Jump to content
Advertisement

Advertisement
Jeffrey Roberts

FDA approves Motegrity™ (prucalopride) for Chronic Idiopathic Constipation (CIC)

Recommended Posts

Jeffrey Roberts

FDA approves Motegrity™ (prucalopride) for Chronic Idiopathic Constipation (CIC)

Motegrity™ is a much needed drug for the relief of constipation sufferers 

(PRWEB) December 17, 2018 -- Following the announcement of the United States Food and Drug Administration's (FDA) approval of Motegrity™ (prucalopride), a serotonin-4 receptor agonist for adults with Chronic Idiopathic Constipation (CIC), Jeffrey Roberts, Founder of the IBS Patient Support Group, commented:

"Motegrity™ is a much needed medication for sufferers of constipation. The IBS Patient Support Group is very grateful for the decision that the FDA has made in approval of this medicine. We have been working for the approval of this medicine based on the relief of symptoms of bloating, pain and constipation, that we have heard about from patients." A member of the IBS Patient Support Group told us that "People who do not deal with chronic constipation have no concept of how it can destroy your life, personal relationships, brain health and ability to work - it's an absolutely miserable problem that affects all other areas of your health." Jeffrey Roberts presented testimony to the FDA Gastrointestinal Drugs Advisory Committee on October 18, 2018 in support of Motegrity™.

Background on Motegrity™ (prucalopride):

Motegrity™ is a selective serotonin-4 (5-HT4) receptor agonist, which provides a different class of treatment for CIC that works by enhancing colonic peristalsis to increase bowel motility. The efficacy of once-daily treatment with Motegrity was evaluated in six double-blind, placebo-controlled, randomized, multicenter clinical studies lasting 12 weeks or 24 weeks. Of the 2,484 patients, most were female (76%) and Caucasian (76%), with an average age of 47 (+/- 16 years). During studies, significantly more patients taking Motegrity™ achieved an average of ≥3 complete spontaneous bowel movements per week over 12 weeks.

About the IBS Patient Support Group:

The IBS Patient Support Group was established by Jeffrey Roberts who was the founder of the first Irritable Bowel Syndrome patient community website in 1995. The IBS Patient Support Group community was launched as a public education advocacy community for sufferers and believes in evidenced-based medicine and non-anecdotal treatment options for patients. Jeffrey Roberts has been an Irritable Bowel Syndrome sufferer for over 25+ years and has worked closely with researchers, industry and patients for over 30 years.

###

Contact:

IBS Patient Support Group
Jeffrey Roberts, Founder 
jeffrey.roberts@ibspatient.org
203-424-0660
https://www.ibspatient.org

Share this post


Link to post
Share on other sites

Advertisement

Advertisement
Jeffrey Roberts

FDA approves Shire’s Motegrity™ (prucalopride), the only serotonin-4 receptor agonist for adults with Chronic Idiopathic Constipation (CIC)

  • Unlike other prescription CIC treatments, Motegrity works differently by enhancing natural movements of the colon muscle, known as peristalsis1,2
  • Motegrity was shown to help normalize complete spontaneous bowel movement frequency (avg. ≥3 CSBMs/week over 12 weeks) across five of six controlled clinical studies1

Cambridge, Mass. – December 17, 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG) has announced that the U.S. Food and Drug Administration (FDA) has approved Motegrity™ (prucalopride), a once-daily, oral treatment option for adults with Chronic Idiopathic Constipation (CIC).1

Motegrity, a selective serotonin-4 (5-HT4) receptor agonist, provides a different class of treatment for CIC that works by enhancing colonic peristalsis to increase bowel motility.1-3 Motegrity is expected to launch in 2019 in the United States, where an estimated 35 million adults are living with CIC.4,5* While not all patients may be right for treatment, Motegrity represents an important new option.

“The approval of Motegrity marks a new day in the treatment of CIC,” said Howard Mayer, M.D., Senior Vice President and Chief Medical Officer, Shire. “This significant milestone reinforces our continued commitment to the GI community and advances our goal of addressing the unmet need of patients suffering from rare, specialized and common GI conditions.” 

The efficacy of once-daily treatment with Motegrity was evaluated in six double-blind, placebo-controlled, randomized, multicenter clinical studies lasting 12 weeks (studies 1-5) or 24 weeks (study 6).1 Of the 2,484 patients, most were female (76%) and Caucasian (76%), with an average age of 47 (+/- 16 years).1

“As a gastroenterologist, it’s important for me to help patients with CIC find a treatment that works well for them,” said Brooks Cash, M.D., Chief of the Division of Gastroenterology, Hepatology, and Nutrition at the University of Texas Health Science Center at Houston. “It’s exciting to be able to now offer my patients a new treatment option that addresses colonic peristalsis.”  

