Shire claims US okay for HAE blockbuster-in-waiting

Shire has the first approval in hand for its new hereditary angioedema drug lanadelumab, getting the nod from the FDA for use of the drug in HAE patients aged 12 and over.

Lanadelumab (formerly SHP643) will be sold as Takhzyro in the US and is being tipped as a future blockbuster for Shire. It is the first antibody for HAE and targets plasma kallikrein, an enzyme whose activity is uncontrolled in people with the disease and contributes to the oedema (swelling) of extremities, gastrointestinal tract and upper airways that characterises HAE.

The US regulatory has approved Takhzyro at a dose of 300mg given by subcutaneous injection every two weeks to prevent HAE attacks, with the option of spacing doses at four weeks once patients have been attack-free for at least six months.

The phase III HELP study showed that two-weekly dosing of the antibody by the patients themselves resulted in an 87% reduction in the mean frequency of HAE attacks compared to placebo, and reduced moderate to severe attacks by the same margin. At the end of the six-month assessment, 44% of patients on Takhzyro were attack-free, compared to 2% of the placebo group.

Shire is already a player in HAE therapy with three drugs already on the market for the disease that made $1.43bn in sales last year. Its current trio is Cinryze (C1 inhibitor [human]), an intravenous drug used to prevent HAE attacks, Firazyr (icatibant) which is used to treat acute attacks in adults, and Kalbitor (ecallantide), also for acute attacks.

Cinryze and Firazyr made up the bulk of those sales as Kalbitor was withdrawn in Europe in 2011, and with Firazyr facing generic competition the approval of Takhzyro – which is easier to administer and requires around 75% fewer injections – is a timely addition to the portfolio.

Meanwhile, Shire is also facing stiffer competition from the likes of CSL Behring’s Haegarda (C1-esterase inhibitor [human]) which was approved by the FDA as a two-weekly subcutaneous injection last year and – according to its developer – is picking up a 50% share of new prescriptions in the HAE prevention sector.

Some analysts believe Takhzyro will eclipse its older peers with sales of $2bn a year or more at its peak, and the approval has been warmly received by the HAE patient community.

“HAE attacks are painful, debilitating, and potentially life threatening,” commented Anthony Castaldo, president of the US Hereditary Angioedema Association. “Takhzyro provides the HAE community with a new option for the prevention of HAE attacks,” he added.

Shire added lanadelumab to its HAE pipeline after it bought Dyax Corp for $5.9bn in 2015, a deal that also added Kalbitor to its portfolio. The company is due to pay Dyax shareholders another $646m now that the antibody has been approved by the FDA.