- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Preclinical, Journal: Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C. (Pubmed Central) - Dec 16, 2021
Fecal microbiome and gene expression analyses of colonic tissue revealed dysbiosis, up-regulation of IFN-stimulated genes, and misregulation of genes associated with human IBD and animal models of colitis. This novel mouse model thus provides molecular insights into the multiple roles of intestinal epithelial cell cGMP, which culminate in dysbiosis and the induction of inflammation in the gut.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Trial initiation date: Efficacy of Linaclotide in Patients With Overlapping Functional Gastrointestinal Disorders (clinicaltrials.gov) - Dec 14, 2021
P4, N=78, Recruiting,
This novel mouse model thus provides molecular insights into the multiple roles of intestinal epithelial cell cGMP, which culminate in dysbiosis and the induction of inflammation in the gut. Initiation date: Aug 2021 --> Jan 2021
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, elobixibat (A3309) / Albireo, Ajinomoto, Ferring, Amitiza (lubiprostone) / Takeda, Mallinckrodt
Clinical, Retrospective data, Review, Journal: A Systematic Review and Network Meta-Analysis on the Efficacy of Medications in the Treatment of Chronic Idiopathic Constipation in Japan. (Pubmed Central) - Dec 13, 2021
Lubiprostone 48 μg was ranked first for the proportion of patients with SBM within 24 hours. Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.
- |||||||||| Review, Journal: Focus on Pharmacotherapy for Irritable Bowel Syndrome with Constipation. (Pubmed Central) - Nov 6, 2021
This article highlights the pivotal evidence for these agents and most recent treatment guidance from the major North American gastroenterological societies. When pharmaceuticals are used, a patient-specific approach based on efficacy, safety, tolerability, access, and affordability is recommended.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, Trulance (plecanatide) / Bausch Health
New P1 trial: GCC Agonist Signal in the Small Intestine (clinicaltrials.gov) - Nov 4, 2021
P1, N=39, Not yet recruiting,
- |||||||||| Clinical, Review, Journal: Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options. (Pubmed Central) - Oct 31, 2021
Among emerging agents, prucalopride, a prokinetic agent, is recommended as a second-line treatment in refractory CIC patients. In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, Trulance (plecanatide) / Bausch Health, Resolor (prucalopride) / J&J, Takeda
Journal, HEOR: Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis. (Pubmed Central) - Oct 29, 2021
In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available. Addressing costs at a policy level has the potential to enable patients and clinicians to move from navigating barriers in treatment access toward truly optimizing treatment choice.
- |||||||||| Clinical, Review, Journal: Evaluation and Treatment of Constipation in the Geriatric Population. (Pubmed Central) - Sep 22, 2021
Diagnostic algorithms should eliminate red-flag symptoms that may indicate a malignancy but also consider pelvic floor dysfunction, which is more common in this age group. An appropriate treatment plan is tailored to the severity of the patient's symptoms.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Enrollment change, Trial withdrawal: HygiRelief Procedure and HygiSample Evaluation for Functional Constipation (clinicaltrials.gov) - Sep 17, 2021
P=N/A, N=0, Withdrawn,
Effective strategies for managing opioid-induced and non-opioid-related constipation in patients with cancer include lifestyle, pharmacologic, and complementary approaches. N=40 --> 0 | Not yet recruiting --> Withdrawn
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Clinical, P3 data, Journal: Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System. (Pubmed Central) - Sep 15, 2021
Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.
- |||||||||| tamoxifen / Generic mfg.
A Disease of Many Names: Sclerosing Mesenteritis (Shoreline Exhibit Hall) - Sep 8, 2021 - Abstract #ACG2021ACG_2715;
There is no definitive therapy, but systemic steroids and antifibrotic agents such as tamoxifen have been studied; some patients require surgical resection.Figure: Figure 1. CT-Abdomen and Pelvis: An ovoid expansile region of mesenteric haziness within the central abdomen, encircling the mesenteric root vessels, reflecting sclerosing mesenteritis with mass effect on the surrounding bowel loops.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Time to Relief of Key Abdominal and Bowel Symptoms of Irritable Bowel Syndrome with Constipation: A Post-Hoc Analysis of Randomized Controlled Trials of Linaclotide (Shoreline Exhibit Hall) - Sep 8, 2021 - Abstract #ACG2021ACG_240;
P2, P3, P3
2350 patients (1172 PBO (mean age 44.7 years, 86.8% female) and 1178 LIN 290 µg (mean age 44.56 years, 86.8% female)) were included. For LIN-treated patients, median time to achieve responder definition was 3 weeks for abdominal pain and discomfort, and 4 weeks for bloating (vs. 6, 7, and 8 weeks, respectively for PBO).
