SAN FRANCISCO–(BUSINESS WIRE)–OrphoMed, Inc., a clinical-stage biopharmaceutical company developing first-in-class dimer therapeutics, today announced positive results from the recent Phase 2 study of ORP-101 for treatment of irritable bowel syndrome with diarrhea (IBS-D). The double-blind, placebo-controlled, 12-week response adaptive randomization study investigated once-daily doses of 100 mg and 50 mg of ORP-101 vs. placebo. The 100 mg dose was more effective than placebo, whereas the 50 mg dose did not achieve statistical separation. Overall, ORP-101 was safe and well tolerated in all patients. Importantly, ORP-101 was also effective and safe in post-cholecystectomy IBS-D patients at the 100 mg dose throughout the treatment period.
The primary efficacy endpoint (composite responder rate) was defined as the proportion of patients who recorded a reduction of 30% or more from baseline in the daily average score for the worst abdominal pain for at least 50% of days assessed and, on same days, a daily average stool consistency score of <5 (on a scale of 1-7, with 1 indicating hard stool and 7 indicating watery diarrhea) over the 12-week treatment period. In the final analysis, of the 320 randomized patients, 20 patients were excluded per protocol from the analysis because they were unable to comply with the study requirements due to COVID-19 lockdowns. The protocol also required investigators to follow up with patients who used loperamide excessively during the trial. These 36 patients were designated as non-responders.
For the primary efficacy endpoint, ORP-101 100 mg was superior to placebo (p=0.008). It was also significantly better than placebo on secondary and exploratory endpoints, including stool consistency, IBS abdominal relief, global symptoms, IBS quality of life, and average weekly abdominal pain, discomfort, and bloating, and fewer episodes of bowel incontinence. On the secondary endpoint of abdominal pain, ORP-101 also showed a strong trend toward efficacy with a treatment difference of 8.5 percentage points.
In IBS-D post-cholecystectomy patients (n=85), the treatment effect was more robust, with an approximately 18 percentage point difference in composite responder rate between ORP-101 100 mg and placebo, p=0.04.
Overall, ORP-101 demonstrated a favorable safety profile. ORP-101 100 mg met its primary endpoint in this Phase 2 study, notably without constipation as an adverse event and without opioid central nervous system effects (euphoria, motor or respiratory effects, drunkenness, etc.). ORP-101 100 mg was safe in patients without gallbladder over the 12-week treatment period, as there was no observed elevation in pancreatic enzymes or sphincter of Oddi spasms.
Study Chairman Anthony Lembo, M.D. stated, “Based on the results of this Phase 2 trial, ORP-101 has the potential to be an effective and safe treatment without evidence of constipation for patients with IBS-D, including those without gallbladders.”
Gary Phillips, M.D., President and Chief Executive Officer of OrphoMed stated, “These favorable Phase 2 data represent a major milestone for ORP-101 and for OrphoMed as an emerging biotech, as they provide clinical proof of concept and dose for further investigation in the Phase 3 study. Furthermore, the clinical results for ORP-101 validate the dimer therapeutics approach on which OrphoMed was founded. I am looking forward to moving ORP-101 into later stages of development.”
About the ORP-101 Phase 2 Trial
The trial was a multi-center, double-blind, placebo-controlled, response-adaptive randomization study to evaluate the safety and efficacy of ORP-101 in 320 patients with IBS-D. Study participants were randomized to receive one of two different doses of ORP-101 tablets or placebo for 12 weeks. The primary endpoint was percentage of patients who were composite responders, based on improvements from baseline in daily worst abdominal pain and daily stool consistency scores. Secondary endpoints included percentage of participants who were responders in the following assessments: daily worst abdominal pain, daily stool consistency, IBS global symptom, IBS adequate relief, modified composite response, daily abdominal discomfort, daily abdominal bloating, number of bowel movements per day, and number of bowel incontinence-free days.
For the final statistical analysis, which occurred approximately 14 weeks after the last patient was randomized, a one-sided p-value was calculated for the two-sample proportion test comparing patients in the optimal active arm versus placebo.
For more information about the study, please see www.orphomed.com.
ORP-101 is a new chemical entity designed to confer peripheral partial μ agonist and full κ receptor antagonist activity, enabling treatment of both IBS-D symptoms of dysmotility and pain without the risk of sphincter of Oddi spasm or pancreatitis.
- Successfully completed Phase 1 clinical trials and was granted FDA Fast Track designation in 2018. Regulatory path to NDA has been agreed with the FDA
- Phase 2 clinical trial successfully completed in November 2021
- Shown in preclinical studies to not cross the blood-brain barrier and therefore likely non-addictive
- Avoids sphincter of Oddi dysfunction by relaxing it
- Metabolically stable: drug-drug interaction risk is low
About OrphoMed, Inc.
OrphoMed is a clinical-stage biopharmaceutical company focused on the development of innovative and de-risked first-in-class dimer therapeutics. Leveraging its proprietary dimer platform technology engineered by founder Nikhilesh Singh, Ph.D., OrphoMed is advancing ORP-101 and a pipeline of additional dimer conjugates. To date, OrphoMed has completed a $43 million Series A financing with New Enterprise Associates, Takeda Ventures, Pappas Capital and Relativity Healthcare. OrphoMed is currently evaluating all strategic options, including advancing the compound through Phase 3 and NDA submission. For more information, please visit www.orphomed.com.
This press release contains “forward-looking statements,” which reflect our current views and expectations with respect to future outcomes or events. When used in this press release, the words “could,” “believe,” “anticipate,” “intend,” “estimate,” “expect,” “project” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain such identifying words. Because these statements are based on current estimates and assumptions, they are inherently subject to risks that could cause the actual outcomes to differ materially from what we currently expect. These forward-looking statements are subject to numerous risks and uncertainties, including, among others, the facts that we are substantially dependent on our ability to successfully develop and commercialize our products; the commercial adoption of our products and any other product candidates we develop will depend on the degree of their market acceptance; we have only limited assets and will need to raise additional capital before we can expect to generate revenue or become profitable; and we have never generated any revenue and may never be profitable. Forward-looking statements in this presentation apply only as of the date made, and we undertake no obligation to update or revise any forward-looking statements to reflect subsequent events or circumstances.