FDA pre-IND meeting minutes describe steps required for new drug application (NDA) submission
No additional toxicology studies required to initiate Phase 2 trial
EndoLogic will move forward with a 12-week renzapride Phase 2 trial that could be considered one of two pivotal studies
CLIFTON, N.J., Aug. 09, 2017 (GLOBE NEWSWIRE) -- EndoLogic announced that it has received the minutes from the U.S. Food and Drug Administration (FDA) of a pre-IND meeting held to discuss the requirements for an IND submission to initiate a proposed Phase 2 trial and later NDA submission of the prokinetic agent, renzapride, for use in patients with diabetic gastroparesis. The meeting was held on July 25, 2017.
The minutes indicate that:
- No additional toxicology studies would be required to proceed with the Phase 2 trial; all previous toxicology work conducted by Alizyme, the prior sponsor of renzapride, will be accepted;
- The chemistry, manufacturing and controls approach to be executed by Patheon, Inc., to manufacture the renzapride active pharmaceutical ingredient (API) and finished renzapride capsule, is acceptable to the FDA for submission of the IND;
- The Phase 2 trial will be extended to 12 weeks rather than the four weeks as originally proposed; this revision in the study protocol would enable the trial, if successful, to be considered as one of two pivotal trials essential to submit an NDA;
- A thorough QT study, successfully completed and previously submitted to the FDA by Alizyme, will be reviewed by the FDA for adequacy; that study demonstrated no significant QT prolongation at renzapride doses from 4 mg per day (the maximum proposed dose for the Phase 2 trial) to 20 mg per day (a supra-therapeutic dose).
“We had a very positive and constructive meeting with the FDA and we are now finalizing the design of the Phase 2 study,” said Zamir S. Brelvi M.D., Ph.D., co-founder and chief executive officer of EndoLogic. “The meeting outcome clarifies our development path, and both lowers the potential cost of development and potentially shortens our timeline toward an NDA submission compared to our original expectations. We are currently seeking to raise $15 million that will be employed to complete the manufacturing of renzapride and fund the Phase 2 trial.”
Kamal Dutta, M.D. co-founder and president of EndoLogic added, “We anticipate submitting the IND in the fourth quarter of 2017, with dosing of the first patient expected in the second quarter of 2018. Now that the development path is defined, we are looking forward to fully developing renzapride and ultimately bringing it to patients who need it.”
Renzapride, a 5-HT4 agonist and 5HT-3 antagonist, has been studied in more than 5,000 patients including in one Phase 3 trial for the treatment of constipation-dominant irritable bowel syndrome (IBS-C). Renzapride demonstrated a statistically significant benefit in the Phase 3 study in IBS-C. The drug was also well tolerated and showed no evidence of cardiotoxicity. A pilot Phase 2 study in patients with diabetic gastroparesis showed that doses of 0.5 mg, 1.0 mg and 2.0 mg, once-daily, showed significant improvement in gastric emptying in a dose-dependent manner. The company plans to conduct the Phase 2 study to identify the best dose to treat diabetic gastroparesis for the second pivotal trial.
Gastroparesis is a common condition affecting more than 20 million people in the U.S. including five million diabetics. Currently, treatment options are limited with only one drug, metoclopramide (brand name Reglan®), a four times daily oral dopamine D2 receptor antagonist, approved for the treatment of gastroparesis; however, treatment with metoclopramide for more than 12 weeks should be avoided due to the risk of tardive dyskinesia. Renzapride, a twice-daily oral medication, could be a promising option for patients with gastroparesis. Being a prokinetic agent, it also has potential benefit in other indications such as proton pump inhibitor-refractory gastroesophageal reflux disease (GERD) and functional dyspepsia. Both of these conditions combined affect 50 million patients in the U.S.
About EndoLogic
The mission of EndoLogic LLC is to design, develop, and market new products to treat gastrointestinal diseases. The company is developing renzapride, a 5HT-4 agonist and 5HT3 antagonist, for the treatment of diabetic gastroparesis, a poorly-met medical need and for other gastrointestinal indications. The company has also developed a series of medical device products for the removal of colon polyps and foreign bodies. 510(k) applications are being prepared for submission to the U.S. Food and Drug Administration for review. The company’s founders are Dr. Zamir S. Brelvi, a U.S. trained gastroenterologist and academic researcher with a vast experience in endoscopic procedures and device development, and Dr. Kamal Dutta. Dr. Dutta, a pelvic surgeon, who has more than 30 years of experience in research and development of pharmaceutical products and medical devices.
Corporate contact: Zamir S. Brelvi M.D., Ph.D. Chief Executive Officer zbrelvi@endologicusa.com Investor contact: Robert Flamm, Ph.D. Senior vice president The Ruth Group P: 646-536-7017 rflamm@theruthgroup.com
