Hurdles to Bringing Gene Therapies to Market: Giulio Cossu, MD

While standards for research are important to ensure safe and accurate testing for new gene therapies, some regulations may slow the advancement of gene therapies, Giulio Cossu, MD, FMedSci, FEAS, professor of regenerative medicine at the University of Manchester, explained. With cost being a chief concern for those in academic research, there is a need for discussion around these regulations, he said.

This transcript has been lightly edited for clarity.

Transcript

What are the biggest regulatory and manufacturing hurdles to bringing gene therapies to market, and how might they be addressed?

I've been thinking of that a lot, and I will use a Latin expression that says in medio stat virtus, which means the virtue is in the middle. Before, the patients were exposed to risk due to procedures that were not standardized and controlled in each detail. Now, I think because of the fear that things may happen, rules have been pushed to a level that is—in my opinion, and I've been doing this for about 30 years—absolutely unnecessary. One thing: if you are dealing with a patient who is immune deficient and one patient who is not, you cannot treat all the patients like they are immune deficient. And the number of controls—for example, I've been working in the UK and in Italy, and I have to say MHRA [Medicines and Healthcare Products Regulatory Agency] is much more pragmatic, at least in my experience, whereas IFA [Italian Medicines Agency], following the scheme of EMA [European Medicines Agency], requires certain tests to be done in GMP [Good Manufacturing Practices]. Now, whatever goes into the patient must be done under GMP conditions. But why does a test have to be done under GMP conditions and not GLP [Good Laboratory Practice]? Once you have validated the test and your test is reliable, you can cut the cost of one log. I haven't found anyone who has been able to explain to me why the vector copy number or the replication competent lentivirus tests have to be done under GMP.

This is something on which people should discuss, because otherwise, the cost makes academics like me out of the game. At most, you can do a phase 1, as we're doing now, but you cannot progress because you cannot raise enough money. And this is wrong. This is profoundly wrong, because the patients who died [after] gene therapy for neuromuscular disorders, for Duchenne [muscular dystrophy] or myotubular myopathy, had been treated in conditions that were absolutely perfect. The trials were absolutely approved, and everything had been done following the rules. But if you exceed the dose, then even water would become toxic. There's nothing wrong with AAV [adeno-associated virus] in itself; it's just you're giving too much, and you have toxicity due to an overdose of the drug. That is more important than having 30,000 changes of air per second, which seems completely unnecessary. Once you have a filter and you set it in a completely stable way and the operators are well trained, ticking the box that is GMP is pointless and expensive. At least, that is my opinion.