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.”
Clinical Observations
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.
Biomarker Data
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.
Copyright Business Wire 2015