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Alcobra Announces Presentation of New Data From Phase III Adult ADHD Study at AACAP Annual Meeting

SAN DIEGO, Oct. 23, 2014 (GLOBE NEWSWIRE) -- Alcobra Ltd. (Nasdaq:ADHD), an emerging pharmaceutical company focused on the development of new medications to help patients with cognitive disorders, including Attention Deficit Hyperactivity Disorder (ADHD) and Fragile X Syndrome, announced the presentation of new data from a Phase III study of Metadoxine Extended Release (MDX) in adults with ADHD at the 61st annual meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).

The data presented at AACAP include new findings on secondary endpoints, including the Clinical Global Impression – Severity (CGI-S) scale, the Clinical Global Impression – Improvement (CGI-I) scale, the Adult ADHD Self-Report (ASRS-Self) scale, ASRS-Self subscales, and safety findings. Updated pre-specified and post-hoc analyses on the study's primary measure were also presented.

Intent To Treat (ITT) Analyses

  • Alcobra previously announced that on the ITT population (n=297), a non-significant favorable trend (p=0.14 in the final report) was obtained on the primary measure of the Conner's Adult ADHD Rating Scale (CAARS-Inv).
  • While a complete ITT analysis by ADHD subtypes is still ongoing and was not presented at AACAP, the magnitude of symptom improvement appears to be similar in all subtypes, and the Predominantly-Inattentive ADHD (PI-ADHD) subtype alone did not produce a statistically significant outcome.
  • New analyses presented at AACAP on the ITT population yielded positive trends or statistically significant findings in favor of MDX compared to Placebo on multiple secondary endpoints analyzed to date, including the CGI-S (p=0.057), CGI-I (p=0.04), ASRS-Self (p=0.12), and the ASRS-Self Inattentive Subscale (p=0.12). MDX did not show a similar advantage on other ASRS-Self Subscales.

Safety and Tolerability Analyses

  • MDX was well tolerated in the study, demonstrating a safety profile with side effects similar to placebo.
  • There were no drug-related serious adverse events reported.
  • There was a low rate of discontinuation in the trial; 15.8% of subjects in the MDX group and 18.2% of subjects in the placebo group discontinued from the study.
  • The most common adverse events seen in the study were headache (15.1% in MDX group vs. 12.3% in placebo group), nausea (8.6% vs. 6.2%), and fatigue (7.2% vs. 8.2%).
  • New data presented at AACAP showed no clinically significant differences between MDX and placebo in blood pressure, pulse, heart rate, weight, EKG values, laboratory values, neurological exams, or physical examinations.

"We are encouraged by these supportive efficacy and safety analyses and plan to use these findings, along with consultation with FDA on the entire data set, to design our second Phase III study of MDX in adults and the Phase III program in pediatric patients," said Dr. Yaron Daniely, Alcobra's President and Chief Executive Officer. "The reduction in ADHD symptoms seen in the MDX group is consistent with our previous clinical trial outcomes, and is clearly hampered by an unusually large and variable placebo response. A variety of pre-specified and post-hoc analyses were done to better understand the effects of MDX and the impact of placebo variability on the findings."

Additional Pre-Specified Analyses

  • A new pre-specified analysis presented at AACAP identified and omitted patients from the ITT population that were found to have an outcome that was ≥3 Standard Deviations away from the average response of the respective treatment group. The analysis, which was conducted on the entire ITT population, identified only 2 patients, both from the placebo treatment group.
  • Importantly, this analysis is different from the post-hoc modified ITT analysis which the company reported on previously as part of the top-line release. The previous analysis excluded 4 patients from the ITT after identifying extreme placebo responses using a combination of statistical and clinical justifications, as described previously.
  • This new pre-specified analysis of any significant outlier (n=295) favored MDX over Placebo on the primary measure (CAARS-Inv) (p=0.06), on the ASRS-Self (p=0.04), and on the ASRS-Self Inattentive Subscale (p=0.05).

Post-hoc Analyses

  • Alcobra previously reported that in a post-hoc modified ITT analysis excluding 4 subjects with extreme placebo responses (based on a comparison to their own treatment group as well as published data on placebo responses in other ADHD clinical trials), MDX showed greater improvement compared to Placebo (p < 0.03).
  • A new post-hoc analysis presented at AACAP evaluated the outcome of exclusion of entry criteria violators (i.e., patients who failed to meet major inclusion/exclusion criteria). This analysis is based on the ICH E9 guideline, "Statistical Principles for Clinical Trials." The analysis, performed by a blinded expert, identified 8 patients (5 from the placebo group and 3 from the MDX group) who were excluded from the ITT analysis for a cohort of 289 subjects.
  • This post-hoc analysis (n=289) demonstrated a trend in favor of MDX over Placebo on the primary measure (CAARS-Inv) (p=0.09), the ASRS-Self (p=0.09), and the ASRS-Self Inattentive Subscale (p=0.09).
  • Another post-hoc analysis presented at AACAP combined the two modifications to the ITT population described above: the 2 subjects excluded based on the pre-specified analysis and the 8 subjects excluded based on the post-hoc entry criteria violation analysis. After combining the two analyses (n=287), MDX demonstrated an advantage over Placebo on CAARS-INV (p=0.04), ASRS-Self (p=0.04) and the ASRS-Self Inattentive Subscale (p=0.04).

