NICE Recommends Takhzyro as Preventive Treatment for HAE Attacks

The National Institute for Health and Clinical Excellence (NICE) has recommended Takhzyro (lanadelumb) as a preventive treatment for hereditary angioedema (HAE) attacks in patients 12 and older, under certain conditions.

NICE’s final appraisal determination (FAD) states that Takhzyro should be used only if:

• patients are eligible to receive preventive treatment with C1-inhibitor (C1-INH) protein;
• the medication is administered at the lowest dosing frequency compatible with the product characteristics;
• the company continues to provide the medication according to the commercial arrangement.

This FAD will be included in the final guidance document to the NHS in England and Wales, which is expected to be published in October. Based on NICE’s positive recommendation, the NHS should make Takhzyro available to patients living in England within three months of that publication.

“HAE attacks are unpredictable, painful and debilitating. Today’s recommendation from NICE means that people living with HAE across England and Wales have another medication that gives them the chance to lead a full and active life. We hope the NHS and Healthcare Professionals will provide swift access to patients who could benefit from this new treatment,” Laura Szutowicz, CEO of HAE UK, said in a press release.

HAE is a rare genetic disorder characterized by sudden and recurrent episodes of swelling in the face, tongue, hands, feet, gastrointestinal tract, genitalia, and upper airways.

The disease is caused by a lack of functional C1-INH protein, resulting in the continuous production of an enzyme called kallikrein, which raises the levels of bradykinin, a peptide that regulates blood pressure and inflammation by dilating blood vessels. Bouts of swelling occurring during HAE attacks are caused by the overproduction of bradykinin.

Shire’s Takhzyro is a human antibody that works by inhibiting the activity of kallikrein and preventing the overproduction of bradykinin. It has been approved as a preventive treatment for HAE attacks in the U.S., Canada, European Union, Australia and Switzerland, with more regulatory submissions currently underway in other countries across the globe.

Takhzyro also has been the first preventive medication for HAE attacks that may be self-administered by patients at home through a single under-the-skin injection, every two to four weeks. Previous clinical trials have reported that Takhzyro reduced the frequency of HAE attacks by 87% compared to a placebo, and significantly improved patients’ work productivity, sleep quality, and ability to socialize and engage in physical activities.

“The replacement of frequent intravenous injections with at-home subcutaneous administration every two to four weeks, and the chance of being attack free, means that lanadelumab has the potential to transform care for some patients. It represents a real step-change in the treatment and clinical management of patients who experience recurrent HAE attacks,” said Sinisa Savic, PhD, consultant in Clinical Immunology and Allergy.

NICE’s decision to recommend the use of Takhzyro as a preventive treatment for HAE attacks was based on data from the HELP-03 Phase 3 trial (NCT02586805). HELP-03 was a 26-week, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and effectiveness of Takhzyro at preventing HAE attacks in 125 patients.

The trial’s findings showed that Takhzyro reduced the frequency of HAE attacks by 87% when administered at 300 mg every two weeks, and by 73% when administered at 300 mg once-a-month, compared to a placebo.

An exploratory analysis also revealed that 44% of the patients receiving Takhzyro every two weeks remained attack-free during the 26 weeks of the study, whereas only 2% of those receiving a placebo attained the same outcome.

“Ensuring people living with rare diseases, such as HAE, have the best care and access to innovative treatments is of the upmost importance to us and this recommendation by NICE represents a huge milestone,” said Jon Neal, managing director of UK and Ireland Takeda. “Takeda is really proud to be able to bring this novel medication to those living with this extremely debilitating condition.”