- The plecanatide new drug application (NDA) in chronic idiopathic constipation (CIC) is currently under review by the Food and Drug Administration (FDA) and the Prescription Drug User Fee Act (PDUFA) target action date is January 29, 2017. Plecanatide is the first investigational therapy designed to replicate the activity of uroguanylin, a naturally occurring human GI peptide, by working locally primarily in the proximal small intestine to stimulate digestive fluid movement and support regular bowel function.
- The late-cycle review meeting with the FDA was completed and no significant issues were identified. The FDA previously informed us that there are no plans at this time for an advisory committee meeting in connection with the review of the plecanatide NDA in CIC. The plecanatide NDA in CIC is supported by two double-blind, placebo-controlled phase 3 trials and one long-term open-label safety study. Over 3,500 patients have been exposed to plecanatide in the CIC clinical development program.
- Two posters were presented on the plecanatide CIC clinical data at the American College of Gastroenterology (ACG) annual scientific meeting in October 2016.
- Safety and Tolerability of Plecanatide in Patients with Chronic Idiopathic Constipation: Long-term Evidence from an Open-Label Study
- Data presented from the long-term open-label safety study showed plecanatide was associated with low adverse events and low discontinuation rates in patients with CIC who received plecanatide (3 mg or 6 mg) once-daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%). The remainder of adverse events occurred in less than 2% of patients treated with plecanatide. Adverse events leading to discontinuation occurred in 5.3% of patients treated with plecanatide, with discontinuation due to diarrhea occurring in 3.1% of patients. In addition, this study asked patients about level of treatment satisfaction and desire to continue treatment. The median score for treatment satisfaction was 4.0 (4=quite satisfied) and for continuation of treatment was 4.0 (4=quite likely).
- Efficacy and Safety of Plecanatide in the Treatment of Chronic Idiopathic Constipation (CIC): Pooled Results from Two Phase 3 Studies
- Pooled results from two previously reported double-blind placebo-controlled phase 3 CIC trials confirmed patients treated with plecanatide showed a significantly greater response rate of durable overall complete spontaneous bowel movements compared to placebo (20.5% in 3 mg and 19.8% in 6mg dose groups compared to 11.5% in placebo; p<0.001 for both doses). This is the primary endpoint defined by the FDA for regulatory approval in CIC. This integrated analysis also showed consistent safety data with adverse event rates similar across plecanatide-treatment groups and placebo (30.6% in 3 mg and 31.1% in 6 mg dose groups compared to 28.7% in placebo). Diarrhea was the most common adverse event (4.6% in 3 mg and 5.1% in 6 mg compared to 1.3% in placebo). Discontinuation rates were low across all treatment groups (4.1% in 3.0 mg and 4.5% in 6.0 mg dose groups compared to 2.2% in placebo).
- Patient enrollment has been completed in the two double-blind, placebo-controlled phase 3 clinical trials with plecanatide in IBS-C patients. Top-line data in both trials are expected by the end of this year. The primary endpoint in both trials is the percentage of patients who are Overall Responders during the 12-week treatment period. An Overall Responder, as defined by the FDA, is a patient who is a weekly responder (i.e. meets both a 30% abdominal pain intensity reduction and stool frequency increase criteria in the same week) for at least 6 of the 12 treatment weeks. Plecanatide previously met this endpoint in a phase 2b trial with 424 IBS-C patients that was completed in 2014.
- The IBS-C pre-NDA meeting with the FDA was completed in September 2016. Pending approval of plecanatide in the CIC indication, we plan to file a New Drug Application Supplement with Clinical Data (sNDA) for plecanatide in IBS-C in the first quarter of 2017 and expect a 10-month review period from submission.
Product ReadinessKey Highlights
- Met all technical operations timelines to-date and remain on-track to complete all activities by the anticipated launch of plecanatide in early 2017.
- Established a robust supply chain and actively producing commercial product.
- Continuing to build trade and sample stock for launch in early 2017.
- Implemented 3PL distribution network.
- Established strong Quality Management Systems.
- Generated substantial customer insights through qualitative and quantitative market research that will include more than 2,700 HCPs and more than 5,000 patients/consumers by the end of 2016.
- Conducted multiple productive advisory boards with national and regional GI Key Opinion Leaders and payers.
- Finalized plecanatide brand vision, brand positioning, value proposition, core marketing strategies and launch tactics; our message platform and a creative campaign will be completed and ready by year-end.
- Initiated pre-launch multimedia and digital campaigns to drive company awareness and disease education, focusing on current unmet medical needs of patients with CIC.
