Actualización de la peticiónFDA Accelerated Approval of Genervon's GM604 for Use In ALSHighlights of GM6 Trials where statistical significance or strong trend are achieved
Nicholas GrilloSan Francisco, CA, Estados Unidos
20 ene 2015 — https://www.facebook.com/gm604forals Normally no one expect statistical significance data from small sample size of Phase 2A trials. Most trials have a hard time even finding a positive trend. But GM6 is so potent that there are multiple statistical significance data not only in one but two neurodegenerative diseases and not in clinical data and results alone but correlated biomarkers data and results as well in both trials. Genervon Safety and Efficacy Study 1. Safety and Efficacy GM604 is a 6 amino acid endogenous,peptide. It is very safe and tolerable as shown in Phase 1 (32 subjects), ALS,Phase 2A (12 subjects), PD Phase 2A (6 subjects), Stroke (28 of 36 subjects,,not yet un-blinded). AEs and SAEs are comparable to placebo, with no reported,drug related clinically serious adverse events. 2. Trophic Effect Axon regeneration in rat with 8 mm gap,in severed sciatic nerve, p<0.001 3. Tropic Effect Neurons preferentially,projected correctly to motor nerves instead,of cutaneous nerve, p<0.001 4. Endogenous neuroprotection at fetal development MNTF expression detected in human,placenta peaked at week 9 5. Protection against toxic factors in CSF of CNS diseases patients The human patient neuron survival,percentages (compared to baseline): ALS (175%), PD (198%) 6. Neuroprotection 13 studies with in vitro and in animal,models showing GM6 has neuroprotection efficacy in ALS, PD, stroke models,,p<0.001 7. PCR Study: GM6 modulates multiple CNS target genes PCR study of GM6 with SHSY5Y cells (neuroblastoma,cells) and microglia showed GM6 modulates up or down the expression by two,fold or more of many ALS related genes identified by the scientific,community, such as SOD1, TDP-43, FUS, Cystatin-C, tau etc. and Parkinson,Disease related genes such as BDNF. 8 ALS Biomarker: plasma total tau, reduced ALS Phase 2A, plasma total tau lower,than placebo at week 6 (p=0.0369) 9. ALS Biomarker: plasma TDP-43, reduced ALS Phase 2A, slope in plasma TDP-43,through week 12 in treated (-3.513 pg/mL/wk) is lower than placebo (0.493,pg/mL/wk), p=0.0078. 10. ALS Biomarker: plasma SOD1, reduced ALS Phase 2A, plasma SOD1 percentage,change is lower than placebo at week 2, p=0.0550 11. ALS Biomarker:,CSF SOD1, reduced ALS Phase 2A, slope change in CSF SOD1,in treated patient was -1.975 through week 5, placebo was 15.523 12. Clinical Trials Biomarker Data is consistent with In Vitro PCR Data The observed effects of GM604 on SOD1,are consistent with the neuroprotective properties of GM604 in previous,Genervon in vitro studies and in vivo SOD1 transgenic ALS,animal model studies. The observed effects of GM604 on cystatin C, Complement,C3 and TDP--43 are consistent with the neuroprotective properties of GM604,reported in previous Genervon in vitro studies, and suggests that,GM604 modulates numerous genes towards a more homeostatic expression level,for each gene in treated patients. 13. ALS Clinical data: ALSFRS-R treated vs historical placebo ALS Phase 2A, GM604 significantly reduced the decline in ALSFRS-R in,treated patients when compared to the rate of decline of a historical placebo,control in the Ceftriaxone trial (p=0.0047) 14. ALS Clinical data: FVC slowed down ALS Phase,2A, (1) at site 1 FVC reduction from baseline to week 12 was statistically,significant in lowering the GM604 treated group than the placebo group,(p=0.027). (2) At Site 1 FVC % change in decline reduced from baseline to,week 12 in all patients at both sites significantly, p=0.0359significantly,(p-0.0105). (3) GM 604 reduce the,decline in ALL patients FVC at both sites from screening to week 12 with,statistical significance favoring GM604 treated group. FVC Change from,baseline, p=0.0476. FVC % change from baseline, p=0.0359. 15. PD Biomarker data: BDNF, increased PD Phase 2A, GM6 significantly increased the neuro-protective biomarker BDNF at week 2 in a comparison between the treated and active placebo groups (p=0.035). 16. PD Clinical data: UPDRS total lowered (slowed down or reversed) PD Phase 2A, the change in UPDRS of,GM602-treated PD patients at week 12 was statistically significant when,compared to data from historical placebo PD patients (p=0.0085) in ELDOPA,trial. 17. PD Clinical data: UPDRS ADL, Schwab & England, Hoehn & Yahr and MOCA PD Phase 2A, the changes in 4 out of the 8,secondary clinical outcome measures (UPDRS ADL, Schwab & England, Hoehn,& Yahr and MOCA) in treated patients at week 2 (visit 6) were,statistically significant in the desirable direction of change at the,one-tailed level (alpha = 0.1) when compared to the changes measured in the,placebo group. 18. GM604 Effect Size,according to FVC Clinical Data Sample size calculation for Phase 3 is,9 subjects based on the effect size of percentage change in site 001 FVC at,week 12 from baseline. 19. GM604 Effect Size,according to TDP-43 Biomarker Data According to the same size effect (4,pg/ml/wk) as was observed in the Phase 2A trial, a sample size of only 12,patients for Phase 3 would be required to achieve statistically significant,results at an 80% confidence level based on a two-tailed test (alpha = 0.05).
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