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EP-3958897-B1 - MIRIKIZUMAB FOR USE IN A METHOD OF TREATING CROHN'S DISEASE

EP3958897B1EP 3958897 B1EP3958897 B1EP 3958897B1EP-3958897-B1

Inventors

  • FRIEDRICH, Stuart William
  • POLLACK, Paul Frederick
  • TUTTLE, Jay Lawrence

Dates

Publication Date
20260506
Application Date
20200415

Claims (5)

  1. Mirikizumab for use in the treatment of CD, said treatment comprising: a) administering three induction doses of mirikizumab to the patient by intravenous injection, wherein each induction dose comprises about 900 mg of mirikizumab and wherein the three induction doses of mirikizumab are administered at about 4 week intervals; and b) administering maintenance dose(s) of mirikizumab to the patient by subcutaneous injection at about 4 week or about 8 week intervals, wherein the first maintenance dose is administered about 4 weeks or about 8 weeks after the last induction dose is administered and wherein each maintenance dose comprises 200 mg or 300 mg of mirikizumab, wherein the CD is moderate to severe CD.
  2. Mirikizumab for use in the treatment of CD according to claim 1, wherein the patient is conventional-failed.
  3. Mirikizumab for use in the treatment of CD according to claim 1, wherein the patient is biologic-experienced.
  4. Mirikizumab for use in the treatment of CD according to claim 1, wherein the patient is biologic-failed.
  5. Mirikizumab for use in the treatment of CD according to any one of claims 1-4, wherein three induction doses of mirikizumab are administered at about 4 week intervals and the first maintenance dose is administered about 4 weeks after the last induction dose is administered.

Description

This invention generally relates to mirikizumab, an antibody that binds to the p19 subunit of human IL-23 for use in the treatment of Crohn's Disease (CD). CD is a chronic disease of unknown etiology with environmental, genetic, and immunologic influences. Transmural inflammation affecting any part of the gastrointestinal tract from the mouth to the anus, usually appearing as discontinuous lesions, are normal characteristics for CD (Baumgart D C and Sandborn WJ, Lancet, Vol. 369, pages 1641-57, 2007). Symptoms include chronic diarrhoea (often bloody and containing pus or mucus), abdominal pain, weight loss, fever, fatigue, anaemia, rectal bleeding, and a feeling of fullness in the abdomen. Symptoms depend on the severity of the disease and location of the disease, with the majority of patients experiencing an abscess, fistula, stricture or an obstruction requiring surgical intervention. Relapsing-remitting symptoms, meaning that many patients have intermittent disease flares that are interspersed with periods of remission, is very common in CD (Lichtenstein G R et al., American Journal of Gastroenterology, Vol. 113, pages 481-517, 2018). Treatment goals in clinical practice are control of symptoms and healing of the intestinal mucosa. Treatment of autoimmune/inflammatory diseases with IL-23 targeted therapy is being pursued. The first such biologic to demonstrate clinical benefit in autoimmune disease was ustekinumab, which is a Food and Drug Administration (FDA)-approved monoclonal antibody for the treatment of psoriasis, psoriatic arthritis and CD. Ustekinumab binds the common p40 subunit of IL-12 and IL-23; therefore, it targets both cytokines, rather than IL-23 specifically. Blockade of the IL-12 pathway may prevent Th1 cell-induced interferon blockade of Th17 cell development, thus potentially limiting the clinical activity of p40 targeting antibodies. Experimental studies suggest that blocking the IL-23/Th17/IL-17 immune axis alone is sufficient to treat autoimmune inflammation (Monteleone G et al., Mediators of Inflammation, E-publication, 27 May 2009). Agents specifically targeting the IL-23 p19 subunit have demonstrated clinical activity in psoriasis (Sofen H et al., J Allergy Clin Immunol. Vol. 133, No. 4, pages 1032-1040, 2014; Kopp T et al., Nature, Vol. 521, No. 7551, pages 222-226, 2015; Krueger J G et al., J Allergy Clin Immunol., Vol. 136, No. 1, pages 116-124 e7, 2015). IL-23 p19-specific antibodies have also demonstrated clinical activity in CD (Sands B E et al., Gastroenterology, Vol. 148, No. 4, Supplement 1, S163-S164, Abstract 830, 2015; Feagan B G et al., Gastroenterology, Vol. 150, No. 4, Supplement 1, S 1266, Abstract 812a, 2016). Treatment regimens for CD with anti-IL-23p19 antibodies are disclosed in WO 2014/143540 Al, WO 2017/048901 Al and Ma, Christopher, et al. Expert Opinion on Investigational Drugs 27.8 (2018): 649-660. There remains a need for treatment options for CD that lead to favourable outcomes for patients, for example, in terms of efficacy, safety and/or tolerability of the treatment. In particular, there remains a need for treatment options in the form of dosage regimen of mirikizumab that provides optimal efficacy in the treatment of CD. Any reference to a method of treatment practiced on the human or animal body is to be interpreted as substances or compositions for use in such treatment. The present invention provides mirikizumab for use in the treatment of Crohn's Disease (CD) said treatment comprising: a) administering three induction doses of mirikizumab to the patient by intravenous injection, wherein each induction dose comprises about 900 mg of mirikizumab and wherein the three induction doses of mirikizumab are administered at about 4 week intervals; andb) administering maintenance dose(s) of mirikizumab to the patient by subcutaneous injection at about 4 week or about 8 week intervals, wherein the first maintenance dose is administered about 4 weeks or about 8 weeks after the last induction dose is administered and wherein each maintenance dose comprises 200 mg or 300 mg of mirikizumab, wherein the CD is moderate to severe CD. In some embodiments of the invention the patient is conventional-failed. In some embodiments of the invention the patient is biologic-experienced. In some embodiments of the invention the patient is biologic-failed. In some embodiments of the invention three induction doses of mirikizumab are administered at about 4 week intervals and the first maintenance dose is administered about 4 weeks after the last induction dose is administered. Accordingly, in a first aspect of the present disclosure, there is a provided a method for treating CD comprising administering mirikizumab to a patient, said method comprising: a) administering at least one induction dose of mirikizumab to the patient, wherein the induction dose comprises about 200 mg to about 1200 mg of mirikizumab; andb) administering at least one maintenance dose of mirikizumab t