Linzess DR (linaclotide DR) / Ironwood Pharma, AbbVie - LARVOL DELTA

Randomised clinical trial: effects of MD-7246 on irritable bowel syndrome with diarrhoea. (PubMed, Aliment Pharmacol Ther) - "MD-7246 at the doses studied did not improve abdominal pain relative to placebo in an IBS-D patient population. Similarly, most additional efficacy endpoints showed no improvement with MD-7246 relative to placebo."

Journal • Gastrointestinal Disorder • Immunology • Pain

[VIRTUAL] IMPACT OF MD-7246 ON IRRITABLE BOWEL SYNDROME WITH DIARRHEA: PHASE 2 RESULTS (DDW 2021) - "Background: MD-7246 is a new formulation of linaclotide designed to be released near the ileocecal junction...Patients were provided rescue loperamide to control diarrhea... MD-7246 did not show significant benefit when compared to placebo in patients with IBS-D. The effect seen in the subset of patients with longer diagnosis time is intriguing and should be explored further."

P2 data • Constipation • Gastrointestinal Disorder • Immunology • Pain

A Study of MD-7246 to Treat Abdominal Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (clinicaltrials.gov) - P2; N=515; Completed; Sponsor: Ironwood Pharmaceuticals, Inc.; N=388 ➔ 515

Clinical • Enrollment change • Gastrointestinal Disorder • Immunology • Pain

Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation. (PubMed, Am J Gastroenterol) - "Altering the site of drug delivery in the intestine might uncouple linaclotide's pain relief from secretory effects. Persistent, modest abdominal pain improvement with limited impact on bowel symptom parameters, as seen across MD-7246 doses, warrants further study of MD-7246 as a novel treatment for abdominal pain, regardless of IBS subtype."

Clinical • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Pain

A Study of MD-7246 to Treat Abdominal Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (clinicaltrials.gov) - P2; N=388; Completed; Sponsor: Ironwood Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Sep 2020 ➔ Mar 2020; Trial primary completion date: Sep 2020 ➔ Feb 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Immunology • Pain

Trial of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C) (clinicaltrials.gov) - P2b; N=759; Completed; Sponsor: Ironwood Pharmaceuticals, Inc.; N=532 ➔ 759

Clinical • Enrollment change • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology

Ironwood Pharmaceuticals reports strong fourth quarter and full year 2019 results, exceeding full year 2019 guidance; provides full year 2020 guidance (Businesswire) - "Ironwood and Allergan completed enrollment in a Phase II clinical trial of MD-7246 in patients suffering from abdominal pain associated with IBS with diarrhea (IBS-D). Ironwood continues to target top-line data from the Phase II trial in mid-2020."

P2 data

A Study of MD-7246 to Treat Abdominal Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (clinicaltrials.gov) - P2; N=388; Active, not recruiting; Sponsor: Ironwood Pharmaceuticals, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

MD-7246, a Delayed-Release Formulation of Linaclotide Targeting Visceral Pain Associated With IBS-D, Does Not Impact Bowel Frequency or Stool Consistency in Healthy Volunteers: Results From Phase I Trial (ACG 2019) - "Placebo, low, mid, or high doses of MD-7246 were received by 6 subjects each. Neither LIN nor its active metabolite were detected in plasma after 7 days of oral administration and no intact tablets were discovered in any subject’s stool. The median and interquartile range (IQR) for change from baseline (CFB) in SBM and BSFS were similar and overlapping for placebo and all 3 MD-7246 dose groups (median (IQR) CFB: SBM: -2.6 (-4.6, 2.9), -1.9 (-4.4, -1.4), -1.3 (-2.0, 0.0), and 0.0 (‑7.7, 0.9); BSFS: 0.4 (-0.2, 1.0), 0.2 (-1.0, 0.9), 0.2 (-0.4, 1.0) and 0.4 (-0.3, 1.8) in placebo and low, mid, and high MD-7246 doses, respectively)."

Clinical • P1 data

Ironwood Pharmaceuticals reports third quarter 2019 results; raises full year 2019 guidance (Businesswire) - "LINZESS U.S. net sales...were $214.7 million in the third quarter of 2019, a 5% increase compared to LINZESS net sales reported by Allergan in the third quarter of 2018....Total LINZESS prescription demand in the third quarter of 2019 included approximately 34 million LINZESS capsules...Ironwood and Allergan filed a lawsuit in November 2016 against certain generic drug manufacturers...The stipulation and order provide for the rescheduled trial to begin on January 7, 2020....MD-7246: Ironwood and Allergan are currently enrolling patients in a Phase II clinical trial of MD-7246 for the potential treatment of abdominal pain associated with IBS with diarrhea (IBS-D). Due to faster than expected enrollment, top-line data from the Phase II trial are now expected in mid-2020 versus previous guidance of the second half of 2020."

Corporate lawsuit • Enrollment status • P2 data • Sales

Ironwood Pharmaceuticals and Allergan initiate patient dosing in phase II clinical trial of MD-7246 in patients with abdominal pain associated with IBS-D (Businesswire) - "Ironwood Pharmaceuticals, Inc....today announced the initiation of patient dosing in a Phase II clinical trial evaluating MD-7246 in patients with abdominal pain associated with irritable bowel syndrome with diarrhea (IBS-D). Data from the Phase II trial are expected in the second half of 2020....The study is expected to enroll approximately 400 IBS-D patients who are randomized equally across three dose levels of MD-7246 (300, 600 or 1,200 mcg), or matching placebo, administered once daily."

Enrollment status • P2 data • Trial status