First treatment for children with Progeria or progeroid like syndromes (rare premature aging syndromes)
EMA has recommended granting a marketing authorisation in the European Union (EU) under exceptional circumstances for Zokinvy (lonafarnib), a treatment for patients with a genetically confirmed diagnosis of Hutchinson-Gilford Progeria Syndrome or progeroid laminopathies. Zokinvy is indicated for use in children one year of age and older.
Hutchinson-Gilford Progeria Syndrome is an ultra-rare multi-systemic ‘premature aging’ disease. It can be diagnosed by genetic testing but also based on a consistent pattern of clinical features, including limited growth, characteristic facial features such as a receding chin and a narrow, pointed nose, loss of hair and body fat, crowded teeth, small and fragile bones, and stiffness of joints. Most children die in their early teens due to severe cardiovascular complications at an average age of 14.5 years.
Hutchinson-Gilford Progeria Syndrome is ultra-rare. The incidence is approximately 1 in 4 million births with a prevalence of 1 in 20 million living individuals. Progeroid laminopathies are even rarer genetic diseases related to Hutchinson-Gilford Progeria Syndrome and have clinical features characteristic of physiological ageing, such as hair loss, short stature, cardiovascular diseases, and osteoporosis.
There are no medicines approved for the treatment of children with Hutchinson-Gilford Progeria Syndrome or with progeroid laminopathies. Patients are given the best standard of care to treat the signs and symptoms.
Zokinvy is administered to patients in hard capsules twice daily. Lonafarnib, the active substance of Zokinvy, is a specific inhibitor of farnesyltransferase (FTI). It was demonstrated that lonafarnib prevents the formation of aberrant progerin and progerin-like proteins in cells, thereby promoting maintenance of cell integrity and function. Furthermore, the progerin levels decreased under continued lonafarnib treatment. This means that the treated patients survive longer, by about half a year on average.
EMA’s human medicines committee (CHMP) based its recommendation for marketing authorisation on positive results, including increase in the lifespan of treated patients compared to historical untreated patients, from two separate single-arm cohorts on the survival benefit. The sample size in these cohorts is very limited given the rare nature of the condition.
Most of the patients in the clinical studies experienced moderate or severe adverse effects during the first 4 – 6 months of treatment. Most common adverse effects reported were vomiting, nausea, diarrhoea, fatigue, upper respiratory tract infection, decreased appetite and headache.
The marketing authorisation for Zokinvy was recommended under exceptional circumstances. In such cases, authorisation may be granted subject to certain specific obligations, to be reviewed annually. This happens when the applicant can show that they are unable to provide comprehensive data on the efficacy and safety of the medicinal product, either because of the rarity of the condition it is intended for, limited scientific knowledge in the area concerned, or ethical considerations involved in the collection of such data.
The opinion adopted by the CHMP is an intermediary step on Zokinvy’s path to patient access. The opinion will now be sent to the European Commission (EC) for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.
- The applicant for Zokinvy is EigerBio Europe Limited.
- Zokinvy was designated as an orphan medicinal product for the treatment of Hutchinson-Gilford progeria syndrome’ on 14 December 2018.
- Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designation should be maintained.