Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending full, or standard, marketing authorization for Libmeldy (cryopreserved autologous CD34+ cells encoding the arylsulfatase-A, or ARSA, gene), an investigational gene therapy for the treatment of metachromatic leukodystrophy (MLD), characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline.

The CHMP’s positive opinion will now be reviewed by the European Commission (EC), which has the authority to grant marketing authorization for Libmeldy in the European Union (EU). A final decision by the EC for Libmeldy is anticipated before the end of 2020. If approved, Libmeldy would be the first commercial therapy and first gene therapy for eligible patients with early-onset MLD.

MLD is a very rare, severe genetic condition caused by mutations in the ARSA gene which lead to neurological damage and developmental regression. In its most severe and common forms, young children rapidly lose the ability to walk, talk and interact with the world around them. A majority of these patients pass away in childhood, with palliative care often as their only option.

“Today’s positive CHMP opinion for marketing authorization of Libmeldy is a remarkable achievement that we share with the MLD community, as it brings us closer to delivering a one-time, potentially transformative therapy for eligible children suffering from this devastating disease,” said Bobby Gaspar, M.D., Ph.D., chief executive officer, Orchard Therapeutics. “Data from the Libmeldy clinical program have demonstrated the potential for long-term positive effects on cognitive development and maintenance of motor function, translating to individual preservation of motor milestones such as the ability to sit, stand and/or walk without support, as well as attainment of cognitive skills like social interactions and school attendance, at ages at which untreated patients show severe motor and cognitive impairments.”

Libmeldy is designed as a one-time gene therapy, developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy, in which the patient’s own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying genetic condition with a single treatment.

“This is an important milestone toward making the availability of HSC gene therapy a reality for more patients, and it also is extremely rewarding for our multi-disciplinary team at SR-Tiget who has worked relentlessly along this 15-year journey to move the seminal proof of principle studies to the first in-human testing of this therapy,” said SR-Tiget director Luigi Naldini, M.D, Ph.D. “The robust and durable clinical benefits observed in early-onset MLD patients who received HSC gene therapy are compelling, especially when compared to the natural history of the disease. These results also further illustrate our view that the HSC gene therapy approach has the potential to deliver transformative effects in other storage diseases as well, especially when the cells are designed to overexpress the functional enzyme and provide an enhanced supply of it to the affected tissues.”

“As a parent, watching your child start down a seemingly normal developmental path only to suddenly and rapidly lose some or all of his or her abilities is heart-wrenching, and the agony is even more acute knowing no approved therapies currently exist for MLD,” said Georgina Morton, Chair of ArchAngel MLD Trust. “Today’s decision to advance Libmeldy to the final EC approval stage represents a huge step forward for the parents of these young children and for all of us in the MLD community.”

“We are extremely appreciative of the EMA’s expedited and thorough review of Libmeldy’s marketing authorization application, considering the severity of MLD coupled with the limited treatment options available today for young patients,” said Anne Dupraz, chief regulatory officer, Orchard Therapeutics. “The Agency’s collaboration on this assessment is a testament to their broader public health commitment to ensure timely evaluation of new medicines for diseases where a pressing unmet need exists.”

Source: Orchard Therapeutics (Press release)

Een position paper naar ons hart, de nieuwe publicatie van TNO. We zijn steeds beter in staat om patiënten van complexe en gepersonaliseerde medicatie te voorzien. Maar het proces van geneesmiddelontwikkeling is duur, tijdrovend en risicovol. Dat kan sneller en beter: door vol in te zetten op technologische innovaties die het proces versnellen, zoals bijvoorbeeld de Accelerator Mass Spectrometer. TNO pleit voor een gezamenlijke en gecoördineerde aanpak om het proces van medicijnontwikkeling substantieel te verbeteren. We moeten op zoek naar de win-win voor alle betrokken partijen in het systeem, zodat we oplossingen realiseren waarbij gezondheidswinst, innovatie én betaalbaarheid hand in hand gaan, een kolfje naar HollandBIO’s hand.

Lees het hele position paper hier.