Spotlight on Ravulizumab 2- use in specific populations

Following on from the first spotlight on ravulizumab article about its dosing (click here to see) now  the spotlight switches to its use in “specific populations”.

Firstly those aHUS patients who are pregnant. Pregnant women were excluded from Ravulizumab trials for PNH and aHUS so there is no data about birth defects, miscarriage or damage to foetus and mothers. Just an offsetting balance of advice that untreated aHUS has its risks. aHUS in pregnancy increases risks of adverse maternal outcomes, including preeclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including intrauterine growth restriction (IUGR), fetal death and low birth weight.But in animal testing ravulizumab at some dosing levels was found to increase abnormalities and dead and “moribund ” offspring.

At this stage there is nothing to suggest that what has been found out about eculizumab in humans is translatable to ravulizumab. Not even any anecdotes in the public domain so far. Of specific interest is the impact  of neonatal FC receptors through which Ravulizumab attains its  longer life. So a role for eculizumab may continue until resolution , or maybe even more long term!

As yet there is no data about it but it is known that products like Ravulizumab can cross the placental barrier and can inhibit the complement of the unborn child.

Although there is no evidence of ravulizumab in human milk ,  breast fed children may be  at risk of possible serious adverse reaction. It is advised that breast feeding should be  stopped during ravulizumab treatment and for at least 8 months after a  final ravulizumab dose.

So for those onsetting post- partum  and lactating , and also those whether “in treatment” or not making family plans there are considerations to be made.

There is an “irony” that Ravulizumab’s commercial production, which like for so many therapeutic antibodies , Including eculizumab ,is based on the use of the ovarian cells of  the Chinese hamster, might be problematical for the pregnant aHUS patent population which is a significant proportion of the adult aHUS population.

The use of ravulizumab in another specific patient group , aHUS  children one month or older,  has been studied in “adequate and well controlled “ trials and its safety and efficacy is similar to adult patients. A spotlight on adverse reactions to Ravulizumab  will feature in a future news blog.

Treatment of older patients with later aHUS onset has not been sufficiently studied because of few numbers of that cohort in trials , although the oldest participant in the “311 trial” is reported  to have been 76.6 years old when  first treated.  No assessment was conducted  whether there is any difference in response to the drug. Nothing from clinical experience suggests there is a difference.

 

Note :Highlights of Ravulizumab use can be seen in this document https://alexion.com/Documents/Ultomiris_USPI.pdf