- Forge fulfills European Medicines Agency’s (EMA) GMP manufacturing standards as determined by a QP audit and declaration to support clients intending to export gene therapy products for clinical programs in Europe
COLUMBUS, Ohio – April 24, 2023 – Forge Biologics, a leading manufacturer of genetic medicines, today announced that its manufacturing facility has successfully completed the audits necessary and received QP declaration for its gene therapy manufacturing facility, thereby fulfilling the European Union Good Manufacturing Practices (EU GMP) requirement to manufacture investigational medicinal products and allowing Forge to support European-based clinical trials.
“QP declaration enhances Forge’s position as a leading global AAV manufacturer able to support clients with the production of high quality therapeutic products destined for European distribution, and helping them to reach patients needing treatments as quickly as possible,” said Christopher Shilling, Senior Vice President of Regulatory Affairs and Quality at Forge.
A European QP has completed a comprehensive and in-depth audit focused on the quality management systems (QMS) and platform AAV manufacturing process at Forge’s manufacturing facility in Columbus, Ohio, and determined that its facilities, raw materials, suppliers, procedures, and quality systems meet EU GMP requirements. In the EU, a QP is responsible for certifying that each batch of a medicinal product meets all required provisions when released from a manufacturing facility within the EU or imported into the EU.
Having fulfilled Europe’s GMP requirements, Forge has reached another key regulatory milestone, expanding its CDMO services to support clients in the United States and Europe. Forge clients can rely on the Company’s QP audit as one less hurdle they need to overcome when their AAV gene therapy products are being manufactured for clinical trials and on the path to commercialization in European countries. The QP declaration was received in support of Forge’s internal FBX-101 clinical gene therapy program for the treatment of patients with Krabbe disease.
“The declaration is a significant milestone that demonstrates Forge’s capability to pass the EU QP audit and obtain QP declaration, which will enable us to manufacture products for gene therapy programs to treat patients in the U.S. and Europe,” said Meghan Leonard, Vice President of Quality Management at Forge.
The QP declaration adds to Forge’s capabilities and makes the Company among one of the few U.S. AAV CDMO’s able to support clients intending to export gene therapy products for clinical programs in Europe.
About Forge Biologics
Forge Biologics is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company. Forge’s mission is to enable access to life-changing gene therapies and help bring them from idea to reality. Forge’s 200,000 square foot facility, the Hearth, utilizes 20 cGMP suites in Columbus, Ohio, to serve as its headquarters. The Hearth is a custom-designed cGMP facility dedicated to AAV manufacturing and hosts scalable, end-to-end manufacturing services. Offerings include process and analytical development, plasmid DNA manufacturing, viral vector manufacturing, final fill, as well as regulatory consulting support to accelerate gene therapy programs from preclinical through clinical and commercial stage manufacturing. By taking a patients-first approach, Forge aims to accelerate the timelines of these transformative medicines for those who need them the most. To learn more, visit www.forgebiologics.com.
Media Inquiries
Marina Corleto – Forge Biologics
Associate Director, Marketing and Communications
media@forgebiologics.com
- FBX-101 is granted priority medicines (PRIME) designation by the European Medicines Agency (EMA) after review of Phase 1/2 RESKUE clinical trial safety and efficacy data
- PRIME designation is granted to drug candidates that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options
COLUMBUS, Ohio – January 17, 2023 – Forge Biologics, a gene therapy-focused contract development and manufacturing organization, today announced that the European Medicines Agency (EMA) has granted priority medicines (PRIME) designation to FBX-101, Forge’s lead adeno-associated virus (AAV) drug candidate and novel gene therapy for treating patients with Krabbe disease.
PRIME is a regulatory designation by the EMA that provides early and proactive support to developers of promising medicines, to advance and speed up their development and usher them to reach patients faster. The goal is to help patients benefit as early as possible from innovative new therapies that have demonstrated the potential to significantly address and treat patients that have an unmet medical need.
“We are grateful to the EMA for recognizing FBX-101 as a potentially transformative medicine for patients living with this life-threatening and devastating disease,” said Christopher Shilling, Senior Vice President of Regulatory Affairs and Quality at Forge. “Through the enhanced interactions with the EMA granted by the PRIME designation, we will advance and expedite the development of FBX-101 as the leading worldwide gene therapy for patients with Krabbe disease.”
The designation follows positive safety and efficacy data from the ongoing Phase 1/2 RESKUE trial. This positive clinical data was presented by Maria Escolar, M.D., Forge’s Chief Medical Officer at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in August 2022, and updated in October at the 29th Congress of European Society of Gene & Cell Therapy (ESGCT). The results demonstrated that systemically delivered FBX-101 administered after hematopoetic stem cell transplant (HSCT) is safe and well-tolerated in Krabbe patients. Patients in the low dose cohort demonstrated restoration of GALC enzyme activity, reduced psychosine, showed encouraging signs of normal myelination of brain white matter, and improved motor development as compared to untreated Krabbe patients or patients treated with HSCT alone.
