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. More from Evaluate Vantage Evaluate HQ 44-(0)20-7377-0800 Evaluate Americas +1-617-573-9450 Evaluate APAC +81-(0)80-1164-4754 © Copyright 2021 Evaluate Ltd. .