During studies, significantly more patients taking Motegrity achieved the primary endpoint (an average of ≥3 complete spontaneous bowel movements [CSBMs] per week over 12 weeks, considered normalization of BM frequency) than those in the placebo group (19-38% Motegrity ≤2 mg vs. 10-20% placebo) across five of six trials. A rapid response was seen with Motegrity as early as week 1, with improvements maintained throughout 12 weeks of treatment.1 The FDA has requested that Shire conduct five post-marketing studies evaluating the pharmacokinetics, efficacy, and safety of Motegrity in pediatric patients with CIC (6 months old to less than 18 years of age) and pregnant and lactating women with CIC treated with Motegrity.6 

Motegrity is contraindicated in patients with a history of hypersensitivity to Motegrity. Reactions include dyspnea, rash, pruritus, urticaria, and facial edema have been observed. Motegrity is also contraindicated in patients with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn’s disease, ulcerative colitis, and toxic megacolon/megarectum.1 

In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established. Monitor all patients treated with Motegrity for persistent worsening of depression or the emergence of suicidal thoughts and behaviors. Counsel patients, their caregivers, and family members of patients to be aware of any unusual changes in mood or behavior and alert the healthcare provider. Instruct patients to discontinue Motegrity immediately and contact their healthcare provider if they experience any of these symptoms.1 

Most common adverse reactions (≥2%) are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence and fatigue.1 Overall, discontinuation due to adverse events was low (5% Motegrity 2 mg once daily; 3% placebo). If reported, adverse events of diarrhea or headache typically resolved within a few days.1 In addition, cardiovascular safety was evaluated in a MACE (major adverse cardiovascular events) analysis of the double-blind, placebo-controlled and open-label studies. It was also assessed in a retrospective observational study, which demonstrated no increase in the risk of MACE with Motegrity relative to polyethylene glycol (PEG).1

CIC is a common condition affecting roughly 14% of the adult population.4,5 Symptoms can range from straining and bloating, to infrequent, or incomplete bowel movements.7 While “idiopathic” by definition (meaning the exact cause is not known), it is believed that CIC may be caused by insufficient movement of the colon muscle.7

Important Safety Information

Contraindications
Motegrity is contraindicated in patients with:

  • A history of hypersensitivity to Motegrity. Reactions include dyspnea, rash, pruritus, urticaria, and facial edema have been observed.
  • Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn’s disease, ulcerative colitis, and toxic megacolon/megarectum

Warnings and Precautions
In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established.

Monitor all patients treated with Motegrity for persistent worsening of depression or the emergence of suicidal thoughts and behaviors. Counsel patients, their caregivers, and family members of patients to be aware of any unusual changes in mood or behavior and alert the healthcare provider. Instruct patients to discontinue Motegrity immediately and contact their healthcare provider if they experience any of these symptoms. 

Adverse Reactions
Most common adverse reactions (≥2%) are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence and fatigue.1 Overall, discontinuation due to adverse events was low (5% Motegrity 2 mg once daily; 3% placebo). If reported, adverse events of diarrhea or headache typically resolved within a few days.1 In addition, cardiovascular safety was evaluated in a MACE† (major adverse cardiovascular events) analysis of the double-blind, placebo-controlled and open-label studies. It was also assessed in a retrospective observational study, which demonstrated no increase in the risk of MACE with Motegrity relative to polyethylene glycol (PEG).1

Use in Specific Populations

  • Lactation: Motegrity is present in breast milk. Consider risks and benefits of breastfeeding. 
  • Pediatric: Safety and effectiveness in pediatric patients have not been established.
  • Renal Impairment: A decreased dosage is recommended in patients with severe renal impairment. Avoid Motegrity in patients with end stage renal disease requiring dialysis.

For additional information, click for full Prescribing Information.

