Prucalopride (SHP555) Update for Global Investors

Transcription

1 Prucalopride (SHP555) Update for Global Investors March 7, 2018

2 Prucalopride - Introduction U.S. FDA Accepts New Drug Application for Prucalopride (SHP555) for Chronic Idiopathic Constipation (CIC) Prucalopride is an investigational product for the treatment of chronic idiopathic constipation in adults in the U.S. The product is investigational. The U.S. FDA accepted submission of Shire s NDA and the PDUFA date is on or around December 21, 2018 Shire does not know when or if FDA will approve prucalopride Shire cannot predict the content of the labeling for prucalopride in the event of FDA approval This presentation updates investors on Shire s current development plan for prucalopride 2

3 Prucalopride - Summary U.S. FDA Accepts New Drug Application for Prucalopride (SHP555) for Chronic Idiopathic Constipation (CIC) Reinforces Shire s long-standing heritage in gastrointestinal (GI) conditions and deep customer relationships and in-house capabilities Strong addition to GI franchise, which includes LIALDA, GATTEX and provides bridge to pipeline assets such as SHP621 and SHP647 If approved, prucalopride will be the only readily available 5-HT4 agonist 1 in the U.S. to treat CIC in adults CIC affects an estimated 35 million people in the U.S. 2,3* Many patients are dissatisfied with or do not respond to current therapies 4 Efficacy and safety evaluated in five main Phase 3 and one Phase 4 double-blind, placebo-controlled clinical trials 5,6 NDA submission includes real-world evidence from an observational, pharmacoepidemiology cardiovascular safety study 7 *This represents ~14% of the U.S. population as of July 1, 2016 Census Bureau Data. 1. Briejer MR et al. Eur J Pharmacol. 2001;423(1): Suares NC, Ford AC. Prevalence of, and Risk Factors for, Chronic Idiopathic Constipation in the Community: Systematic Review and Meta-analysis. The American Journal of Gastroenterology. 2011;106: US Census Data. Quick Facts. Available at: /. 4. Johanson JF & Kralstein J Aliment Pharmacol Ther 2007;25: Clinical Trials and Related Publications (Prucalopride). 6. Annex H1 Resolor 7. SPD : Cohort Study of the Relative Incidence of Major Cardiovascular Events Among Patients Initiating Prucalopride Versus a Matched Comparator Cohort. Protocol. 3

4 Prucalopride Overview Mode of action Clinical experience A serotonin type 4 (5-HT4) receptor agonist 1 A gastrointestinal prokinetic agent thought to stimulate colonic peristalsis, increasing bowel motility 1 If approved by FDA*, it would be the only readily available gastrointestinal prokinetic drug available for adults with chronic idiopathic constipation in the U.S. Approved in EU and several other International markets with cumulative patient exposure of approximately 283k person years of treatment 2 Studied in more than 90 clinical trials worldwide over the last 20 years, including six main randomized, controlled clinical trials 3 Timing PDUFA action date of December 21, 2018 with FDA noting that timelines are flexible and subject to change based on workload and identification of potential review issues Patents have already expired; 5 years NCE exclusivity from U.S. launch 1. Wong BS, Manabe N, Camilleri M. Role of prucalopride, a serotonin (5-HT4) receptor agonist, for the treatment of chronic constipation. Clinical and Experimental Gastroenterology. 2010;3: PSUR for Reporting Period: 15 Oct 2016 to 14 Oct 2017: Cumulative and Interval Exposure from Marketing Experience (section 5 of the PSUR). 3. Clinical Trials and Related Publications (Prucalopride). * Shire does not yet know what the final labeling will be for prucalopride, if approved, or if there will be post-marketing requirements or commitments. 4

5 U.S. CIC market and unmet need Disease A common and often debilitating medical problem, with a demonstrated impact on quality of life, and associated with a substantial economic burden 1 There are many causes, and one of the possible underlying problems is an impairment or dysfunction of the gut s ability to move, by contracting and releasing, naturally. 2 U.S. market 35M patients in the U.S. with CIC 2,3* Published population based surveys indicate ~25 40 % of patients were actively seeking treatment with an HCP for CIC 1,4 The value of the Novel Rx constipation market in US is ~$1.7billion (IMS Gross revenue), and growing strongly >20% (2017 vs 2016) 5 Unmet need Many patients are dissatisfied with or do not respond to current therapies 1 Current treatment consists of Rx therapies and OTC laxatives Prucalopride, a serotonin type 4 (5-HT4) receptor agonist, is a gastrointestinal prokinetic agent that stimulates colonic peristalsis, increasing bowel motility 6 and should address an unmet need in adults suffering from CIC CIC is a commonly-occurring condition that affects nearly one in eight people in the United States. Many patients use over-the-counter and prescription medicines, including laxatives, but continue to have constipation symptoms. William D. Chey, MD, Professor of Gastroenterology & Nutrition Sciences, Director of the GI Nutrition & Behavioral Wellness Program, University of Michigan Health System, Ann Arbor. * This represents ~14% of the U.S. population as of July 1, 2016 Census Bureau Data. 1. Johanson JF & Kralstein J Aliment Pharmacol Ther 2007;25: Suares NC, Ford AC. Prevalence of, and Risk Factors for, Chronic Idiopathic Constipation in the Community: Systematic Review and Meta-analysis. The American Journal of Gastroenterology. 2011;106: US Census Data. Quick Facts. Available at: /. 4. Heidelbaugh et al. Am J Gastroenterol 2015; 110: IMS Data on file. 6. Wong BS, Manabe N, Camilleri M. Role of prucalopride, a serotonin (5-HT4) receptor agonist, for the treatment of chronic constipation. Clinical and Experimental Gastroenterology. 2010;3:

