Airtight container

Protect from light

Airtight container

Protect from light

Limited published evidence of safety

Only negligible amounts in breast milk

Used in infants >1 month

No published evidence of safety after oral or rectal administration

Low levels anticipated in milk due to the drug’s properties

Jan 20 · Budenofalk 3mg gastro-resistant capsules are now licensed for use in microscopic colitis, both induction and maintenance of remission (previously licensed for induction of remission of active collagenous colitis, a form of microscopic colitis) [6].

Dec 19 · Licence change approved via the EU decentralised procedure, including in the UK. The SPC has been updated with the change in indication from collagenous colitis to microscopic colitis, with consequential changes to the posology and clinical efficacy and safety section to include data on the maintenance of remission in collagenous colitis [6].

Jan 19 · Currently pre-registration in EU. Has been filed via the decentralised procedure [5].

Apr 17 · Currently in PIII trials. Will be filed in the EU using the decentralised procedure [2].

Microscopic colitis (MC) is a chronic inflammatory condition characterized by chronic diarrhea, normal colonic mucosa, and abnormal histologic hallmarks. Two distinct disease phenotypes exist, collagenous colitis (CC) and lymphocytic colitis (LC). Reported prevalence rates of CC and LC are 42 and 69 per 100,000 persons, respectively [1].

Sep 13 · Dr Falk Pharma in collaboration with the Swedish Organization for Studies on Inflammatory Bowel Disease completed the PIII SOIBD Collagenous Colitis Maintenance Study (SCCMS) to investigate efficacy and tolerability of budesonide gastro-resistant granule in patients with microscopic colitis. Patients underwent an 8-week induction phase followed by maintenance treatment phase (NCT01278082). The trial enrolled 92 patients in Belgium, the Czech Republic, Denmark, Germany, Hungary and Sweden [2,4].

Nov 20 · Licence extension approved by the MHRA for induction of remission in adults with active microscopic colitis, in a dose of one 9mg tablet once daily for up to 8 weeks [2].

Microscopic colitis is an inflammatory bowel disease (IBD) that affects the large bowel - the colon and rectum. At least 1 in 1000 people are thought to have microscopic colitis in the UK, but the real number could be a lot higher because it is often underreported and misdiagnosed [1].

Nov 20 · Evidence for the indication microscopic colitis (collagenous colitis and lymphocytic colitis) comes from studies on budesonide product Entocort. The systemic availability of this product is similar to that of budesonide product Cortiment. Two randomised, double-blind, placebo-controlled induction studies of six and eight weeks duration investigated the clinical and histological effects of budesonide 9 mg/day in the treatment of collagenous colitis. In the first study, 23 patients were randomised to budesonide 9 mg/day and 22 patients to placebo for 6 weeks. The rate of clinical remission was significantly higher (p<0.001) in the budesonide group than in the placebo group 86.9% vs. 13.6%. Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in one patient of the placebo group (4.5%; p<0.001). In the second study, 10 patients were randomised to budesonide for 8 weeks (9 mg/day 4 weeks, 6 mg/day 2 weeks, and 3 mg/day 2 weeks) and ten to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). Two open-label studies (run-in phase of randomised, double-blind, placebo-controlled maintenance studies) investigated the efficacy of budesonide 9 mg/day during 6 weeks. In the first study, 46 patients (96%) achieved clinical remission within 2–30 (mean 6.4) days, with marked improvements in stool consistency. In the second study, of the 42 patients who commenced the study, 34 patients (81%) were in clinical remission (mean stool frequency of three or fewer per day) at week 6. Evidence for lymphocytic colitis is limited. One randomised, double-blind placebo-controlled study was carried out in 15 lymphocytic colitis patients. Eleven subjects were treated with budesonide 9 mg/day and four patients received placebo for 8 weeks. A clinical response (defined as at least 50% improvement in the frequency of bowel movements) was seen in 25% of the placebo group vs. 91% in the budesonide group (p=0.03) [2].

May 20 · New 0.5mg strength of the orodispersible Jorveza formulation and licence extension for maintenance therapy approved in EU [4].

