Passage Bio Receives European Commission Orphan Designation for PBKR03 for Treatment of Krabbe Disease
Passage Bio announced that the European Commission granted Orphan designation for its investigational gene therapy PBKR03, aimed at treating Krabbe disease, which currently has no approved therapies. The therapy, utilizing a proprietary AAV delivery method, is expected to begin a global Phase 1/2 trial, GALax-C, in the first half of 2021. This designation, along with previous FDA recognitions, emphasizes the urgency for effective treatments for this severe disease. Preclinical data indicate significant potential in improving myelination and clinical outcomes.
- European Commission grants Orphan designation for PBKR03, enhancing market exclusivity prospects.
- PBKR03 has received multiple FDA designations (Fast Track, Orphan Drug, Rare Pediatric Disease) indicating strong regulatory support.
- Preclinical studies show normalization of GALC activity and improved outcomes in a Krabbe canine model.
- No approved disease-modifying treatments currently exist for Krabbe disease, highlighting the high unmet medical need.
- The initiation of the Phase 1/2 GALax-C trial is contingent upon regulatory approval and successful recruitment, which may face delays.
- Krabbe disease, a rare lysosomal storage disorder, has no approved disease-modifying treatment options
- Urgency for effective treatment underscored by European Commission designation for investigational gene therapy PBKR03
- Global Phase 1/2 trial – GALax-C – PBKR03 planned to initiate in first half of 2021
PHILADELPHIA, April 05, 2021 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for rare monogenic central nervous system (CNS) disorders, today announced that the European Commission has granted Orphan designation for PBKR03, an adeno-associated virus (AAV)-delivery gene therapy for the treatment of Krabbe disease (Globoid Cell Leukodystrophy). The designation was based on a positive opinion from the European Medicines Agency Committee for Orphan Medicinal Products. Currently, there are no approved disease-modifying therapies available for Krabbe disease, a rare lysosomal storage disease that most often presents early in a child’s life. The U.S. Food and Drug Administration (FDA) previously granted Fast Track, Orphan Drug and Rare Pediatric Disease designations to PBKR03 for the treatment of Krabbe disease.
“We are planning to initiate in the first half of this year our clinical trial program, GALax-C, to study PBKR03 as a treatment for early infantile Krabbe disease, the most common and severe form of the disorder,” said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. “We're pleased to receive Orphan designation from the European Commission, which — along with multiple FDA designations — reinforces the potential of our approach and the urgent unmet medical need for treatments for infants afflicted with this devastating disease.”
PBKR03 utilizes a next-generation proprietary AAV capsid to deliver, through intra-cisterna magna (ICM) administration, a functional GALC gene to Krabbe patients with mutations in the gene that codes for galactosylceramidase (GAL-C). Low GAL-C activity results in accumulation of psychosine, which is toxic to the myelin-producing oligodendrocytes of the CNS and Schwann cells in the periphery, resulting in damage to both the central and peripheral nervous systems. PBKR03 has the potential to treat both the central nervous system and peripheral nerve manifestations observed in Krabbe disease patients.
Drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions that impact fewer than 5 in 10,000 patients in the European Union qualify for Orphan designation. The designation provides Passage Bio with certain potential benefits, including clinical protocol assistance, reduced regulatory fees, research grants and up to 10 years of market exclusivity following regulatory approval.
Compelling preclinical data support advancement into clinical trials
PBKR03 is supported by extensive preclinical studies, conducted by Passage Bio’s collaborator, the University of Pennsylvania’s Gene Therapy Program (GTP), showing meaningful transduction of both the central and peripheral nervous system in preclinical models, with restoration of myelination in the brain and peripheral nerves. In a naturally occurring Krabbe canine model, a single ICM injection of an AAVhu68 capsid containing the normal canine GALC gene showed normalization of GALC activity, reduction of cerebral spinal fluid psychosine levels, normalization of peripheral nerve conduction velocity, improvement in brain myelination, reduction in brain inflammation and increased survival.
Phase 1/2 GALax-C study anticipated for 1H21
Passage Bio expects to initiate a global Phase1/2 clinical trial, GALax-C, for PBKR03 in the first half of 2021. The trial is designed as a dose-escalation study of a single ICM dose of PBKR03 in pediatric patients with early infantile Krabbe disease. The primary endpoint of the study is safety and tolerability; secondary endpoints include cerebrospinal fluid and serum GALC levels, disease biomarkers, and clinical outcome measures. Initial safety and biomarker data from the trial is anticipated to potentially readout in late 2021 or early 2022, depending on the timing of when the first patient is treated in the study.
More information about the global PBKR03 study, GALax-C, can be found at ClinicalTrials.gov: NCT04771416.
About Krabbe Disease
Krabbe disease is a rare and often life-threatening lysosomal storage disease caused by mutations in the GALC gene, which encodes galactosylceramidase, an enzyme that breaks down galactosylceramide and psychosine. Without adequate levels of galactosylceramidase, psychosine accumulates, causing widespread death of myelin-producing cells and progressive damage to nerves in both the brain and peripheral tissues. The early infantile form of the disease is the most severe and common, typically manifesting before six months of age and accounting for 60 percent to 70 percent of diagnoses. In these patients, the disease course is highly predictable and rapidly progresses to include loss of acquired milestones, staring episodes, apnea, peripheral neuropathy, severe weakness, unresponsiveness to stimuli, seizures, blindness, deafness and eventual death by two years of age. Late infantile patients, defined by onset between seven to 12 months of age, present similar symptoms and have a median survival of approximately five years from onset of symptoms. The estimated worldwide incidence of Krabbe disease is 2.6 in 100,000 births, which is higher than reported due to lack of adequate screening at birth.
About Passage Bio
At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming gene therapies for patients with rare, monogenic CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvania’s Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. This provides our team with enhanced access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at www.passagebio.com.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
For further information, please contact:
Passage Bio Investors:
Stuart Henderson
Passage Bio
267-866-0114
shenderson@passagebio.com
Passage Bio Media:
Gwen Fisher
Passage Bio
215-407-1548
gfisher@passagebio.com
FAQ
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