On January 4, 2017, Evoke Pharma, Inc. (the Company) a
specialty pharmaceutical company focused on treatments for gastrointestinal (GI) diseases, provided additional data from the Phase 3 trial of Gimoti, its nasal delivery of metoclopramide for the relief of symptoms associated with acute
and recurrent diabetic gastroparesis in adult women. Although the Phase 3 trial failed to reach its primary endpoint, data also demonstrated that patients with moderate to severe symptoms, which included 105 of the 205 patients (51%) enrolled in the
study, responded statistically significantly better when treated with Gimoti than those treated with placebo at multiple time points in the
Intent-to-Treat
(ITT) and Per Protocol populations (Table 1). There were also clinically and statistically significant improvements in nausea and abdominal pain, which are two of the more severe and debilitating symptoms of gastroparesis (Table 2).
These results in patients with moderate to severe symptoms are consistent with the U.S. Food and Drug Administration (FDA)
guidance on the clinical evaluation of drugs for the treatment of gastroparesis issued in July 2015 (
Gastroparesis: Clinical Evaluation of Drugs for Treatment, Draft Guidance
). This guidance represents the FDAs current thinking on the
evaluation of treatments for gastroparesis and states that trials should enroll patients with higher symptom severity in order to optimize the ability to demonstrate a treatment effect. At the time this guidance was issued, the Companys Phase
3 study, designed to include patients with a range of symptom severity, had been actively enrolling for more than a year. The overall efficacy results were not significant, due in large part to the milder patients who responded to placebo.
Importantly, the efficacy of Gimoti was demonstrated in the subset of patients described in the guidance, i.e., those who entered the study with higher symptom severity.
Phase 3 safety data revealed no significant adverse effects and were consistent with favorable results from previous Gimoti studies. In
particular, there were no adverse events of special interest, such as the central nervous system (CNS) effects observed with oral and parenteral metoclopramide (Table 3). There have been no reports of tardive dyskinesia among the 1,311
exposed healthy volunteers and patients over the clinical development program.
The trial was a U.S. multicenter, randomized,
double-blind, placebo-controlled, parallel group study of the efficacy and safety of Gimoti compared to placebo in adult female subjects with symptomatic diabetic gastroparesis and delayed gastric emptying. Eligible patients were randomized 1:1
between Gimoti or placebo administered as a single nasal spray four times daily; 30 minutes before meals and at bedtime for a total of four weeks. The primary endpoint was the change in the total symptom score from baseline to week four and was not
statistically significant in the ITT group (N=205, p = 0.881). Safety and additional efficacy results are summarized in the tables below.
Table 1:
|
Phase 3 Estimated Mean Change from Baseline in Mean Daily GSA Total Scores: Moderate to Severe Study Populations
|
|
|
|
|
|
|
|
|
|
Population
|
|
Time
Period
|
|
Placebo
1
|
|
Gimoti
1
|
|
p
-value
2
|
Intent-to-Treat
|
|
Week 1
Week 2
Week 3
Week 4
|
|
(N = 53)
-0.387
-0.614
-0.749
-0.856
|
|
(N = 52)
-0.588
-0.950
-1.096
-1.220
|
|
0.036
0.025
0.039
0.085*
|
|
|
|
|
|
Per Protocol
|
|
Week 1
Week 2
Week 3
Week 4
|
|
(N = 40)
-0.362
-0.625
-0.714
-0.841
|
|
(N = 38)
-0.623
-1.040
-1.286
-1.373
|
|
0.019
0.015
0.003
0.014
|
Table 2:
|
Mean Change from Baseline in Mean Daily Nausea and Upper Abdominal Pain Score in
Intent-to-Treat
Population with Moderate to Severe
Symptoms
|
|
|
|
|
|
|
|
|
|
Symptom
|
|
Time
Period
|
|
Placebo
1
(N = 53)
|
|
Gimoti
1
(N = 52)
|
|
p
-value
2
|
Nausea
|
|
Week 1
|
|
-0.370
|
|
-0.859
|
|
0.001
|
|
Week 2
|
|
-0.696
|
|
-1.149
|
|
0.032*
|
|
Week 3
|
|
-0.818
|
|
-1.242
|
|
0.043
|
|
Week 4
|
|
-0.905
|
|
-1.404
|
|
0.027
|
|
|
|
|
|
Upper
Abdominal Pain
|
|
Week 1
|
|
-0.394
|
|
-0.641
|
|
0.025
|
|
Week 2
|
|
-0.554
|
|
-0.990
|
|
0.016
|
|
Week 3
|
|
-0.690
|
|
-1.194
|
|
0.008
|
|
Week 4
|
|
-0.791
|
|
-1.218
|
|
0.047
|
2
|
p
-value is obtained from an ANCOVA model with fixed effect for treatment group and the baselinevalue as a covariate. If the normality assumption was not met,
the
p
-value was obtained from a rankANCOVA test and denoted with an *.
|
Table 3:
|
Selected Treatment-Emergent Adverse Events Reported by More than 2 Subjects in Any Treatment Group
|
|
|
|
|
|
Adverse Event
|
|
Placebo
(N = 103)
|
|
Gimoti
(N = 102)
|
Headache
|
|
7 (7%)
|
|
5 (5%)
|
Nasal discomfort
|
|
4 (4%)
|
|
1 (1%)
|
Epistaxis
|
|
2 (2%)
|
|
1 (1%)
|
Fatigue
|
|
1 (1%)
|
|
2 (2%)
|
Forward-Looking Statements.
The Company cautions you that statements included in this Current Report on Form
8-K
that are not a
description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as may, will, should, , or expect, plan,
anticipate, could, intend, target, project, contemplates, believes, estimates, predicts, potential or continue or the
negatives of these terms or other similar expressions. These statements are based on the companys current beliefs and expectations. These forward-looking statements include statements regarding: the potential for Gimoti to have a positive
impact on the lives of the patients who use it. The inclusion of forward-looking statements should not be regarded as a representation by the Company that any of its plans will be achieved. Actual results may differ from those set forth in this
press release due to the risks and uncertainties inherent in the Companys business, including, without limitation: the data reported only includes a portion of the patients in the Phase 3 clinical trial of Gimoti and that the Phase 3 trial
failed to reach its primary endpoint; risks associated with successfully commencing and receiving favorable results from the planned pharmacokinetic trial; later developments with the FDA that may be inconsistent with the already completed
pre-new
drug application (NDA) meetings, including that the FDA will not accept selected data from our Phase 3 clinical trial; the FDA may change its recommendations regarding evaluation of drugs for the
treatment of gastroparesis; the inherent risks of clinical development of Gimoti; the Company is entirely dependent on the success of Gimoti, and the Company cannot be certain that it will be able to submit an NDA for Gimoti or obtain regulatory
approval for or successfully commercialize Gimoti; risks associated with manufacturing new formulations of Gimoti for use in the pharmacokinetic (PK) trial; the Companys dependence on third parties for the manufacture of Gimoti as
well as the conduct of the PK trial; the Company may require additional funding to complete the PK trial and submit the NDA, and will require substantial additional funding to
commercialize Gimoti, and may be unable to raise capital when needed, including to fund ongoing operations; the Company may not be able to successfully commercialize Gimoti, if approved, as a
result of risks associated with market acceptance, coverage and reimbursement and competing products; and other risks detailed in the periodic reports the Company files with the Securities and Exchange Commission. You are cautioned not to place
undue reliance on these forward-looking statements, which speak only as of the date hereof, and the Company undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking
statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.