"The efficacy signal along with the safety and tolerability profile observed with MDX to date, support the continued development of MDX and its potential as an important addition to available therapies for ADHD," said Dr. Jonathan Rubin, Chief Medical Officer of Alcobra. "It will be important to design the next Phase III study of MDX to better address the high placebo response and large variability observed in this trial. We are confident that we can put such measures into place."

A link to the full AACAP slide deck is available at

http://www.alcobra-pharma.com/secfiling.cfm?filingID=1144204-14-62339&CIK=1566049

Posters with additional MDX data being presented at AACAP will also be made available on the company's website at the conclusion of the conference. Further analyses from this study, including ADHD subtype analyses and evaluation of additional secondary efficacy endpoints, are ongoing.

About MDX

MDX (Metadoxine Extended Release (MG01CI)) is a proprietary investigational new drug candidate being developed by Alcobra for the potential treatment of Attention Deficit Hyperactivity Disorder (ADHD) and Fragile X Syndrome. MDX is not a stimulant and acts as a monoamine-independent modulator of GABA (gamma-aminobutyric acid). This novel mechanism of action does not directly affect dopamine or norepinephrine. In studies to date, metadoxine has shown no potential for abuse or addiction. MDX is currently in Phase III development for adults with ADHD. Additional studies of MDX in adolescents with ADHD and in adolescents and adults with Fragile X Syndrome are currently underway and are actively enrolling patients.

About Attention Deficit Hyperactivity Disorder (ADHD)

Attention Deficit Hyperactivity Disorder (ADHD) is a common and impairing neuropsychiatric condition. Once believed to only affect children, ADHD is now known to persist into adolescence and adulthood in a sizeable number of cases. Key symptoms of ADHD include inattention, hyperactivity and impulsivity.

According to the Centers for Disease Control and Prevention, about 9% of children in the U.S. meet criteria for ADHD with similar numbers reported in other countries. Although boys are more commonly diagnosed, ADHD is also common in girls who often go undiagnosed. Approximately 4-5% of adults worldwide are affected with ADHD, yet most adults with ADHD remain undiagnosed and untreated. There is no known cause of ADHD, however studies suggest that genetics may play a role.

About Alcobra Ltd.

Alcobra Ltd. is an emerging pharmaceutical company primarily focused on the development and commercialization of a proprietary drug candidate, MDX, to treat cognitive disorders including Attention Deficit Hyperactivity Disorder (ADHD) and Fragile X Syndrome. MDX has completed multiple Phase II studies in adults with ADHD and has completed a Phase III study in adults with ADHD. The company is conducting separate Phase IIb trials in pediatric ADHD and Fragile X Syndrome. The company was founded in 2008 and is headquartered in Tel Aviv, Israel. For more information please visit the Company's website, www.alcobra-pharma.com, the content of which is not incorporated herein by reference.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 and other Federal securities laws. Because such statements deal with future events and are based on Alcobra's current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Alcobra could differ materially from those described in or implied by the statements in this press release. For example, forward-looking statements include statements regarding the continuation of development of MDX, the potential of MDX as an available therapy for ADHD, conducting additional Phase III studies for MDX, the potential to address and actually addressing the high placebo rate observed in the Phase III study discussed above, completion of other studies referred to in this press release, or statements regarding Alcobra's plan to consult with the FDA to design additional Phase III studies in ADHD and the results of such consultation. In addition, historic results of scientific research and clinical and preclinical trials do not guarantee that the conclusions of future research or trials would not suggest different conclusions or that historic results referred to in this press release would not be interpreted differently in light of additional research and clinical and preclinical trials results. The forward-looking statements contained or implied in this press release are subject to other risks and uncertainties, including those discussed under the heading "Risk Factors" in Alcobra Ltd.'s Annual Report on Form 20-F filed with the Securities and Exchange Commission ("SEC") on March 28, 2014, and in subsequent filings with the SEC. Except as otherwise required by law, Alcobra disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

CONTACT: U.S. Investor Contact LifeSci Advisors, LLC Michael Rice 646-597-6979 mrice@lifesciadvisors.com Media Inquiries Sam Brown, Inc. Mike Beyer 312-961-2502 mikebeyer@sambrown.com Israel Investor Contact Alcobra Investor Relations Debbie Kaye +972-72-2204661 debbie@alcobra-pharma.com

Source:Alcobra Ltd.

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