For further information please contact:

Investor Relations    
Christoph Brackmann christoph.brackmann@shire.com +41 41 288 41 29
Sun Kim sun.kim@shire.com +1 617 588 8175
Scott Burrows scott.burrows@shire.com +41 41 288 4195
Media  
Katie Joyce kjoyce@shire.com +1 781 482 2779

NOTES TO EDITORS

About Shire

Shire is the global biotechnology leader serving patients with rare diseases and specialized conditions. We seek to push boundaries through discovering and delivering new possibilities for patient communities who often have few or no other champions. Relentlessly on the edge of what’s next, we are serial innovators with a diverse pipeline offering fresh thinking and new hope. Serving patients and partnering with healthcare communities in over 100 countries, we strive to be part of the entire patient journey to enable earlier diagnosis, raise standards of care, accelerate access to treatment, and support patients. Our diverse portfolio of therapeutic areas includes Immunology, Hematology, Genetic Diseases, Neuroscience, Internal Medicine, and Ophthalmics. 

Championing patients is our call to action - it brings the opportunity - and responsibility - to change people’s lives. 

www.shire.com

Forward-Looking Statements

Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, projected revenues, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:

  • Shire’s products may not be a commercial success; 
  • increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire’s future revenues, financial condition and results of operations; 
  • Shire depends on third parties to supply certain inputs and services critical to its operations including certain inputs, services and ingredients critical to its manufacturing processes. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time; 
  • the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches; 
  • the nature of producing plasma-based therapies may prevent Shire from timely responding to market forces and effectively managing its production capacity; 
  • Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval; 
  • the actions of certain customers could affect Shire’s ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial conditions or results of operations; 
  • failure to comply with laws and regulations governing the sales and marketing of its products could materially impact Shire’s revenues and profitability; 
  • Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics; 
  • Shire’s patented products are subject to significant competition from generics; 
  • adverse outcomes in legal matters, tax audits and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on Shire’s revenues, financial condition or results of operations; 
  • Shire may fail to obtain, maintain, enforce or defend the intellectual property rights required to conduct its business; 
  • Shire faces intense competition for highly qualified personnel from other companies and organizations; 
  • failure to successfully execute or attain strategic objectives from Shire’s acquisitions and growth strategy may adversely affect Shire’s financial condition and results of operations; 
  • Shire’s growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products; 
  • a slowdown of global economic growth, or economic instability of countries in which Shire does business, could have negative consequences for Shire’s business and increase the risk of non-payment by Shire’s customers; 
  • changes in foreign currency exchange rates and interest rates could have a material adverse effect on Shire’s operating results and liquidity; 
  • Shire is subject to evolving and complex tax laws, which may result in additional liabilities that may adversely affect Shire’s financial condition or results of operations; 
  • if a marketed product fails to work effectively or causes adverse side effects, this could result in damage to Shire’s reputation, the withdrawal of the product and legal action against Shire; 
  • Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire’s revenues, financial condition or results of operations; 
  • Shire faces risks relating to the expected exit of the United Kingdom from the European Union; 
  • Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs and may decrease its business flexibility; 
  • the potential uncertainty among our employees, customers, suppliers, and other business partners resulting from the announcement by Takeda Pharmaceutical Company Limited on May 8, 2018 of a recommended offer for Shire under the UK Takeover Code; and 

a further list and description of risks, uncertainties and other matters can be found in Shire’s most recent Annual Report on Form 10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in “ITEM1A: Risk Factors”, and in Shire’s subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire’s website.

All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.

*This represents ~14% of the U.S. population as of July 1, 2017 Census Bureau Data.4

Major adverse cardiovascular events (MACE) is defined as cardiovascular death; nonfatal myocardial infarction; and nonfatal stroke. 

References
1. Motegrity™ (prucalopride) Prescribing Information. Lexington, MA; Shire LLC; 2018.
2. Camilleri M, Ford AC, Mawe GM, et al. Nat Rev Dis Primers.2017;3:17095.
3. Tack J, Camilleri M, Chang L, et al. Aliment Pharmacol Ther. 2012:35(7):745-767. 
4. U.S. Census Bureau. Quick Facts (2017). https://www.census.gov/quickfacts/fact/table/US/PST045216. 
5. Suares NC, Ford AC. Am J Gastroenterol. 2011;106(9):1582-1591. 
6. Motegrity (prucalopride) FDA NDA Approval Letter, December 2018
7. Lacy BE, Mearin F, Chang L, et al. Gastroenterology 2016;150:1393–1407.

https://www.shire.com/en/newsroom/2018/december/qmmwqk

Share this post


Link to post
Share on other sites
Jeffrey Roberts

I've been told that the acquisition of Shire by Takeda should not slow down the launch of Motegrity (prucalopride).

