Doctor Heras-Palou of the Royal Derby Hospital has had a particularly nasty problem.
A very rare hereditary disease called transthyetin-mediated amyloidosis (TMA) has been eating away at his hands.
Sticky protein builds in organs and around the nerves leading to a loss of function and ultimately a loss of the limbs themselves.
As luck would have it Dr Heras-Palou was himself a doctor specialising in hands.
So when he felt the tell-tale signs of numbness and tingling he quickly enrolled as a participant in the trial of a revolutionary new treatment.
Along with 225 other TMA sufferers he was given the drug Patisiran.
This acts upon RNA, the crucial mechanism within the cell that transmits information from the genes. By interfering with this pathway the cells produce fewer of the sticky amlyloid proteins.
The treatment has saved Dr Heras-Palou’s hands, and the trial was so successful that Patisiran, produced by US biotech Almylam, has now been approved by the FDA.
Patisiran is one of a new wave of gene therapies that is revolutionising the world of medicine. Last week we saw another instance.
Children with leukaemia that has failed to respond to conventional bone marrow transplants and other conventional treatments typically have little hope left.
But now they will have. The Novartis drug Kymriah will become available on the NHS.
Kymriah is also a gene therapy, although it works in quite a different way to Patisiran.
New generation of drugs
Kymriah is a CAR-T therapy. ‘CAR’ stands for Chimeric Antigen Receptor and ‘T’ stands for T cells, the workhorse cells of the immune system.
How do they work?
The cells of the immune system roam around the body and are supposed to recognise and then destroy hostile foreign bodies.
Cancer cells often evade them. This is partly because cancer cells are not foreign in the sense that they are not invaders from the outside (like viruses), but are simply normal cells that have gone wrong; and partly because cancer cells are sneaky and have evolved ways of tricking the immune system.
So one approach to cancer therapy is to make the immune cells more effective. If they will not recognise the cancer cells they must be made to do so.
Cue, CAR-T therapy.
First of all blood is drawn from the patient, from which T cells are extracted. Then new genes are delivered into these cells, which cause them to express certain proteins on their surface.
When infused back into the patient these new proteins act like docking mechanisms, homing in on the cancer cells, attaching the immune cell to the cancer cell like a limpet and initiating their destruction.
Kymriah and Patisiran are two of a completely new generation of drugs called gene therapies and investors need to know about them.
The crucial point about gene therapies is that they can be curative.
Rather than simply finding some way of alleviating symptoms or slowing the progression of a disease, gene therapies go right to the heart of the problem, the faulty functioning of cell, and correct the mechanism.
In trials they have been shown to do exactly this. Terminal patients have found that their cancer has completely gone.
Of course investors in this space need to be careful. First of all these new gene therapies are often only used to treat a handful of patients with a rare and life threatening condition.
Only a few hundred children will be given Kymriah, and so for its producer, Novartis, this represents a tiny market.
Next is the cost of gene therapies, at up to $400,000 a treatment.
This is not the barrier it seems, because if a one-off shot cures a patient once and for all and obviates the need for alternative expensive treatment further down the line it could prove a bargain.
But the price does highlight the high cost of producing gene therapies. In the case of Kymriah the procedure of taking blood from the patient, extracting, altering and then re-infusing T cells takes over a week.
Other problems include side-effects such as cytokine storms, and the fact that these therapies do not work for everyone.
So the true cost per cured patient is higher than the cost per treated patient.
Threat to the pharma industry
Nonetheless gene therapy is the future.
In the space of a few years it has progressed from being a nice idea, through promising trials to approved medicines and actual patient treatment. It is only going to get better.
Hundreds of trials are now underway. Researchers want to expand its indications, especially to tackle widespread problems such as diabetes, anaemia and lung cancer.
They want to make the homing in mechanism of the T cells more accurate so that it will be effective for more patients. They want to make the manufacturing process more efficient to bring down those costs.
I have no doubt that the industry will succeed in these endeavours. Gene therapy is still in its infancy, but it is already posing a threat to the pharma business.
The established model involves selling pills that are taken repeatedly over a number of years even if, as is common, they really don’t do any good.
In return for the $2bn cost of developing new medicines and the 10 year clinical trials pharmas are given years of patent protection.
But there is one particularly interesting feature of the new gene therapies.
They have not undergone traditional clinical trials, going through the Phase I, Phase II and Phase III, involving thousands of patients and comparing new treatments with existing ones or with placebo.
Unlike with pills you cannot give patients a bit of a gene therapy and then withdraw it if it does not work.
Once you have altered the mechanism of somebody’s cells there is no turning back. So the FDA has had to change the rules and it has proved to be very flexible.
Gene therapies have not been widely tested in massive trials. Instead they have been given to people in dire need, often facing imminent death and with no alternative available. They have nothing to lose.
As a result gene therapies have progressed very quickly into human subjects and these real life treatments, albeit on the basis of a small number of patients, have been enough to persuade the regulators to give marketing approval.
As a result it’s likely that many more gene therapies will rapidly advance into clinical use.
This is of course a great investment opportunity, but how to play it?
As I said these gene therapies are expensive to make and administer and their target populations are, as yet anyway, small. So for big companies like Novartis they do not push the dial very far.
There are of course other, newer companies that are exclusively pursuing new gene therapies. But there is another group that are providing the weapons of the revolution.
How to get the new genes into the cell? How to protect delicate live cells in transit from patient to laboratory? How to manufacture gene therapies in volume?
As readers of my Breakthrough Biotech Alert already know, some of these companies have already made their investors a lot of money.
But gene therapy is still in its early stages. There is still plenty of time to board the train.