6 Prucalopride targets 5-HT4 receptors to increase motility COLON Thought to stimulate 5-HT 4 receptors on intrinsic sensory neurons 1 3 Triggers peristaltic reflex and colonic mass movement 3 RECTUM 1. Briejer MR et al. Eur J Pharmacol. 2001;423(1): Grider JR et al. Gastroenterology. 1998;115(2): Prins NH et al. Br J Pharmacol. 2000;131(5):

7 Key efficacy results 1 Impact on bowel function Integrated analysis of over 2000 patients from four continents demonstrated prucalopride was efficacious in the treatment of individuals with CIC Normalization of bowel movements (average of 3 SCBMs per week over 12 weeks) in 27.8% of adults versus 13.2% on placebo (P<0.001) Clinically meaningful improvement in bowel function (average increase of 1 SCBMs per week over 12 weeks) in 47.0% of adults on prucalopride versus 29.9% on placebo (P<0.001) Additional endpoints Significant reduction in the time to first SCBM Significant reductions in rescue medication for both mean number of tablets and mean days of use with prucalopride (P<0.001) Note: SCBMs = spontaneous complete bowel movements); PAC-SYM = patient assessment of constipation symptoms questionnaire; PAC-QOL: patient assessment of constipation quality of life questionnaire. 1. Camilleri M et al. Dig Dis Sci. 2016;61(8):

8 Key safety results 1 Overall, 806 patients (63.3%) in the prucalopride group and 682 patients (53.3%) in the placebo group experienced 1 TEAE The majority of TEAEs experienced by patients in both treatment groups were mild or moderate in severity Most common adverse events were similar in both men and women and included gastrointestinal disorders (nausea, diarrhea, and abdominal pain) and headache Fewer men than women experienced TEAEs (prucalopride group, 47.2 versus 68.5%; placebo group, 38.5 versus 58.0%, respectively) The proportion of patients who experienced any adverse cardiovascular events was low and comparable between groups (1.8% for placebo versus 2.0% for prucalopride) TEAEs led to permanent discontinuation for 3.4% of subjects in the placebo group and 5.2% of subjects in the prucalopride group 1. Camilleri M et al. Dig Dis Sci. 2016;61(8):

9 Supporting gastroenterologists to manage patients with different GI conditions SHP555* US Lialda (Mesalamine) Pentasa/US only - Shire (Mesalamine) SHP647* Gattex (teduglutide [rdna origin]) SHP621* 5-HT 4 receptor agonist Anti MAdCAM GLP-2 analog Topical steroid Chronic Idiopathic Constipation (CIC) Ulcerative Colitis (UC) (mild to moderate) Inflammatory Bowel Disease (IBD) (moderate to severe) Short Bowel Syndrome (SBS) Eosinophilic Esophagitis (EOE) 20-30% IBD of patients undergo surgery Specialty GI Rare GI * Investigational compound in the US and has not been approved for use by the US Food and Drug Administration. 9

10 Safe Harbor Statement Under The Private Securities Litigation Reform Act Of 1995 Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, 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 conducts its own manufacturing operations for certain of its products and is reliant on third party contract manufacturers to manufacture other products and to provide goods and services. Some of Shire s products or ingredients are only available from a single approved source for manufacture. 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; certain of Shire s therapies involve lengthy and complex processes, which 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; Shire s products and product candidates face substantial competition in the product markets in which it operates, including 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 the Company s revenues, financial condition or results of operations; inability to successfully compete for highly qualified personnel from other companies and organizations; failure to achieve the strategic objectives, including expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all with respect to Shire s acquisitions, including NPS Pharmaceuticals Inc., Dyax Corp. or Baxalta Incorporated 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, as well as changes in foreign currency exchange rates and interest rates, that adversely impact the availability and cost of credit and customer purchasing and payment patterns, including the collectability of customer accounts receivable; failure of a marketed product to work effectively or if such a product is the cause of adverse side effects could result in damage to Shire s reputation, the withdrawal of the product and legal action against Shire; investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire s activities in the highly regulated markets in which it operates may result in significant legal costs and the payment of substantial compensation or fines; 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 incurred substantial additional indebtedness to finance the Baxalta acquisition, which may decrease its business flexibility and increase borrowing costs; 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 ITEM 1A: Risk Factors, and in 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. 10