Japan’s Otsuka Pharmaceutical has signed a license agreement with US-based biotechnology company Ionis Pharmaceuticals for the latter’s hereditary angioedema (HAE) treatment, donidalorsen.

Donidalorsen is a ligand-conjugated antisense (LICA) drug designed to target the prekallikrein (PKK) pathway, which plays a key role in activating inflammatory mediators related to HAE.

Under the terms of the license agreement, Otsuka will acquire exclusive rights to market donidalorsen in Europe in exchange for an upfront payment of $65m.

Ionis will also receive milestone payments contingent on achieving regulatory and sales targets and is eligible to receive royalties on product sales.

Otsuka will be responsible for regulatory submissions and exclusive commercialisation of donidalorsen in Europe.

Ionis CEO Brett Monia said: “We are excited to collaborate with Otsuka given their proven results in bringing rare disease medicines to patients in Europe.

“This agreement is aligned with our strategy to initially focus our commercialisation efforts on the US market.

“We are encouraged by the strong product profile of donidalorsen to date and look forward to reporting pivotal topline Phase 3 donidalorsen results in HAE in the first half of next year.”

Recently, Ionis announced two-year results from the Phase 2 open-label extension (OLE) study and secured Orphan Drug Designation for donidalorsen in the US.

In the Phase 2 study, treatment with donidalorsen showed a 96% overall sustained mean reduction from baseline in HAE attack rates.

The study also showed efficacy in reducing HAE attacks and a favourable safety and tolerability profile for the drug.

Ionis is currently conducting a Phase 3 study, with plans to announce results in the first half of 2024.

Injection site (IS) discolouration and IS reaction are the only adverse events (TEAEs), with no serious adverse events reported in the OLE study, and no TEAEs led to study discontinuation.

Furthermore, Ionis plans to independently commercialise donidalorsen in the US, if approved.

Otsuka Pharmaceutical president and representative director Makoto Inoue said: “Otsuka has developed drugs in Europe for rare diseases such as autosomal dominant polycystic kidney disease (ADPKD).

“Through this collaboration with Ionis, a leader in RNA-targeted therapy, if regulatory approval is received, we look forward to bringing donidalorsen to patients in Europe to address the unmet medical needs of patients with HAE.”

Earlier this year, Otsuka teamed up with US-based Shape Therapeutics to develop intravitreally delivered adeno-associated virus (AAV) therapeutics for ocular diseases.