Clinical data support preclinical observations that this gene therapy approach after HSCT infusion may lessen many of the immune challenges previously observed with systemic AAV gene delivery and may create a safer environment for gene replacement. Findings also support this novel approach for extending the delivery of gene replacement strategies to target metabolic diseases amenable to HSCT.
About Krabbe Disease
Krabbe disease is a rare neurodegenerative disease affecting about 1-2.5 in 100,000 people in the U.S. Krabbe disease is caused by autosomal recessive mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine, associated with myelination of the nervous system. Without functional GALC, psychosine accumulates to toxic levels in cells, specifically in cells insulating the nerves in the brain and peripheral nervous system, causing rapid demyelination. Krabbe disease initially manifests as irritability, developmental delay, and progressive muscle weakness; symptoms rapidly advance to difficulty swallowing, breathing, worsening developmental delay, and vision and hearing loss. Infantile Krabbe disease (0 –12 months of age at onset) usually leads to death in untreated patients by 2 years of age. Late Infantile patients (12-36 months of age at onset) usually die by the age of six. The current standard of care, hematopoietic stem cell transplantation (HSCT), has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes when performed prior to symptom onset. However, HSCT does not correct the peripheral neuropathy that is progressive as the patient grows, leading to loss of gross motor skills and eventually death. Early diagnosis is key for treating Krabbe patients before significant neurological damage has occurred. Currently, 10 states in the USA are conducting newborn screening for Krabbe disease. Infants who screen positive, meaning insufficient GALC activity is detected, undergo psychosine and mutation analysis to confirm the diagnosis and predict disease onset.
About FBX-101
FBX-101 was developed to treat children with Krabbe disease. FBX-101 is an adeno-associated viral serotype rh10 (AAVrh10) gene therapy that is delivered intravenously after HSCT infusion. The vector delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral neuropathy associated with Krabbe, improve gross motor outcomes, and significantly prolong lifespan in animal models. This approach has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies and extend the duration of gene transfer.
About the RESKUE Trial
RESKUE a Phase 1/2 clinical trial to investigate the safety and efficacy of FBX-101 in patients with Infantile Krabbe disease. It is a nonblinded, non-randomized dose escalation study of intravenous AAVrh10 after HSCT infusion, in which subjects receive standard of care hematopoietic cell transplantation for Krabbe Disease, followed by a single infusion of an adeno-associated virus gene therapy product. Extensive natural history subjects will be used to compare as control group. More information on the RESKUE trial can be found online at https://www.clinicaltrials.gov/ct2/show/NCT04693598.
About Forge Biologics
Forge Biologics is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company. Forge’s mission is to enable access to life changing gene therapies and help bring them from idea to reality. Forge’s 200,000 square foot facility utilizes 20 cGMP suites in Columbus, Ohio, the Hearth, to serve as its headquarters. The Hearth is a custom-designed cGMP facility dedicated to AAV manufacturing and hosts scalable, end-to-end manufacturing services. Offerings include process and analytical development, plasmid DNA manufacturing, viral vector manufacturing, final fill, as well as regulatory consulting support to accelerate gene therapy programs from preclinical through clinical and commercial stage manufacturing. By taking a patients-first approach, Forge aims to accelerate the timelines of these transformative medicines for those who need them the most. To learn more, visit www.forgebiologics.com.
Media Inquiries
Marina Corleto – Forge Biologics
Associate Director, Marketing and Communications
media@forgebiologics.com
Families and Clinician Inquiries
Maria Escolar, M.D. – Forge Biologics
Chief Medical Officer
medicalaffairs@forgebiologics.com
Business Development
Magdalena Tyrpien – Forge Biologics
Senior Vice President, Head of Business Development
BD@forgebiologics.com
- FBX-101 Received Orphan Designation from the EMA for Gene Therapy to Treat Patients with Krabbe Disease
- Company Also Received Positive Feedback from FDA on AAV cGMP Manufacturing Production Processes Including Use of Proprietary Plasmids and HEK293 Master Cell Bank
- Forge’s Proprietary Ignition™ HEK293 Suspension Cell Line and pEMBR™ Helper Plasmid Deemed Suitable for cGMP AAV Manufacturing
COLUMBUS, Ohio – September 20, 2021 – Forge Biologics, a gene therapy-focused contract development and manufacturing organization, today announced that it has received additional designations and regulatory feedback from the European Medicines Agency (EMA) and the U.S. Food & Drug Administration (FDA), advancing the manufacturing capabilities for its own and clients’ AAV gene therapies.
