Pharming Turns to Gene Therapy for Next-Gen HAE Therapy

July 01, 2021 Pharming turns to gene therapy for next-gen HAE therapy

Lisa Urquhart

Hereditary angioedema (HAE) has gone from an intractable, life-threatening, rare disease to a field with eight marketed drugs in just 13 years. If Pharming has its way one of the next additions could be a gene therapy. The Dutch group has inked a $17.5m up-front deal with Orchard Therapeutics for worldwide rights to OTL-105. OTL- 105 works by inserting one or more functional copies of the SERPING1 gene into patients' own hematopoietic stem cells ex vivo, enabling production of the C1-INH protein HAE patients lack. Pharming could well steal a march on market leader Takeda by investing in gene therapy now; the Japanese giant, whose Takhzyro is forecast to hit blockbuster status this year, does not appear to have a stake in any such technology in HAE. Nearer term-innovation in HAE includes Kalvista and Pharvaris's oral projects in both the acute and prophylactic space. Several groups are looking at longer-acting mechanisms, including CSL with its once monthly MAb, while in vivo gene editing and RNAi projects are in early stages elsewhere. Should these approaches succeed a less convenient gene therapy could well prove useful only for the most severe cases, but with much work still to be done that remains a debate for the future.

Selected long-acting and cell and gene therapy HAE projects

Company Description

Phase III

Garadacimab CSL Once-monthly MAb for prophylaxis

Phase II

IONIS-PKK-LRx Ionis Pharmaceuticals Once-monthly antisense for prophylaxis

Pre-clinical

ALN-F12 Alnylam Pharmaceuticals RNAi targeting coagulation factor XII

BMN 331 BioMarin Pharmaceutical AAV5-based gene therapy

NTLA-2002 Intellia Therapeutics Prekallikrein (PKK) antisense

Un-named Regenxbio AAV gene therapy

Un-named Orchard/Pharming Autologous hematopoietic stem cell gene therapy

Source: Evaluate Pharma.