Takeda’s Takhzyro®▼ recommended on NHS for hereditary angioedema (HAE) in a Final Appraisal Determination (FAD). The health technology appraisal body in England and Wales, has issued its FAD recommending Takhzyro® (lanadelumab) subcutaneous injection as an option for preventing recurrent attacks of HAE in patients aged 12 years and older only if:
- They are eligible for preventive C1-esterase inhibitor (C1-INH) treatment in line with NHS England’s commissioning policy
- The lowest dosing frequency of lanadelumab is used in line with the summary of product characteristics
- The company provides lanadelumab according to the commercial arrangement.
HAE is a genetic condition characterised by swelling underneath the skin (angioedema) which can develop in as little as 30 to 40 minutes and can last up to five days. Swelling can occur on any part of the body; including hands and feet and affects one in 10,000 to one in 50,000 people in the UK according to HAEUK.
If a patient has HAE there is a 50% chance they will pass it on to their children, but it can also occur spontaneously, with no family history, through gene mutation. Patients with HAE may lack a regulatory protein called ‘C1-Inhibitor’ or their C1-Inhibitor has very low activity.
Lanadelumab is a first of its kind preventive treatment for this debilitating disorder which will be available to patients over the age of 12 who are experiencing two or more clinically significant attacks per week, over eight weeks, despite oral preventative therapy.
Lanadelumab is an antibody that binds and inhibits plasma kallikrein – an enzyme in the blood which participates in the surface-mediated immune system – and represents a new approach to the treatment of HAE which has been seen to significantly reduce the frequency of attacks.
This decision to recommend lanadelumab as a cost-effective use of NHS resources follows the submission of new evidence from the company during consultation on earlier draft recommendations.
The list price of lanadelumab is £12,420 per 300 microgram vial. The recommended starting dose is 300 mg lanadelumab every two weeks and is administered as a subcutaneous injection. The company has a confidential commercial arrangement (simple discount patient access scheme). This makes lanadelumab available to the NHS with a discount.
Key evidence behind the NICE recommendation for Takhzyro was data from the HELP-03 (Hereditary Angioedema Long-term Prophylaxis) Study™. In the 26-week Phase 3 HELP Study™, with 125 people with HAE, Takhzyro reduced the mean number of monthly HAE attacks by 87% compared with placebo when administered at 300 mg every two weeks and 73% compared with placebo when administered at 300 mg every four weeks (adjusted P>0.001).
A prespecified, exploratory analysis showed that over the entire 26-week study (Days 0-182), 44% (n=12/27) of patients taking Takhzyro 300 mg every two weeks were attack-free vs. 2% (n=1/41) of patients taking placebo. A post-hoc sensitivity analysis showed that 77% (n=20/26) of the patients receiving Takhzyro 300 mg every two weeks were attack-free during a steady-state (day 70-182) vs. 3% of patients on placebo (n=1/37). The HELP Study™ is the largest randomised, controlled clinical prevention study conducted to date in this rare disease.
The FAD is part of the final guidance to the NHS in England and Wales expected to be published in October 2019. Pending any appeals from key stakeholders, based on this positive recommendation the NHS should make Takhzyro available in England within three months of this date.
“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, UK and Ireland, Takeda. “Takeda is really proud to be able to bring this novel medication to those living with this extremely debilitating condition.”
Takhzyro is approved in the U.S. (August 2018), Canada (September 2018), E.U. (November 2018), Australia (January 2019) and Switzerland (June 2019) and additional regulatory submissions are ongoing worldwide.