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KDDF-201210-13 Late phase global clinical development of YKP10811, a drug for functional gastrointestinal disorder(Gastrointestinal Diseases, Chemical) [01.17.2013]

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Development and Market Objectives

SK Biopharmaceuticals has conducted a definitive Phase 2 proof-of-concept study for upper GI motility as well as relief of constipation in patients at the Mayo Clinic. Preliminary data have provided strong suggestions of efficacy throughout gut, particularly gastroprokinetic action in chronic idiopathic constipation (CIC) with distinguishing safety and tolerability. Preparations for a dose-range finding Phase 2b study in CIC are underway. After this trial is completed, our goals are to partner with a large pharmaceutical company for full development and commercialization in the primary care market in the US and with other global or regional partners outside the US for development and commercialization for the gastroenterology market.

Unmet Medical Need & Target Patients

● Unmet medical need
With the withdrawal of Propulsid and Zelnorm from the market for safety reasons, a large unmet need was created for gastroprokinetic agents in IBS-c, CIC, and gastroparesis. In addition, previously marketed agents suffered from a loss of efficacy after the long-term use that is necessitated by the chronic condition. Heretofore, patients have had to rely on over the counter harsh laxatives, bulking agents, and stool softeners for relief. Recently launched drugs in this indication have been so-called secretogogues that increase the water content of the large bowel, but have little effect on the upper gastrointestinal system. Therefore, it is paramount to develop a drug that exhibits broad efficacy on various symptoms throughout the gastrointestinal tract, has fewer adverse effects, and maintains stable efficacy upon long-term administration.


● Target patients
Target patients for YKP10811 are those with CIC and IBS-c . It has been shown that 14% of adults, or 92 million patients are in the major seven markets including the US for CIC, and that a third of patients with irritable bowel syndrome have IBS-c.

 

Status

YKP10811 has a precedented mechanism of action, acting at the serotonin 5-HT4 receptor, with increased selectivity over existing agents and with partial agonist properties that distinguish it from all other competitors in the modality. These properties suggest outstanding efficacy with unsurpassed safety and tolerability as demonstrated by preclinical testing. Early clinical trials have established oral bioavailability, with mild or moderate adverse events, most of a gastrointestinal nature reflecting the gastroprokinetic effect of the drug. The proof-of-concept study confirmed broad gastroprokinetic efficacy in patients suffering with CIC. The proof-of-efficacy study (http://clinicaltrials.gov/, NCT01989234) for clinical efficacy is underway. In addition, tests for long-term toxicity (six months in rats, six and nine months in dogs) and carcinogenicity are underway.

 

Intellectual Property

Composition of Matter Patent:
Parent case filed October 2008
Pending: USA, Korea, Canada, Brazil, EP, Japan, China, Russia, Australia, India, Mexico
 

Competitive Advantages

• Superior efficacy compared to existing drugs; As it shows superior efficacy compared with existing released drugs such as tegaserod or prucalopride in a variety of performance assessment animal models and clinical biomarker study, it is expected to perform well in clinics.
 
Possibility of expansion to other indications
(1) Broad efficacy on general gastrointestinal tract; Since YKP10811 exhibits broad gastroprokinetic action across the upper GI system as well as the lower GI system in animal models and clinical biomarker study, an expansion of its usage is expected into other diseases such as functional dyspepsia or gastroparesis.
(2) Abdominal pain relief; As it reduces pain in a visceral hypersensitivity model, it is expected to alleviate the pain that accompanies IBS-c.
 
Safety
YKP10811 has very low risk of QTc prolongation compared with cisapride, an existing drug with the same mechanism of action, and maintains high selectivity for the target associated with efficacy. In addition, it does not bind to other kinds of serotonin receptors, such at the 5-HT1B or 1D subtypes. Thus, it is expected to have fewer side effects, such as cardiac ischemia, as compared with tegaserod. This safety has been confirmed in preclinical studies and the Phase 1 and Phase IIa clinical trials conducted to date.
 
Maintenance of long-term efficacy
Unlike previous serotonin 5-HT4 agonists, it has been demonstrated that YKP10811 does not lose its effectiveness upon subchronic administration to animals in their pain response to intestinal distention.

Indication

Gastrointestinal Disease

Research Period

Dec. 01, 2012-Feb. 02, 2014

Company

SK Biopharmaceuticals

Developmental Stage

Phase IIa

Additional Information

Contact Information

Contact
Address Company Name: SK biopharmaceuticals
WebSite Homepage: http://www.skbp.com Contact Person: In-Tae Kim, Hae In Shin
E-mail: intae.kim@sk.com, haein.shin@sk.com Contact: 82-42-866-7675, 82-2-2121-5353

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