New ALS drug
(`Motor Neuron Disease` or `MND` also known as `Lou Gehrig's disease`)
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A previously unknown problem protein has been discovered
A specifically designed new ALS drug, RCH4, successfully suppresses it
 ​RCH4 is available free of charge on compassionate basis depending on availability and location

Regulatory Authority approval

Every person diagnosed with ALS or Motor Neurone Disease should understand the following

Even if a magic drug which cured the condition were discovered and proven today, it would take years before it could be made available to patients. Unfortunately, far too long to wait as the time frame to get the required Regulatory Authority approval is greater than the average life expectancy of an ALS patient.

This is tragic, but we do not make the rules.
For understandable reasons, the Authorities and leglislators wish to protect society from bad drugs.
However, the Authorities and leglislators do not have ALS / MND themselves. If they did, the rules would be different.

The State has often been accused (perfectly logically) of protecting people to death.
To take an overview, without controls, in the whole population of the Nation, perhaps 50,000 people per year could be killed by "bad" drugs. But perhaps 500,000 people die because there are no drugs available in time.
An ethical dilemma.

Every drug must have Regulatory Authority approval in the country in which it is sold. In fact drugs are the most heavily regulated sector of any commercial, or indeed any, activity.

In every country there is strict leglislation to control substances which could change or modify the mental or physical status of a person (or animal).

Broadly, there are three catagories:
1/ Controlled or prohibited substances. These normally relate to narcotics or recrecrational drugs
2/ Prescription drugs, the use of which is subject to a prescription written by a medical doctor
3/ Over the counter (OTC) drugs which do not require a prescription, example Aspirin

Drugs which fall into either catagory 2 or 3 require Regulatory Authority approval which requires extensive clinical trials.

In the USA, there are the so-called "Right to Try" rules which offers access to a drug under certain conditions if the patient can persuade his or her doctor to issue a prescription.

Without Regulatory Authority approval, a drug will not be covered by health insurance or be supplied for free by National Health Services in countries where those services exist.

The road to obtaining approval of a drug and clinical trials​

The road to getting approval comprises of a number of steps:

Pre clinical phase
1/ The candidate drug must firstly show in laboratory experiments that its hypothised mode of action is valid and should work

An RCH4 example: A laboratory ELISA assay proving that the neurological excitotoxic agent rapidly increases in the prescence of the operationally termed MRCH antagonistic protein which RCH4 suppresses:-

2/ The drug must then be tested in transgenic animals (animals that have the disease) model to check that:
  • It is not obviously toxic
  • The disease symptoms in the animal are modified for the better
  • None the organs are adversly affected. They must all be closley examined. This is callled `Histology`

Clinical phases

Phase l clinical trial.
This is a safety trial where healthy volunteers are given doses of the new drug to see if they have any adverse reaction to it or if they demonstrate any side effects. It is customary to use healthy young adults because in the event of any unforseen problem, being young they have the optimum chance of making a complete recovery. A Phase l normally ranges from perhaps 10 to15 volumteers.

Phase ll clinical trial .
The objective is to further demonstrate evidence of safety but in addition the "end point" (the result which is hoped for) is a primary objective. In ALS, the gold standard for measurement of disease progression is the decline in the `ALSFRS-R` score. Traditionally, it is not cited as the end point for trials because the drugs being tested never achieved a slowing of the progression.
Instead, ALS trials threrfore tend to use other end points.

The Riluzole trial used time to start of mechanically assisted breathing as an end point.
Numerous unsuccessful drug trials looked for body fluid markers, or FVC (breathing) as the end point.

In the case of a rare disease where there is no effective drug for the condition, the Regulatory Authority may, at their discresion grant approval without a Phase lll clinical trial.
As stated above, the primary end point in ALS trials is normally the demonstration of the slowing of the ALSFRS-R score decline, i.e., slow the progression of the condition. Whether any trial has ever slowed the decline is very doubtful. There are a couple of drugs which slowed the decline - but only in very few patients in a carefully selected group. That this can realistically be extrapolated for the whole ALS population is highly unlikely. 

Phase lll clinical trial.
This is normally the final trial prior to obtaining Regulatory Authority approval.
The numbers of patients involved can number from hundreds to thousands - depending on the prevelance of the disease, how serious the disease is and if the drug is a new class (type). If a completely new technology, new discovery or other disruptive development and there is nothing else like it, there may be only hundreds of patients in the trial.
If it is, say, just another Aspirin, then there may be thousands of patients in the trial.

Failure of any trial to achieve the end point set out before the start of the trial means that the drug has failed and all the development costs and years of work are wasted.

Phase lV clinical trial.
After approval, it is customery for the Regulatory Authority to require ongoing collection and submission of data for a period of time after the new drug enters the market. If issues appear they will do a risk / benefit analysis of the side effects (or whatever) and then decide what action, if any, needs to be taken.