, B., Breloy, I. et al. ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto α-dystroglycan. Nat Commun 7, 11534 (2016). https://doi.org/10.1038/ncomms11534; https://www.nature.com/articles/ncomms11534
Theoretical Mechanism of Action BBP-418
Healthy Muscle Tissue
LGMD2i
ML Bio Solutions
LGMD2I Lead-in Study
A Natural History Study (also known as Lead-in Study) in LGMD2I collects information about what endpoints and metrics most consistently reflect meaningful clinical outcomes for patients. Studies like this are often integral in developing effective treatments for disease – particularly rare diseases like LGMD2I. This study is fully enrolled in the United States.
We Put Patients First
- At ML Bio Solutions we work to establish and build relationships with the LGMD2I community.
- We respect the independence of patient organizations and the unique perspective of every advocate, patient, and family member.
- We actively seek to include the perspective of patients, families, and advocates in the drug development process by listening and learning from them.
- We are seeking to develop a drug that is safe and effective for patients.
ML Bio Solutions Recognizes LGMD Awareness Day
In honor of LGMD Awareness Day, we introduce you to Sammy, a teenager living with limb-girdle muscular dystrophy 2i (LGMD2i). We are grateful to Sammy and her family for sharing their story.
Patient Stories
Read about the journeys of people living with LGMD2I.
Meet Cyndy
A busy wife, mother, attorney and dog-lover, Cyndy has been living with LGMD2I for over 25 years… read more.
Meet Julie
Julie is a 39-year-old mother of three, a graduate student in counseling psychology and… read more.
Meet Seamus
13-year-old Seamus is a 7th grader currently living with his family in Coatesville, Pennsylvania… read more.
Patient Resources
ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world.
This video is courtesy of Courageous Parents Network. Visit courageousparentsnetwork.org for more parent and provider content on evaluating the clinical trial option.
Genetic Testing 101: An informational video about genetic testing.
What is genetic testing? Genetic testing confirms the specific gene mutagions implicated in a genetic condition. Confirmation of diagnosis is necessary for participation in clinical trials and to be eligible for treatments as they are developed.
It is important to obtain a genetically-confirmed diagnosis as it can open doors to participating in clinical trials and other research as well as determine treatment options for your particular condition. Genetic testing can help predict how a disease might progress and give you and your treatment team vital information for targeting therapies and management strategies.
Please discuss genetic testing with your health care provider to determine the best route for you.
Free Genetic Testing
Here are some resources for free genetic testing:
- The Lantern Project: Sanofi Genzyme is partnering with PerkinElmer Genomics to offer a complimentary genetic testing program called The Lantern Project. It offers free diagnostic testing for several disorders, including LGMD.
- Detect Muscular Dystrophy is a no-charge genetic testing and counseling program for individuals suspected of having muscular dystrophy offered in partnership with INVITAE. This program is for individuals in the U.S. and Canada who meet eligibility guidelines. You can find info on it at this link and patients can share it with their clinical team to get started. The kits have to be ordered by the physician and the order has to be filled out a certain way but those instructions are on the webpage. You can learn more about Detect Muscular Dystrophy by visiting Detect Muscular Dystrophy or by contacting INVITAE’s Client Services at 800-436-3037.
ML Bio Solutions has no role, responsibility, endorsement, or relationship with any testing program, and is providing this information purely for informational purposes.
Currently, ML Bio Solutions does not offer an expanded access program and is unable to make its investigational products available to patients outside of clinical trials at this time.
If you are a healthcare provider and have questions about ML Bio’s expanded access policy please contact info@mlbiosolutions.com. You should expect a response within 5 business days. If you would like to learn more about the Expanded Access process, the FDA provides information here.
To learn about potential eligibility for ML Bio investigational products within clinical trials, please reference this link: www.clinicaltrials.gov
Patient Advocacy Organizations
Several advocacy organizations are working to help people who are living with neuromuscular diseases and their families. Below are links to these organizations. Click on the logo to be directed to their web sites where you can find resources, information, videos and opportunities to connect with others.
Management
Christine Siu
Chief Executive Officer
Douglas M. Sproule, M.D., MSc
Chief Medical Officer
Anna Devries, JD, MHA
Vice President, Legal and Operations
Anna Wade
Chief Operating Officer
Uma Sinha, Ph.D.
Chief Scientific Officer
Tricia Blankenbiller
Senior Vice President, Clinical Operations
Jennifer Pavillard
Vice President, Head of Regulatory Affairs
Cybele Gouverneur
Senior Manager, Patient Advocacy
Board of Directors
Luther Lockwood
Board Chair and President of ML Bio Solutions
Christine Siu
Chief Executive Officer in Residence, BridgeBio
Leonard Post, Ph.D.
Chief Scientific Officer, Vivace Therapeutics
Rasu Shrestha, M.D.
Executive Vice President and Chief Strategy Officer, Atrium Health
Thomas Trimarchi, Ph.D.
Chief Product Officer, BridgeBio
Adora Ndu, Pharm.D., J.D.
Chief Regulatory and Interim Legal Officer, BridgeBio
Jonathan C. Fox, M.D., Ph.D., FACC
President and Chief Medical Officer, Eidos Therapeutics
Scientific Founder
Qi Long Lu, M.D., Ph.D.
ML Bio Solutions IS A MEMBER OF THE BRIDGEBIO FAMILY
BridgeBio is a team of experienced drug discoverers, developers and innovators working to create life-altering medicines that target well-characterized genetic diseases at their source. BridgeBio was founded in 2015 to identify and advance transformative medicines to treat patients who suffer from Mendelian diseases, which are diseases that arise from defects in a single gene, and cancers with clear genetic drivers. BridgeBio’s pipeline of several dozen development programs includes product candidates ranging from early discovery to late-stage development.
News
Press Releases
- bridgebio pharma announces positive phase 2 data for limb-girdle muscular dystrophy type 2i (lgmd2i) 03.14.2022
- BridgeBio Pharma, Inc. to Host Investor Call to Discuss Phase 2 Data for Limb-girdle Muscular Dystrophy Type 2i (LGMD2i)
03.11.2022 - BridgeBio Pharma Receives FDA Fast Track Designation for Investigational Therapy for the Treatment of Limb-girdle Muscular Dystrophy Type 2i (LGMD2i)
09.15.2021 - BridgeBio Pharma And Affiliate ML Bio Solutions Announce Dosing Of First Patient In Phase 2 Trial Of BBP-418 In Limb Girdle Muscular Dystrophy Type 2i (LGMD2i)
02.19.2021 - BridgeBio Pharma’s ML Bio Solutions Announces Dosing of First Subject in Phase 1 Clinical Trial of BBP-418 For Limb Girdle Muscular Dystrophy Type 2I (LGMD2I)
06.11.2020 - BridgeBio Pharma expands its research into neuromuscular disease to include Limb-Girdle Muscular Dystrophy Type 2 (LGMD2I) with new subsidiary ML Bio Solutions
09.05.2019
