Therapeutics: rozanolixizumab for primary immune thrombocytopenia

Published: 29-Sep-2020

Primary immune thrombocytopenia (ITP) is a rare acquired autoimmune disorder. Most patients have pathogenic IgG autoantibodies that target platelets and their precursor megakaryocytes

These antibodies remove and destroy both circulating and newly formed platelets, leaving the patient with a propensity for bleeding, spontaneous bruising and extreme fatigue. The standard of care for a newly diagnosed disease is either treatment with corticosteroids or the intravenous (IV) administration of immunoglobulin.

Later, they may be treated with thrombopoietin agonists, immunosuppressants, rituximab or even splenectomy.

An alternative potential treatment is being developed by UCB. Rozanolixizumab is a humanised monoclonal antibody that binds to human antineonatal Fc receptor (FcRn), blocking its interaction with IgG.1 This inhibits IgG recycling and thus induces the removal of the pathogenic IgG autoantibodies.

In a Phase I trial, 49 healthy subjects were randomised to receive 1, 4 or 7 mg/kg or a placebo, either intravenously or via subcutaneous infusion.2

The most frequent treatment-emergent side-effect, headache, was dose-dependent and more prominent in those subjects dosed intravenously. Serious treatment-emergent adverse events occurred in four subjects in the highest IV dose group: headache in three and back pain in the fourth.

Sustained dose-dependent reductions in serum IgG concentrations were seen with the antibody given via either method.

An open label Phase II study has also been reported. In all, 66 patients with persistent or chronic primary ITP were given cumulative doses of 15–21 mg/kg, with multiple doses administered via subcutaneous infusion at weekly intervals (either as five doses of 4 mg/kg, three doses of 7 mg/kg, two doses of 10 mg/kg or either 15 or 20 mg/kg as single doses).3

Subjects were monitored for 8 weeks after treatment ended. In all, 51 subjects reported at least one adverse event, all of which were mild to moderate; the most common were headaches at higher doses, not all of which were deemed to be treatment related.

No discontinuations resulted from adverse events. Rapid, substantial platelet increases were observed, tying in to substantial reductions in IgG. By day 8 in the 15 and 20 mg/kg single dose cohorts, more than half achieved clinically relevant platelet responses, which coincided with the lowest mean IgG levels.

The drug is also being investigated as a potential treatment in other autoimmune diseases driven by pathogenic IgG autoantibodies. These include myasthenia gravis and chronic inflammatory demyelinating polyneuropathy. It has been given orphan drug designation for ITP in both the US and Europe.


  1. B. Smith, et al., MAbs 10, 1111 (2018).
  2. P. Kiessling, et al., Sci. Transl. Med. 9, eaan1208 (2017).
  3. T. Robak, et al., Blood Adv. 4(17), 4136 (2020).

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