Pharming turns to gene therapy for next-gen HAE therapy

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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. 

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