Biotech Values

[DewDiligence]

A single injection enabled the patients to produce small amounts of Factor IX, enough that four of the six could stop the usual treatment, injections of Factor IX concentrate prepared from donated blood.

Clotting diseases are well suited to gene therapy because a patient needs only a small amount of the missing factor—typically less than 5% of normal—to enable the coagulation system to function effectively.

A serious problem with other delivery viruses is that they insert themselves randomly into chromosomes, sometimes disrupting a gene. The virus used by Dr. Nathwani’s team, known as adeno-associated virus-8, generally stays outside the chromosomes, so it should not present this problem. Still, patients will need to be monitored for liver cancer, a small possibility that has been observed in mice.

This explains why even the limited success reported in your post has taken so long to achieve.

Patients have little or no immunity to the adeno-associated virus, which infects rhesus monkeys. The virus has a propensity for making liver cells its target, which is good for the therapy because these cells are the natural producers of Factor IX. However, liver cells do not live forever and slowly replenish themselves, possibly limiting how long the therapy will last.

It’s not clear to me from the write-up whether patients who had a positive response without inflammation can be considered for retreatment when FIX production returns to near baseline, or whether retreatment is flat-out untenable.