EU regulators back Chiesi drug for rare inherited disease

European regulators have recommended a licence for Chiesi’s Lamzede (velmanase alfa) as a treatment for alpha-mannosidosis, a rare inherited enzyme disorder that causes cell damage in many organs and tissues.

The European Medicines Agency’s CHMP scientific committee has recommended granting a marketing authorisation in the European Union (EU) for Lamzede as a long-term enzyme replacement therapy in adults, adolescents and children with mild to moderate forms of alpha-mannosidosis.

This is not Chiesi’s first venture into rare disease – the Italian pharma used to market Glybera, the world’s most expensive drug, in Europe for around a million euros per patient with another rare disease, familial lipoprotein lipase deficiency.

But Chiesi and partner uniQure pulled Glybera from the market last year after it proved a commercial flop, with only one patient reportedly receiving treatment.

There’s no word yet on pricing, as this will be decided in each member state should the drug get the green light from the European Commission in the coming weeks.

Patients affected by the alpha-mannosidosis may have intellectual disability, liver or spleen enlargement, distinctive facial features and skeletal abnormalities.

The symptoms range from mild to moderate and severe. Individuals with early onset severe and rapid progressive disease often do not survive beyond childhood, whereas those affected with the milder forms of the disease survive into adult life.

Alpha-mannosidosis is a rare disease estimated to occur in approximately 1 in 500,000 to 1 in 1,000,000 people worldwide.

There is currently no cure for alpha-mannosidosis, but patients with the less severe forms of the disease are managed with supportive care including symptom management, medical and surgical treatment of complications and physical therapy.

Lamzede is a recombinant human alpha mannosidase developed as an intravenous enzyme replacement therapy (ERT) for the treatment of alpha-mannosidosis, which aims to replace the function of the deficient enzyme in the body.

The ERT aims to normalise oligosaccharide levels in the body, to prevent progression of the disease and formation of abnormalities, as well as to improve a patient’s condition.

However, Lamzede does not cross the blood-brain-barrier and is thus not expected to have an effect on the neurological aspects of the disease, which is also reflected in the indication.

The benefits of Lamzede were assessed in a multi-centre, double-blind, randomised, placebo controlled, parallel group trial involving 25 patients. The benefits observed in patients after 52 weeks of treatment included a decrease of serum oligosaccharide to normal levels, improvement in exercise capacity and pulmonary function is some patients. The most common side effects were diarrhoea, fever and weight increase.

The observation period of one year is not considered sufficient to fully characterise the magnitude of the changes. As alpha-mannosidosis is a very rare disease, the CHMP agreed that it is not possible to provide comprehensive data on the efficacy and safety under normal conditions of use.

Therefore the committee recommended granting a marketing authorisation under exceptional circumstances, because there was not enough data for a standard procedure.

Chiesi must complete an open label study to further characterise the efficacy in patients under six years of age and develop an alpha-mannosidosis disease registry, to evaluate long-term effectiveness and safety of the treatment.

Lamzede is also subject to specific post-authorisation obligations and monitoring.

Because alpha-mannosidosis is a very rare disease, Lamzede was granted an orphan designation. As always at time of approval, this orphan designation will now be reviewed by EMA’s Committee for Orphan Medicinal Products (COMP) to determine whether the information available to date allows maintaining Lamzede’s orphan status and granting this medicine ten years of market exclusivity.

The CHMP opinion will now be sent to the European Commission, which is likely to grant a licence in the coming months.