vTv Therapeutics Inc. · NASDAQ:VTVT
vTv Therapeutics — Technical Presentation (July 2015)
13 slides from vTv Therapeutics's technical presentation, Jul 17, 2015
Slide 1: Azeliragon (TTP488): From Futility to Fast Track
Azeliragon (TTP488): From Futility to Fast Track An examination of the risks of futility analysis and the precautions that should be taken when executing and interpreting these analyses Marwan Sabbagh, MD; Aaron H Burstein, PharmD; Imogene Grimes, PhD; Carmen Valcarce, PhD; Eric A. Rose, MD; Rachell
Slide 2: Disclosures
Disclosures Dr Sabbagh receives research support from Lilly, Avid, Navidea, Functional Neuromodulation, Neuronix, Merck, Takeda, AstraZeneca, Roche, and Genentech. He is an advisor for Biogen, Lilly, vTv therapeutics, Avid, and Piramal. He receives royalties from TenSpeed/Random House. vTv Thera
Slide 3: RAGE Inhibition: A Novel Mechanism of Action for AD Treatment
RAGE Inhibition: A Novel Mechanism of Action for AD Treatment Select RAGE Ligands: • Advanced Glycation AZELIRAGON INHIBITS THE Endproducts (AGEs) RECEPTOR FOR ADVANCED • HMGB1 GLYCATION ENDPRODUCTS • Aβ (RAGE) • S100 Proteins Azeliragon Azeliragon inhibits RAGE Role of RAGE RAGE – Pre- and post-n
Slide 4: Azeliragon Phase 2b Study Design
Azeliragon Phase 2b Study Design Randomized, double-blind, placebo-controlled trial Mild to moderate AD (MMSE 14-26); N=399 – Power of 80% to detect a treatment benefit of 3 points on the ADAS-COG11 Stable background therapy with cholinesterase inhibitors and/or memantine Three arms (1:1:1)
Slide 5: Azeliragon Phase 2b Analysis
Azeliragon Phase 2b Analysis Pre-specified interim analyses – Safety: 50% of subjects completed 6 months; 100% completed or withdrew prior to12 months – Futility: 12 months after all subjects randomized Primary analysis specified in protocol and SAP – Analysis of covariance (ANCOVA) with multipl
Slide 6: Futility Analysis Decision Rules
Azeliragon Phase 2b Futility Analysis Decision Rules 18 month data used to assess probability of rejecting null hypothesis at the end of trial – Single-criterion conditional power computed based on assumed continuation of observed trend Conditional Probability Yes Terminate Study <10% No Yes Condi
Slide 7: 12-Month Interim Analysis Results
Azeliragon Phase 2b 12-Month Interim Analysis Results Conditional probability = 9.3% – Decision made to terminate study with subjects to discontinue dosing at next scheduled visit – While not a consideration in the futility decision algorithm, 5mg/day was associated with numerical favorable differ
Slide 8: Final Protocol Planned Analysis Demonstrates Azeliragon Met Pre-specified ADAS-COG11 Primary Endpoint
Final Protocol Planned Analysis Demonstrates Azeliragon Met Pre-specified ADAS-COG11 Primary Endpoint A D A S - C O G 1 1 C h a n g e f r o m B a s e lin e Protocol-planned analyses, using different IT T , M ild - t o - M o d e r a t e A D ( M M S E 1 4 - 2 6 ) methodologies to cope with missing d
Slide 9: On-Treatment Analysis
Azeliragon Phase 2b On-Treatment Analysis On-treatment analysis included all A D A S -C O G 1 1 O n - T r e a t m e n t , M ild - t o - M o d e r a t e ( M M S E 1 4 - 2 6 ) available on-treatment data where (la r g e r c h a n g e = m o r e w o r s e n in g ) “on-treatment” defined as date of 0 5
Slide 10: Mild (MMSE 21-26) Sub-group
Azeliragon Phase 2b Mild (MMSE 21-26) Sub-group Evaluation shows more pronounced efficacy in mild AD patients, including statistically significant improvement in both ADAS-COG11 and CDR-SB A D A S - C O G 1 1 C h a n g e f r o m B a s e lin e C D R -S B M ild A D ( M M S E 2 1 - 2 6 ) M ild A D (
Slide 11: Futility Analysis
Futility Analysis The discordance between the positive results of the final analysis and the prediction from the futility analysis is most likely resolved understanding the specific attributes of the futility analysis Data were used only from patients who had completed 18 months of treatment at
Slide 12: STEADFAST Study: Phase 3 Clinical Trial Under SPA
STEADFAST Study: Phase 3 Clinical Trial Under SPA Randomized, double-blind, parallel group, 18-month trial in 800 patients with mild AD (MMSE 21-26) – Enrollment commenced in April 2015 Two independently powered sub-studies (sub-study A and sub-study B) under a single protocol: – Each study (n=4
Slide 13: Conclusions
Conclusions Futility analyses in AD trials may be misleading and argue for conducting the full analysis plan even when futility criteria are met The results of the ITT analysis, the four sensitivity analyses, the on- treatment analysis and the mild sub-group analysis justify further investigatio
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