Ritter Pharmaceuticals Inc. is reeling from the phase III failure of its lead candidate, RP-G28, designed for patients with lactose intolerance. RP-G28 failed to demonstrate statistical significance in its primary endpoint as the top-line data showed it had no or little difference on patients compared to placebo. The data also show RP-G28 missed its secondary endpoints, all of which casts a shadow on the company and its pipeline.

The Los Angeles-based company's stock (NASDAQ:RTTR) opened solidly down and stayed that way Friday, closing at 32 cents, for a loss of 70% per share.

"We are exploring our possible future alternatives," Ritter's chief financial officer, John Beck, told BioWorld. "Ritter will provide further information regarding its efforts if and when appropriate."

Andrew Ritter, the company's founder and president, said he believed the trial to be "well-designed and executed." Once the results are analyzed, he added, the company will assess its future, "which may include alternative strategic options."

Troubles were on the horizon before the data were released. On Aug. 19, the 11-year-old company received a written notice from Nasdaq that it was not in compliance with Nasdaq's listing rule 5550(b)(1), as the stockholders' equity, shown in its second-quarter report, did not satisfy conditions for the alternative market value of listed securities standard for continued listing or the net income standard for continued listing. According to Ritter's SEC form 8-K filing, the notice had no immediate effect on its Nasdaq listing, and the company has until Oct. 3 to submit a plan to regain compliance.

Also, according to its recent SEC form 10-Q, for the six months ending June 30, Ritter had a net loss of approximately $7.5 million and had net cash used in operating activities of approximately $10.4 million. At June 30, it had working capital of approximately $2 million, an accumulated deficit of approximately $77.7 million, and cash and cash equivalents of approximately $4.4 million.

Ritter was investigating the functionality and therapeutic potential that gut microbiome changes may have on treating and/or preventing a variety of conditions, including gastrointestinal diseases, cancer, metabolic and liver diseases. The company said this summer it intended to expand its product pipeline by evaluating RP-G28 in other indications, including orphan indications, as well as developing additional products based on its underlying, microbiome-modulating technology, or in-licensing complementary products to treat those, or other, conditions.

No improvement

The failed multicenter, randomized, placebo-controlled, parallel-group trial of 557 adult patients included quadruple masking of participants, care providers, investigators and outcomes assessors. RP-G28, a galacto-oligosaccharide, which was spray dried as a powder for oral administration, was given to some patients twice daily in doses of 7.5 grams. The placebo, maltodextrin, was given to other patients with the same frequency, administration and dosage.

In the study's primary endpoint, measuring lactose intolerance symptoms at day 61, (30 days post treatment), compared to baseline, patients showed a 3.159 mean reduction compared to a reported 3.420 mean reduction in the placebo group (p=0.106). The lactose intolerance composite score created for the study included abdominal pain, abdominal bloating, abdominal cramping and abdominal gas.

In its missed first secondary endpoint, responders with a meaningful treatment benefit: 36.2% of treatment group compared to 34.1% of placebo group (p=0.284). That secondary endpoint's composite score included the same symptoms as the primary outcome measure.

The remaining secondary endpoints also missed statistical significance, with treatment and placebo generally reporting similar results to each other.

RP-G28 was generally well-tolerated, with placebo and treatment groups reporting similar safety profiles.

Three years ago, Ritter left open the option of two trials for RP-G28.

"We are operating under the assumption that we will be required to do two pivotal phase III trials," Ritter told BioWorld at the time. Ritter, who suffers from lactose intolerance, began his research in middle school and used himself as the first test subject to develop and test a first-generation therapy formulated as a dietary supplement, an effort that led RP-G28's development as the second-generation candidate. (See BioWorld, March 15, 2016.)

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