Pharming turns to gene therapy for next-gen HAE therapy

 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.  https://www.evaluate.com/vantage/articles/news/snippets/pharming-turns-gene-therapy-next-gen-hae-therapy