The EMA has granted orphan designation for the company’s clinical-stage gene therapy FBX-101 for the treatment of patients with Krabbe disease. FBX-101 is a first-in-human potential treatment utilizing a systemically administered adeno-associated virus (AAV) to deliver the correct version of the faulty gene responsible for an abnormality in patients with Krabbe disease, a rare and fatal genetic disorder. FBX-101 previously received Orphan Drug and Rare Pediatric Disease Designations from the FDA earlier this year.
“FBX-101 is the culmination of over 20 years of scientific research to understand the challenges faced by patients with progressive disease after hematopoietic stem cell transplantation, the current standard of care,” said Maria Escolar, M.D., Forge’s Chief Medical Officer. “We are currently recruiting patients for our RESKUE clinical trial to administer FBX-101and we are pleased by the EMA’s designation so that patients in Europe may also have access to this potentially transformative therapeutic approach.”
The company also announced that the FDA has provided positive feedback on Forge’s AAV manufacturing processes, including use of its exclusive production plasmids and master cell bank for cGMP manufacturing of gene therapies.
Forge presented information to the FDA on its proprietary HEK293 suspension cell line, Ignition™ Cells, and adenovirus helper plasmid, pEMBR™, and received FDA alignment that these technologies are suitable for cGMP manufacturing of clinical drug products.
“We are excited that the tools we have developed at Forge will help accelerate and scale cGMP production of AAV gene therapies for patients. We are thankful to have a positive dialogue with the EMA and for gaining alignment with the FDA on the suitability of our key production materials for our own and our clients’ use,” said Christopher Shilling, Vice President of Regulatory Affairs and Quality. “These new technologies can help mitigate current safety concerns surrounding critical raw materials used in AAV scale-up and production processes for programs moving from research to clinical stage.”
Forge offers “concept to clinic” AAV manufacturing and development services to accelerate gene therapy programs from preclinical stage through clinical with technology platforms enabling fully traceable cell line history for potential commercialization.
About Krabbe Disease
Krabbe disease is a rare, pediatric leukodystrophy affecting about 1-2.5 in 100,000 people in the U.S. and is inherited in an autosomal recessive manner. Krabbe disease is caused by loss-of-function mutations in the galactosylceramidase (GALC) gene, a lysosomal enzyme responsible for the breakdown of certain types of lipids such as psychosine. Without functional GALC, psychosine accumulates to toxic levels in cells. The psychosine toxicity is most severe in the myelin cells surrounding the nerves in the brain and in the peripheral nervous system, eventually leading to the death of these cells. The disease initially manifests as physical delays in development, muscle weakness and irritability and advances rapidly to difficulty swallowing, breathing and cognitive problems, and vision and hearing loss. Early onset or “Infantile” Krabbe disease cases usually results in death of patients by the age of two years, while later onset or “Late Infantile” patients usually die by the age of six. There is currently no approved treatment for Krabbe disease.
About FBX-101
Forge developed FBX-101 to treat patients with Infantile Krabbe disease. FBX-101 is an adeno-associated viral (AAV) gene therapy that is typically delivered after a hematopoietic stem cell transplant. FBX-101 delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral neuropathy and correct the behavioral impairments associated with Krabbe disease in animal models, as well as to drastically improve lifespan in animal models of the disease. This approach has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies.
About Orphan Designation
EMA orphan designation is designed to encourage the development of new treatments for life-threatening or chronically debilitating conditions that are rare (affecting not more than five in 10,000 people in the European Union). Medicines like FBX-101 that meet the EMA’s orphan designation criteria qualify for several incentives, including extended market exclusivity, protocol assistance, and potentially reduced fees for regulatory activities. The orphan designation is issued by the EMA Committee for Orphan Medicinal Products (COMP) for use in the European Union.
About Forge Biologics
Forge Biologics is a hybrid gene therapy contract manufacturing and therapeutics development company. Forge’s mission is to enable access to life changing gene therapies and help bring them from idea into reality. Forge has a 175,000 square foot facility in Columbus, Ohio, The Hearth, to serve as its headquarters. The Hearth is a custom-designed cGMP facility dedicated to AAV vector manufacturing and will host end-to-end manufacturing services to accelerate gene therapy programs from preclinical through clinical and commercial stage manufacturing. By taking a patients-first approach, Forge aims to accelerate the timelines of these transformative medicines for those who need them the most. For more information, please visit https://live.forgeabps.com.
Media Inquiries
Marina Corleto – Forge Biologics
Senior Manager, Marketing and Communications
media@forgebiologics.com
Families and Clinician Inquiries
Dr. Maria Escolar – Forge Biologics
Chief Medical Officer
medicalaffairs@forgebiologics.com
Business Development
Magdalena Tyrpien – Forge Biologics
Vice President and Head, Business Development
BD@forgebiologics.com
Client Development
John Maslowski – Forge Biologics
Chief Commercial Officer
CD@forgebiologics.com
Investor Relations
Christina Perry, MSA, CPA – Forge Biologics
Vice President, Finance and Investor Relations
Investors@forgebiologics.com