- Developed a compliant, value maximizing, and cost-effective promotional mix to reach the broadest universe of prescribers.
- Market Access team has conducted meetings with all key commercial and public payers, representing approximately 230 million covered lives in the U.S.
- National and regional market access teams have been active and in the field introducing Synergy Pharmaceuticals to payers since January 2016.
- Medical education efforts initiated in March 2016 and included strong corporate presence and key data presentations at Digestive Disease Week and ACG.
- Hired regional sales leaders averaging more than 10 years of GI experience who are driving important pre-launch initiatives and who will support an effective hybrid sales infrastructure that will be deployed at launch.
- Initiated a partnership with Publicis Touchpoint Solutions, Inc. to implement a cost-effective, flexible hybrid sales force, leveraging highly experienced sales representatives who will be fully dedicated to supporting the launch and adoption of plecanatide.
- Established a focused and efficient sales force strategy, combined with a comprehensive multi-channel approach, to reach the key prescribers and influencers at launch.
- Implemented all critical IT and compliance systems.
- As of September 30, 2016, we had approximately $109.1 million of cash and cash equivalents on hand as compared to approximately $111.8 million cash and cash equivalents and available for sale securities as of December 31, 2015.
- Net cash used in operating activities was $92.0 million in the nine months ended September 30, 2016, as compared to $70.7 million in the nine months ended September 30, 2015.
- Research and development expenses in the third quarter of 2016 were approximately $24.6 million, as compared to $20.4 million in the third quarter of 2015. These increased expenses were primarily a result of higher spending on IBS-C studies, additional technical operations and medical affairs operating expenses as well as drug product related costs for our commercial launch in the first quarter of 2017.
- Selling, general and administrative expenses were approximately $13.9 million in the third quarter of 2016, as compared to approximately $2.7 million in the third quarter of 2015. These increased expenses primarily reflect commercial preparedness and planning expenses to support an anticipated launch of plecanatide during the first quarter of 2017.
- On May 6, 2016, we closed on a registered direct offering of approximately 30 million shares of our common stock with gross proceeds of approximately $89.8 million.
- As of September 30, 2016, the principal balance on our 7.50% Convertible Senior Notes ("Notes") due 2019 was $79.2 million as compared to $159.0 million at December 31, 2015.
- We had 179.8 million and 113.7 million common shares issued and outstanding at September 30, 2016 and December 31, 2015, respectively, which reflects primarily an increase in the issuance of shares from the first quarter conversions of the Notes and the common stock offering noted above.
- Net loss in the third quarter of 2016 was $40.2 million, as compared to a net loss of $26.0 million incurred in the third quarter of 2015.
|Synergy Pharmaceutical Inc. Condensed Consolidated Balance Sheets|
|($ in thousands)||September 30, 2016 (unaudited)||December 31, 2015|
|Cash, cash equivalents and available for sale securities||$||109,090||$||111,750|
|Prepaid expenses and other current assets||1,744||3,305|
|Total Current assets||110,834||115,055|
|Liabilities and Stockholders' Equity/(Deficit)|
|Total Current Liabilities||$||23,517||$||19,579|
|Senior Convertible Notes, net||76,070||151,241|
|Derivative financial instruments - warrants||171||322|
|Total Stockholders' Equity/(Deficit)||12,054||(55,213||)|
|Total Liabilities and Stockholders' Equity/(Deficit)||$||111,812||$||115,929|
|Condensed Consolidated Statement of Operations ($ in thousands except share and per share data) (unaudited)|
|Three Months Ended September 30,||Three Months Ended September 30,||Nine Months Ended September 30,||Nine Months Ended September 30,|
|Costs and Expenses:|
|Research and development||24,610||20,424||72,396||58,147|
|Selling, general and administrative||13,872||2,728||30,497||14,727|
|Loss from Operations||(38,482||)||(23,152||)||(102,893||)||(72,874||)|
|Interest and investment expense, net||(1,674||)||(4,291||)||(10,383||)||(13,815||)|
|Debt conversion expense||—||—||(25,615||)||—|
|Change in fair value of financial instruments||(87||)||1,446||151||(364||)|
|Total Other Loss||(1,761||)||(2,845||)||(35,847||)||(14,179||)|
|Net Loss per Common Share, Basic and Diluted||$||(0.22||)||$||(0.23||)||$||(0.89||)||$||(0.85||)|
|Weighted Average Common Shares Outstanding||179,786,580||111,328,339||155,410,353||102,838,814|