The European Commission (EC) has granted the Orphan designation to Passage Bio for their Krabbe disease treatment, PBKR03. This adds another designation to the medication’s list, as it has already received the Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the United States Food and Drug Administration (FDA). Krabbe disease patients face a severe unmet medical need, and these designations are a step in the right direction.

About Krabbe Disease

Krabbe disease, also called globoid cell leukodystrophy, is a rare disorder that causes the destruction of myelin in the brain and nervous system. It can range in severity between affected individuals, but it is typically fatal by age two. Symptoms include fever, difficulties feeding, vomiting, loss of head control, developmental delays, irritability, unexplained crying, muscle spasms, and declines in alertness. These effects are all the result of a mutated gene that is inherited in an autosomal recessive pattern. This gene is responsible for an enzyme called galactocerebrosidase (GALC), and when there is not enough of it, it allows fats to accumulate. This buildup then results in the destruction of myelin. Unfortunately, there is no cure for this condition. Treatment is symptomatic.

About Orphan Designation

In order to qualify for the Orphan designation, a medication or biologic must be intended for the treatment, prevention, or diagnosis of a rare disease that affects less than five of every 10,000 people in the EU. Companies who receive this designation receive benefits like lower fees, up to a decade of market exclusivity, research grants, and clinical protocol assistance.

About PBKR03

PBKR03 is an adeno-associated virus (AAV)-delivery gene therapy that delivers a working version of the GALC gene through intra-cisterna magna (ICM) administration. It is intended to treat both the peripheral nerve and central nervous system manifestations of the disease.

PBKR03 Research

The University of Pennsylvania’s Gene Therapy Program has conducted preclinical trials that produced evidence supportive of progression into human trials. Data demonstrated that symptoms of the central and peripheral nervous systems were reduced; remyelination was seen in the brain and peripheral nerves. A canine model treated with a single dose saw:

• Normalized GALC activity
• Reduced inflammation of the brain
• Normalized peripheral nerve conduction velocity
• Remyelination in the brain
• Reduced cerebral spinal fluid psychosine levels
• Increased survival

Looking Forward

The next step for PBKR03 is a Phase 1/2 trial titled GALax-C. Passage Bio expects to initiate the trial in the first half of this year, and it is designed as a dose-escalation study of one dose of PBKR03 in patients with early infantile Krabbe disease under age 18.

Researchers will be evaluating the treatment’s safety and tolerability as the study’s primary endpoint. Cerebrospinal fluid and serum GALC levels, clinical outcome measures, and biomarkers will serve as secondary endpoints. Initial data is expected by the end of 2021 or the beginning of 2022.

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