Takeda Completes Acquisition of Shire, Becoming a Global, Values-based, R&D-Driven Biopharmaceutical Leader

 

− 8 months from deal announcement to deal close
− Strong shareholder support with high approval rates on Takeda (89.1%) and Shire (99.8%)
− Integration planning well underway

OSAKA, JAPAN, January 8, 2019 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced the completion of its acquisition of Shire plc (“Shire”), becoming a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan.

Takeda now has an attractive, expanded geographic footprint and leading position in Japan and the U.S., bringing its highly-innovative medicines to approximately 80 countries/regions with dedicated employees worldwide. Takeda’s R&D efforts are focused on its four therapeutic areas of Oncology, Gastroenterology (GI), Neuroscience and Rare Diseases, with targeted R&D investment also committed to Plasma-Derived Therapies (PDT) and Vaccines. Takeda's strengthened, highly innovative R&D engine enables the company to have a more global, robust and modality-diverse pipeline as well as to focus on breakthrough innovation. 

The combined annual revenue of the company, exceeding $30 billion USD, is mainly derived from the key business areas of Oncology, GI, Neuroscience, Rare Diseases and PDT.

“We are delighted that the acquisition was approved by an overwhelming majority of our shareholders at Takeda's extraordinary general meeting on December 5th, 2018. We are also pleased to have completed the acquisition several months earlier than expected, which was enabled through the hard work of our respective organizations and the smooth receipt of regulatory clearances,” said Christophe Weber, President and Chief Executive Officer of Takeda. “We appreciate the support of our employees, partners and shareholders throughout the process. This marks a significant moment in Takeda’s history and is an exciting step forward as we accelerate our transformation journey to deliver highly-innovative medicines to patients around the world with expanded scale and geographical footprint.”

Weber continued, “The execution of our integration begins today, and we are confident in our ability to execute a smooth integration under the leadership of our experienced and diverse Takeda Executive Team with a strong track record. The Operating Model we established in September last year has set a clear framework for our integration plans, and we have a highly skilled and dedicated integration team leading the process.”

In order to fund the acquisition, Takeda has secured permanent financing with highly competitive rates, resulting in an overall blended interest rate for Takeda's total debt of approximately 2.3%. The company is confident that it will retain its investment grade credit rating and return to a net debt to EBITDA ratio of 2.0x or less within three to five years following completion.

Weber will present at the J.P. Morgan Healthcare Conference at 3:30 p.m. PST on January 8, 2019.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience and Rare Diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions.

For more information, visit https://www.takeda.com

Investor Relations Contact:
Takashi Okubo
takeda.ir.contact@takeda.com
+81 3 3278 2306

Media Inquiries:
Tsuyoshi Tada (Outside of Japan)
Tsuyoshi.Tada@takeda.com
+1 617 551 2933

Kazumi Kobayashi (Japan)
Kazumi.kobayashi@takeda.com
+81 3 3278 2095

Share this post


Link to post
Share on other sites
Rachel

curious if people have tried this motegrity and is there any success?

Share this post


Link to post
Share on other sites
TexasEddie

Hi, the product description for Motegrity says it is a serotonin-4 receptor agonist. Does that mean it enhances serotonin levels in the GI tract? 

Edited by TexasEddie
Set notification of replies. thanks

Share this post


Link to post
Share on other sites
Jeffrey Roberts

Yes, that's the intention of a 5-HT4 agonist, to increase serotonin, which then increases motility.

Share this post


Link to post
Share on other sites
TexasEddie

Then that is probably why my motility is almost non-existent. My blood serotonin levels were tested recently and my serotonin was deficient.  That makes sense.  I had asked my pharmacist this question previously and he said that he did not know.  I also had contacted the company that makes the product and asked them if a person with low serotonin could take Motegrity and their so called specialist couldn't answer the question. Thank you for your assistance.

Eddie. 

Share this post


Link to post
Share on other sites
Jeffrey Roberts

I am not certain if blood serotonin is the same as the serotonin that is found in the gut. That may be why nobody can give you an answer. There are different types of serotonin. Motegrity affects 5-HT4, but there are other's 5-HT1, 2, 3, etc..

Antidepressants and anti-anxiety meds, etc... affect serotonin found in the brain. I'm not sure if that shows up in blood tests either.

  • Like 1

Share this post


Link to post
Share on other sites
TexasEddie

Thanks again Mr. Roberts. I appreciate all your comments. 

  • Like 1

Share this post


Link to post
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.


×
×
  • Create New...