Mar 20 · CHMP issues a positive opinion recommending a change to the duration of treatment allowing the use of Jorveza as maintenance therapy for eosinophilic esophagitis in adults (older than 18 years of age) with a new strength (0.5 mg orodispersible tablet). The recommendation for maintenance therapy is as follows: The recommended daily dose is 1 mg budesonide as one 0.5‑mg-tablet in the morning and one 0.5‑mg-tablet in the evening or 2 mg budesonide as one 1‑mg-tablet in the morning and one 1‑mg-tablet in the evening, depending on the individual clinical requirement of the patient. A maintenance dose of 1 mg budesonide twice daily is recommended for patients with a long standing disease history and/or high extent of esophageal inflammation in their acute disease state. The duration of maintenance therapy is determined by the treating physician [3].

In 2013, eosinophilic oesophagitis was considered to affect less than 5 in 10,000 people in the EU [1]. Studies suggest that the prevalence is rising, but it is uncertain whether this is a true increase or due to better diagnosis; it is most common in middle-aged men [2].

NICE scope

SMC

Microscopic colitis is characterised by chronic watery diarrhoea of unknown origin. Colonoscopy shows an essentially normal colonic mucosa, however abnormal histopathology on biopsy helps establish the correct diagnosis. Collagenous colitis and lymphocytic colitis are the two major subtypes. True incidence not known.

NIHR

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon that follows a course of relapse and remission. In distal disease (left-sided colitis), colitis is confined to the rectum (proctitis) or rectum and sigmoid colon (proctosigmoiditis). UC has an incidence in the UK of approximately 10 per 100,000 people annually and a prevalence of approximately 240 per 100,000 [1].

IgA nephropathry is the most common primary glomerular disease with approximately 30% to 40% of patients progressing to end-stage kidney disease (ESKD) within 20 years. It is uncommon below the age of 10 and 80% of cases are diagnosed between the ages of 16 and 35 [1].

In 2013, eosinophilic oesophagitis was considered to affect less than 5 in 10,000 people in the EU [1]. Studies suggest that the prevalence is rising, but it is uncertain whether this is a true increase or due to better diagnosis; it is most common in middle-aged men [2].

Dec 20 · FDA has accepted for review the company’s New Drug Application and granted Priority Review for the investigational therapy budesonide oral suspension (TAK-721)[9].

Feb 20 · According to its latest financial results, Takeda is only developing TAK-721 for the US market [8].

Eosinophilic oesophagitis affects less than 5 in 10,000 people in the EU [1].

Oct 19 · PIII study of budesonide oral suspension in eosinophilic oesophagitis completes meets co-primary efficacy endpoints; the RCT (NCT02605837; n=318) found significantly more histologic responders and dysphagia symptom responders in the budesonide oral suspension treated group versus the placebo-treated group (53.1% vs 1.0%, p<0.001; 52.6% vs 39.1%, p=0.024, respectively) after an initial 12 weeks of therapy [6].

Apr 19 · PIII extension study (NCT02736409) is ongoing and has completed recruitment. Collection of primary outcome data is expected to complete Nov 19 [5].

Jan 19 · PIII study (NCT02605837) completes [5].

Jan 18 · PIII study (NCT02605837) is still recruiting, & expects to complete collection of primary outcome data in Jun 18 [3]

Oct 17 · PIII extension trial to study safety of budesonide oral suspension in patients with eosinophilic oesophagitis and participated in SHP621-302 study starts (SHP621-303; NCT03245840). The open-label trial intends to enrol approximately 100 patients in the US [2].

Apr 16 · PIII ORBIT2 extension trial to assess the maintenance of efficacy of budesonide oral suspension (10ml of 0.2 mg/ml) in adolescent and adult patients with EoE and who have completed the SHP621-301/NCT02605837 induction study starts (SHP621-302; NCT02736409). The trial is recruiting 200 patients (aged 11 to 55 years) in the US [2].

Nov 15 · PIII trial to assess the safety and efficacy of budesonide oral suspension (10ml of 0.2 mg/ml) in adolescent and adult patients with eosinophilic oesophagitis (EoE) dysphagia starts (NCT02605837). Histologic response and dysphagia symptom response will be assessed after 16 weeks of treatment as the primary endpoints. The trial is expected to enrol approximately 300 patients (aged 11 to 55 years) in the US [2].