- |||||||||| Xifaxan (rifaximin) / Alfa Wassermann, Bausch Health, Norgine, ASKA Pharma
Journal: Recent advances in the treatment of irritable bowel syndrome. (Pubmed Central) - Sep 8, 2021
The involvement of gastrointestinal microbiota constitutes a fascinating field of exploration as it offers the potential to be modulated by the use of probiotics, prebiotics, synbiotics as well as fecal microbiota transplantation. This review offers an updated overview on the recent advances in the treatment of IBS.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Journal: Oral pharmacological activation of hypothalamic guanylate cyclase 2C receptor stimulates brown fat thermogenesis to reduce body weight. (Pubmed Central) - Aug 29, 2021
Linaclotide exerts its actions through the central nervous system, and more specifically, via Gucy2c receptors located in the mediobasal hypothalamus, leading to the activation of the sympathetic nervous system to trigger the thermogenic activity of brown fat stimulating energy expenditure. These findings indicate for first time that, in addition to its effects at intestinal level to treat irritable bowel syndrome with constipation and chronic constipation, linaclotide also exerts a beneficial effect in whole body metabolism.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Journal: Improving the Gastrointestinal Stability of Linaclotide. (Pubmed Central) - Aug 27, 2021
All analogues had substantial improvements in gastrointestinal half-lives (>8 h vs linaclotide 48 min), and most remained active at low nanomolar concentrations. This work highlights strategic approaches for the development of gut-stable peptides toward the next generation of orally administered peptide drugs for the treatment of gastrointestinal disorders.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Trial completion date: Long-term Safety of Linaclotide in Pediatric Participants With FC or IBS-C (clinicaltrials.gov) - Aug 20, 2021
P3, N=120, Enrolling by invitation,
This work highlights strategic approaches for the development of gut-stable peptides toward the next generation of orally administered peptide drugs for the treatment of gastrointestinal disorders. Trial completion date: Dec 2023 --> Jul 2024
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
[VIRTUAL] COMPARISON OF 1-L PEG PLUS ASCORBIC ACID WITH LINACLOTIDE VERSUS SENNOSIDE FOR COLON CLEANING IN CONSTIPATED PATIENTS (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_2490;
Linaclotide prior to 1-L PEG-Asc regimen significantly increased efficacy of bowel preparation and adenoma detection rate compared to sennoside regimen without reducing tolerability in constipated patients. Linaclotide prior to 1-L PEG-Asc regimen significantly increased efficacy of bowel preparation and adenoma detection rate compared to sennoside regimen without reducing tolerability in constipated patients.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
[VIRTUAL] COMPARISON OF 1-L PEG PLUS ASCORBIC ACID WITH LINACLOTIDE VERSUS SENNOSIDE FOR COLON CLEANING IN CONSTIPATED PATIENTS (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_659;
Linaclotide prior to 1-L PEG-Asc regimen significantly increased efficacy of bowel preparation and adenoma detection rate compared to sennoside regimen without reducing tolerability in constipated patients. Linaclotide prior to 1-L PEG-Asc regimen significantly increased efficacy of bowel preparation and adenoma detection rate compared to sennoside regimen without reducing tolerability in constipated patients.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, Ibsrela (tenapanor) / Ardelyx, Kyowa Kirin, Knight Therap, Amitiza (lubiprostone) / Takeda, Mallinckrodt
Preclinical, Journal: Linaclotide, lubiprostone and tenapanor improve gut fluidity and alkalinity in CFTR-deficient and F508del mutant mice via NHE3 inhibition. (Pubmed Central) - Jul 7, 2021
Linaclotide, lubiprostone and tenapanor reduced fluid absorption and increased alkaline output in the CF gut. Their application may ameliorate constipation and reduce obstructive episodes in CF patients.
- |||||||||| Xifaxan (rifaximin) / Alfa Wassermann, Bausch Health, Norgine, ASKA Pharma
Clinical, Journal: Contrasting Clinician and Insurer Perspectives to Managing Irritable Bowel Syndrome: Multilevel Modeling Analysis. (Pubmed Central) - Jun 22, 2021
From an insurer perspective, routine and algorithmic prescription drug coverage restrictions requiring failure of low-cost behavioral, dietary, and off-label treatments appear cost-effective. Efforts to address insurance coverage and drug pricing are needed so that healthcare providers can optimally care for patients with this common, heterogenous disorder.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Clinical, Journal: Efficacy and Safety of Linaclotide in Elderly Patients (Pubmed Central) - May 21, 2021
Linaclotide is effective and safe for use in elderly patients. The incidence of diarrhea may increase when linaclotide is administered alone or concurrently used with medications that cause constipation.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Journal: Linaclotide for the treatment of refractory lower bowel manifestations of systemic sclerosis. (Pubmed Central) - May 15, 2021
