PASADENA, Calif.--(BUSINESS WIRE)--Genervon Biopharmaceuticals LLC (“Genervon”) today announced that it has submitted results to the FDA of its single compassionate patient trial (GALS-C) following its Phase 2A (GALS001) double blinded, randomized, placebo controlled ALS clinical trial protocol NCT01854294 for its drug candidate GM6. The FDA approved this compassionate-use application for this patient (IND # 120052).
"Based on the encouraging results coming in from our GALS Phase 2A trial we were interested in testing GM6 in a late-stage patient," said Dorothy Ko, COO of Genervon. "Because of the tenacity in fighting ALS demonstrated by this patient over the past 10 years and his otherwise-robust health, we felt him to be a perfect candidate." He is a 46 year old male ALS patient who was first diagnosed with the disease in Q1 2005 and by Q3 2008 was quadriplegic and on a ventilator. He has said: “Every waking moment is a fierce battle between iron determination and utter despair.”
After a six-dose treatment of GM6 the clinical observation results of the GALS-C patient revealed small but significant improvements from baseline to week 12. At week 2 the patient’s speech video definitely showed clearer articulation than baseline. 2 Weeks after the final dose, patient’s swallow volume was increased 150%-200% to 25cc-30cc. The oral fluid consumption reported by the patient was improved, measuring 250cc total in 25cc increments without leakage. Mouth suction as measured by water column height was increased from 5-8cm to 10-15cm with both 1/8 and 1/4 inch drinking straws. Speech, swallowing, and suction were used as primary metrics based on the theory that the motor neurons servicing the tongue and lips, being some of the shortest, would show any improvement first. During the trial, no adverse side effects were noted.
The CSF biomarkers SOD1, Cystatin C and total tau results all showed below the normal range at baseline. At week 2, after the six-dose treatment of GM6, results showed that all three biomarkers were upregulated substantially towards the normal range showing disease modification.
In contrast to the GALS-C patient (diagnosed 10 years ago), the treated patients in GALS001 (diagnosed within 2 years) had showed that the CSF biomarker SOD1 and total tau were at high end of the normal range at the start of the trial. At week 2, after the completion of the six-dose treatment of GM6, the test results showed that both of these biomarkers were down regulated, showing disease modification. The CSF biomarker Cystatin C test results for GALS001 showed that they were at the low end of the normal range at the start of the trial and were up regulated by week 2, showing disease modification.
Biomarker data of the GALS001 patients randomized to the placebo cohort all showed abnormal levels. As the trial progressed their biomarker levels continued in the abnormal direction, demonstrating that without treatment the disease will continue to uniformly become worse.
Master Regulator Homeostasis Theory
Classical single target drugs are mono directional: agonist or antagonist. Genervon’s hypothesis is that the endogenous signaling master regulator GM6 can restore health by regulating/modifying multiple genes and their protein expression in the correct direction when they are above or below the normal range. This hypothesis has been difficult to prove, as most ALS patients are uniformly above or below the normal range for most CSF biomarkers.
However, the GALS-C patient is unusual, having survived 10 years when the average life expectancy is 3 to 5. His biomarkers were below the normal range where the GALS001 patients’ biomarkers were above and GM6 regulated both in the correct direction towards the normal range/level, the hallmark of homeostatic processes in healthy living organisms. "This is definite evidence of GM6 as a potent master regulator of neuronal homeostasis," said Ko.
About Genervon: Genervon is a privately held, clinical-stage biopharmaceutical company in California developing breakthrough multi-target biological drugs to address critical unmet medical needs in CNS disorders. Genervon has received both fast track and orphan drug designations for GM604 in the treatment of ALS.