Metreleptin, an analogue of the hormone leptin, once formed a key part of Amylin Pharmaceuticals’ multi-agent strategy to develop an injectable treatment for obesity – an effort now consigned to the industry’s scrapheap.
But an investigator-sponsored trial has now highlighted the molecule’s promise in lipodystrophy, a rare disease, and this is where Amylin’s new owners, Bristol-Myers Squibb and AstraZeneca, seem to be heading. At a time when rare diseases are all the rage orphan drug status could also help overcome the major drawback of metreleptin’s short patent life.
Lipodystrophy is characterised by a loss of adipose tissue and an accumulation of fat in the blood or around organs, and patients have a lack of circulating leptin. It can either be genetic or acquired, and Bristol cites a prevalence of just a few thousand patients worldwide.
Amylin was bought jointly by Bristol and Astra for $7bn last year. The group’s obesity work had included the GLP-1 agonist exenatide, as well as metreleptin alone and in combination with pramlintide, but since obesity work was scrapped a couple of years back metreleptin has faded from prominence.
But the molecule has nevertheless made quiet progress, and just two months ago the licensee Shionogi secured approval in Japan for its use in lipodystrophy.
Amylin itself had completed a rolling US BLA in April 2012 for treating diabetes and/or hypertriglyceridemia in paediatric and adult patients with rare forms of lipodystrophy, but the FDA requested additional data. Bristol confirmed to EP Vantage that it is engaged with the agency to complete this BLA submission, but did not comment on how the latest metreleptin study enhanced the path to approval.
The trial had been carried out by the National Institute of Diabetes and Digestive and Kidney Diseases, and Bristol and Astra presented a subgroup analysis from it yesterday. Although the numbers are small they do appear to support the agent’s effect in paediatrics.
In 15 patients aged between 12 and 18, 12 months’ metreleptin caused statistically significant reductions in HbA1c and triglyceride levels, while in 12 patients under the age of 12 it numerically reduced levels of alanine aminotransferase and aspartate aminotransferase.
A boost to IP
Economic viability is another piece of the puzzle. It is possible that the decision to drop work in obesity had at least partially been due to metreleptin's short patent life; Bristol says the US composition-of-matter patent expires in 2016.
However, orphan status, which metreleptin has for lipodystrophy in the US and EU, offers a longer period of market exclusivity. Morgan Stanley analysts expect a US filing to be completed during the current quarter, and reckon on launch next year giving 2018 sales of $191m and peak revenue of $300m.
At present there is only one marketed drug for lipodystrophy – Merck KGaA’s tesamorelin (Egrifta) – although this is only approved to treat the HIV-associated form of the disease, and sold $23m last year. A deal between tesamorelin’s originator, Theratechnologies, and Ferrer has been scrapped after Ferrer withdrew an EU filing a year ago over long-term cardiovascular risks.
Metreleptin is the only other clinical-stage project, according to EvaluatePharma. Its developers look to have found a path forward in an indication that offers a decent period of near-exclusivity.