Linaclotide is a well-tolerated and efficacious pro-secretory and pro-motility agent that can be used to manage refractory lower GI manifestations in SSc. We found that low-dose linaclotide is an effective option and may be better tolerated, though a subset of patients may require high dose regimens.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Trial completion date, Trial primary completion date: Efficacy of Linaclotide in Type II Diabetics With Chronic Constipation (clinicaltrials.gov) - Apr 22, 2021
P4, N=23, Active, not recruiting,
Linaclotide significantly improved OIC symptoms and was well tolerated in patients with chronic noncancer pain. Trial completion date: Jan 2021 --> Dec 2021 | Trial primary completion date: Oct 2020 --> Oct 2021
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Clinical, Journal: Lessons learned: Chronic idiopathic constipation patient experiences with over-the-counter medications. (Pubmed Central) - Apr 22, 2021
P3
Trial completion date: Jan 2021 --> Dec 2021 | Trial primary completion date: Oct 2020 --> Oct 2021 Treatment effects on individual CIC symptoms, predictability of bowel habits, and satisfaction with treatment are all important factors for healthcare providers and patients to consider when establishing an effective treatment regimen for CIC.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
[VIRTUAL] ABBVIE/IRONWOOD (LINZESS) (DDW Virtual) - Apr 19, 2021 - Abstract #DDW2021DDW_5024;
Treatment effects on individual CIC symptoms, predictability of bowel habits, and satisfaction with treatment are all important factors for healthcare providers and patients to consider when establishing an effective treatment regimen for CIC. Sponsor: Abbvie, Ironwood
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Preclinical, Journal: Changes of guanylate cyclase C in colon tissues of rats with intestinal injury associated with severe acute pancreatitis (Pubmed Central) - Apr 16, 2021
Another 18 SD rats were randomized into 3 groups for sham operation, SAP modeling or intragastric administration of linaclotide (a GC-C agonist) solution once daily at the dose of 10 μg/kg...In rats with SAP-related intestinal injury, the expression of GC-C in the colon tissue decreases to the lowest level at 12 h after SAP onset followed by gradual increase. activating GC-C can increase the expression levels of GC-C and claudin-1 and alleviate intestinal injury, suggesting the role of GC-C in maintaining intestinal barrier integrity by regulating the expression of tight junction proteins.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, recombinant parathyroid hormone (PTH-1-34) / Novartis, Novo Nordisk
Journal: Numaswitch: an efficient high-titer expression platform to produce peptides and small proteins. (Pubmed Central) - Mar 26, 2021
Numaswitch was successfully employed for the production of diverse peptides and small proteins varying in length, physicochemical and functional characteristics, including Teriparatide, Linaclotide, human β-amyloid and Serum amyloid A3. Additionally, the potential of Numaswitch for a cost-efficient commercial production is demonstrated yielding > 2 g Teriparatide per liter fermentation broth in a quality meeting API standard.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
[VIRTUAL] IMPROVEMENT IN ABDOMINAL SYMPTOMS WITH LINACLOTIDE IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH CONSTIPATION: RESULTS FROM A PHASE 3B TRIAL () - Mar 25, 2021 - Abstract #CDDW2021CDDW_330;
These support the effectiveness of LIN for improving a spectrum of abdominal symptoms in IBS-C.Open in new tabDownload slide(A) LSM CFB over 12 weeks in abdominal symptoms and (B) 6/12-week responder rates in the LIN and PBO treatment groups.A 6/12-week APC+1 responder was a patient who met the weekly APC+1 responder criteria for ≥6 of 12 weeks; a weekly APC+1 responder was a patient who had an increase from baseline of ≥1 in complete spontaneous bowel movement weekly rate and a decrease from baseline of ≥30% in weekly abdominal pain score. Baseline scores for abdominal symptoms were as follows: bloating (LIN: 6.595; PBO: 6.602); pain (LIN: 6.266, PBO: 6.245); discomfort (LIN: 6.430, PBO: 6.462).Open in new tabDownload slide(A) LSM CFB over 12 weeks in abdominal symptoms and (B) 6/12-week responder rates in the LIN and PBO treatment groups.A 6/12-week APC+1 responder was a patient who met the weekly APC+1 responder criteria for ≥6 of 12 weeks; a weekly APC+1 responder was a patient who had an increase from baseline of ≥1 in complete spontaneous bowel movement weekly rate and a decrease from baseline of ≥30% in weekly abdominal pain score.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
[VIRTUAL] LINACLOTIDE IS NOT DETECTABLE IN BREAST MILK OF LACTATING WOMEN: AN OPEN-LABEL, PHASE 1 STUDY () - Mar 25, 2021 - Abstract #CDDW2021CDDW_329;
P1
Baseline scores for abdominal symptoms were as follows: bloating (LIN: 6.595; PBO: 6.602); pain (LIN: 6.266, PBO: 6.245); discomfort (LIN: 6.430, PBO: 6.462).Open in new tabDownload slide(A) LSM CFB over 12 weeks in abdominal symptoms and (B) 6/12-week responder rates in the LIN and PBO treatment groups.A 6/12-week APC+1 responder was a patient who met the weekly APC+1 responder criteria for ≥6 of 12 weeks; a weekly APC+1 responder was a patient who had an increase from baseline of ≥1 in complete spontaneous bowel movement weekly rate and a decrease from baseline of ≥30% in weekly abdominal pain score. The data collected in this study provide no evidence that breastfeeding infants receive LIN or MM-419447 through breast milk as their concentrations were below the quantitation limit following multiple once-daily doses of LIN 72 μg, 145 μg, or 290 μg.
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