PBS listing of 6-monthly Diphereline offers the potential to reduce CPP treatment burden

Tuesday, 15 Feb 2022


Diphereline (triptorelin embonate) 22.5 mg has recently been listed on the Pharmaceutical Benefits Scheme (PBS) for the treatment of central precocious puberty (CPP),1 offering a 6-monthly dosing option for gonadotropin-releasing hormone (GnRH) agonist therapy.

CPP is a GnRH-dependent condition that results in early onset and rapid progression of puberty in girls before 8 years of age and boys before 9 years of age.2,3 CPP is characterised by early physiological changes associated with puberty. These include thelarche and menarche in girls, increased testicular volume and penile growth in boys, and accelerated growth and tall stature in childhood, which often results in reduced height in adulthood due to premature fusion of growth plates.3

GnRH agonists have been the standard of care for CPP for over 30 years, with well-established safety and tolerability.3 However, regular in-clinic dosing requires patients to attend appointments several times per year, potentially resulting in disruption to school and work (for parents), and significant travel costs.

Potential benefits of less frequent dosing in CPP

Queensland paediatric endocrinologist A/Prof Tony Huynh welcomed the PBS listing of  Diphereline 22.5 mg. “This is great news for our clinic and patients because our catchment area is pretty broad: I saw a child recently who lives 1,200 km away in Longreach, so with the new 6-month preparation, we’re able to see them just twice a year rather than making the whole family come to the clinic four times [in one year],” he said.

A/Prof. Huynh also noted other potential advantages of Diphereline’s 6-monthly dose interval, including improved patient compliance and better allocation of clinic resources. “Seeing these kids every six months rather than every three [months] means there’s less chance of things getting in the way of appointments, but importantly for our clinic, where we treat a whole range of conditions, this dosing will allow us the time to see patients with other endocrine conditions more frequently as well,” he said.

In this young patient population, phobia of needles is a common consideration, explained A/Prof. Huynh: “Treatment for CPP isn’t particularly pleasant, and we certainly have a lot of kids who are so needle phobic that they have to be heavily sedated to get their injection. This is an enormous use of resources and time, involving multiple team members and even occupational therapists in some instances. Only having to do this every six months is a huge advantage for us”.

Treatment objectives in CPP

GnRH agonists halt the progression of puberty by causing down-regulation of pituitary GnRH receptors, leading to suppression of gonadotropin luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion, which in turn leads to suppression of oestradiol, progesterone and testosterone.3 Suppression of sex hormones thus halts the progression of puberty allowing it to be synchronised with age-related development.

When asked about aims of treatment, A/Prof. Huynh explained, “We have two main objectives when treating CPP. The first is to preserve final adult height, because if you go into puberty too early, you lose out on all of the pre-pubertal growth that you would have had. So, for a child who goes into puberty at the age of five, they could have lost out on over five years of growth. Our second objective is to ensure that the child has reached a level of emotional maturity to cope with puberty.”

Clinical data supporting 6-monthly Diphereline

While an important aim of treatment is slowing down premature bone maturation and growth, bone age determinations and growth velocity measurements are not sensitive enough to detect significant changes over the timeframes for most clinical trials. Thus, to determine the impact of GnRH agonists in CPP in clinical trials, LH release is measured.3

In a study on the safety and efficacy of 6-monthly Diphereline for CPP (N=44),3 41 patients (93.2%) showed pre-pubertal LH levels at Month 6 and maintained LH suppression until Month 12.3 All patients completed 48 weeks of treatment with no interruptions.3 Treatment-emergent adverse events were reported for 75% of patients and were mostly mild in nature.3

The study authors concluded that 6-monthly Diphereline is effective for both girls and boys in suppressing the pituitary-gonadal axis in children, with favourable effects on the progression of puberty.3

 Commenting on the study, A/Prof Huynh said, “Based on the data, I honestly cannot see a cohort of patients where we wouldn’t want to use the six month preparation. The only thing we would have to consider is adjusting our conversation with the patient and their parents about when to stop to prepare for timing the return of puberty.”

PBS eligibility criteria for Diphereline 22.5mg in CPP

Diphereline (triptorelin) 22.5 mg 6-month formulation is indicated and listed on the PBS for the treatment of children 2 years of age and older with CPP. 4 Eligible patients must have had onset of CPP prior to their 9th birthday (females) or 10th birthday (males), must be treated by a paediatric endocrinologist or endocrinologist specialising in paediatrics and must be under 12 years of age (females) or under 13 years of age (males) at the start of treatment.1 Full criteria are available on the PBS schedule.1

Disclosure

This article was sponsored by Ipsen Pty Ltd. Any views expressed in the article are those of the expert alone and do not necessarily reflect the views of the sponsor. Before prescribing, please review the Diphereline product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.

References

  1. Pharmaceutical Benefits Scheme: Triptorelin. Available from: https://www.pbs.gov.au/medicine/item/5297T. Accessed January 2022.
  2. Carel JC et al. Pediatrics 2009;123:e752–62.
  3. Klein K et al. J Pediatr Endocrinol Metab 2016; 29(11):1241–1248.
  4. Diphereline Approved Product Information.

Already a member?

Login to keep reading.

OR
Email me a login link
logo

© 2022 the limbic