Genervon GM6, but rather should we support a new FDA approval
paradigm. I completely agree that we need more data. The real
questions at hand are what data are required, how much, and how best
to collect it. A Phase 3 trial is an inferior process that yields
inferior data when compared to conditional approval.
Another clinical trial would suffer from the following weaknesses:
1) Common trial design would limit patient inclusion to those
diagnosed within 2-3 years of trial commencement and exhibiting a
Forced Vital Capacity > 60%. This trial design attempts to include
only those patients exhibiting "average" disease progression.
1a) In ALS, with an unknown number of disease variants and
pathogeneses, the notion of an "average" patient is scientifically
invalid and indeterminable.
1b) This gap in knowledge also precludes determining the number of
patients to recruit to create a valid sample population.
1c) This standard trial design yields no data on efficacy in late- or
early-stages of disease.
2) Conditional approval is a superior process to a Phase 3 trial, with
or without compassionate use or expanded access. It would yield
superior results sooner and at far lower cost.
2a) Conditional approval gives supervised access that will yield more
data sooner, across a broader spectrum of patient profile. A useful
comparison is the experience of the patient-led trial of lithium
carbonate, where patientslikeme.com was able to publish results more
than a year in advance of traditional clinical trials. The traditional
trials eventually confirmed the patient-led results. It is not
inconceivable that conditional approval would yield data from 2000+
patients, versus perhaps 400 in a Phase 3 trial plus compassionate
2b) A Phase 3 trial unnecessarily burdens the regulatory and medical
communities. Recruiting trial clinics, who must get approval from
their Institutional Review Boards, then recruiting trial participants,
takes thousands of person-hours without adding to patient safety.
Compassionate use requests would result in tens of thousands of pages
of paperwork for neurologists and the drug manufacturer. Costs to the
drug manufacturer are estimated to be $30 million, draining funds
from other research and development efforts.
A Phase 3 trial would result in inferior science, more slowly, at
higher cost. We are not asking for ALS nonprofits to support the Genervon GM6 product, but to support the conditional