Delivering aGal (RPV-001) to the right place via the native receptor

Eleva has published promising preclinical and clinical Phase 1b data for its recombinant version of alpha-galactosidase aGal (RPV-001), a key target in enzyme replacement therapy in Fabry disease.

The recombinant aGal (RPV-001) program is a prime example for the positive impact of our proprietary expression system on key product capabilities otherwise unattainable with conventional production cell lines.

In Fabry disease, patients are at risk of acute or chronic pain, significant damage to the heart, kidney, and blood vessels that can be fatal. The condition is caused by a lack or an impaired function of the enzyme a-galactosidase (aGal), which leads to an abundance of sphingolipids accumulating in cells, more precisely the cell’s storage compartment called lysosomes, and tissues. Fabry disease is a rare disease, but its prevalence is considered to be strongly underestimated and improvements in diagnostics may lead to more patients receiving a correct diagnosis earlier.

Currently available treatments for Fabry disease, a well-established therapeutic segment for enzyme replacement strategies, generate sales well in excess of US-$ 1 billion per year. Being a chronic condition, the unmet medical need increasingly shifts towards improved safety and tolerability. Products with improved pharmacodynamics unlocking more convenient dosing schedules, ways of administration and ultimately achieving better cost effectiveness have significant market potential.

Dr. Henrik Luessen,
Chief Business Officer

“Our glyco-optimized aGal (RPV-001) for the treatment of Fabry disease could enable extended treatment intervals with less side effects.”

Eleva has generated preclinical and clinical results from a Phase 1b trial for its recombinant version of alpha-galactosidase aGal (RPV-001) indicating a lasting therapeutic effect measured by a reduction in sphingolipid levels over the course of 28 days following a single injection. We were also able to show that cell uptake of aGal (RPV-001) is faster compared to mammalian cell-based products, and is more directed to the relevant organs, namely the kidneys. The glycosylation pattern our moss-based expression process provides likely drives uptake of aGal (RPV-001) via the mannose receptor.

Eleva is currently evaluating strategic alliances to accelerate the development of the aGal (RPV-001) program towards market approval.

Publications
  • Mannose receptor-mediated delivery of moss-made α-galactosidase A efficiently corrects enzyme deficiency in Fabry mice

    Shen JS, Busch A, Day TS, Meng XL, Yu CI, Dabrowska-Schlepp P, Fode B, Niederkrüger H, Forni S, Chen S, Schiffmann R, Frischmuth T, Schaaf A

  • Pharmacokinetics, pharmacodynamics, and safety of moss‐aGalactosidase A in patients with Fabry disease

    Hennermann JB, Arash-Kaps L, Fekete G, Schaaf A, Busch A, Frischmuth T

  • Comparison of efficacy between subcutaneous and intravenous application of moss-aGal in the mouse model of Fabry disease

    Dabrowska-Schlepp P, Busch A, Shen JS, Cheong RY, Madsen LB, Mascher D, Schiffmann R, Schaaf A

  • Jun 13, 2024

    ...will focus on diagnostics and the disease spectrum of C3 Glomerulopathy, zooming in on histological spectrum.

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