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Shire plc: JAMA Publishes Complete Results of Phase 3 HELP Study™ Evaluating Lanadelumab as a Preventive Treatment for Hereditary Angioedema


  • Lanadelumab is a first-of-its kind monoclonal antibody approved in the U.S. and Canada to help prevent attacks of hereditary angioedema (HAE) in patients 12 years and older
  • Patients receiving lanadelumab 300 mg every two weeks had an 87% relative reduction in mean monthly attacks vs. placebo (0.26 vs. 1.97, n=27 vs. n=41)
  • All secondary endpoints (including relative reduction in the number of attacks requiring acute treatment or assessed as moderate or severe) were met
  • According to a post-hoc sensitivity analysis, 77% of patients receiving lanadelumab 300 mg every two weeks were attack-free during the steady-state period of the study

Dublin, Ireland – 27 November 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG), the leading global biotechnology company focused on rare diseases, today announced the Journal of the American Medical Association (JAMA) publication of complete results from the Phase 3 HELP Study™, a randomised, placebo-controlled trial evaluating the efficacy and safety of subcutaneously administered lanadelumab versus placebo over 26 weeks in 125 patients 12 years of age or older with hereditary angioedema (HAE). The HELP Study™ is the largest randomised controlled prevention study ever conducted to date in HAE.

Lanadelumab, which is approved under the brand name TAKHZYRO™ in the U.S. and Canada, is a first-of-its-kind monoclonal antibody that inhibits the activity of plasma kallikrein, an enzyme which is uncontrolled in people with HAE, to help prevent attacks. HAE is a rare, genetic and potentially life-threatening disorder that can result in recurrent attacks of oedema (swelling) in various parts of the body.

The study met all primary and secondary endpoints, with all three lanadelumab treatment regimens demonstrating statistically significant reductions in the mean monthly HAE attack rate compared to placebo. At 300 mg every two weeks, lanadelumab reduced the number of mean monthly HAE attacks by 87% relative to placebo (adjusted P<0.001). Patients receiving lanadelumab 300 mg every two weeks had 83% fewer moderate to severe attacks (vs. placebo), 87% fewer attacks that needed on-demand treatment (vs. placebo) and an 89% attack rate reduction (vs. placebo) from day 14 to 182.

“HAE can be an unpredictable disease which requires an individualised approach to treatment,” said Aleena Banerji, MD, Massachusetts General Hospital, Boston, Mass. and principal investigator of the clinical trial. “The findings from HELP support the use of lanadelumab as a subcutaneous prophylactic therapy to prevent HAE attacks in appropriate patients, helping address the need for new treatment options.”

A pre-specified, exploratory analysis showed that over the entire 26-week study period, 44% of patients receiving lanadelumab 300 mg every two weeks (n=12/27) were attack-free vs. 2% of patients receiving placebo (n=1/41). Additionally, in a post-hoc sensitivity analysis of the steady-state period of the last 16 weeks of the study, 77% of patients (n=20/26) receiving lanadelumab 300 mg every two weeks were attack-free vs. 3% of patients on placebo (n=1/37).

“We are excited about the potential of lanadelumab.” said Donatello Crocetta, Head, Global Medical Affairs, Immunology at Shire. “Data from HELP demonstrate the efficacy of lanadelumab in preventing HAE attacks over the entire duration of the study, with many patients remaining attack-free during the 16-week steady state period. We remain focused on our work to help make lanadelumab available to patients living with HAE in additional countries around the world.”

A clinically meaningful improvement was also observed in 81% of patients treated with lanadelumab 300 mg every two weeks based on the Angioedema Quality of Life Questionnaire (AE-QoL) compared to 37% of patients in the placebo group. The AE-QoL measures the impact of angioedema over a four-week period across four domains: fear/shame, functioning, fatigue/mood, and nutrition.

The most commonly reported treatment-emergent adverse events (excluding HAE attacks) in patients treated with lanadelumab during the entire treatment period were injection site pain (42.9%), viral upper respiratory tract infection (23.8%), headache (20.2%), injection site erythema (9.5%), injection site bruising (7.1%), and dizziness (6.0%). Most treatment-emergent adverse events (98.5%) were mild to moderate in severity. The most commonly reported treatment-emergent adverse events in patients treated with lanadelumab that were considered related to treatment were injection site pain (41.7%), injection site erythema (9.5%), injection site bruising (6.0%), and headache (7.1%). There were no deaths or related serious treatment-emergent adverse events.

About the HELP Study™
The HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ was a multicentre, randomised, double-blind, placebo-controlled parallel group trial that evaluated the efficacy and safety of subcutaneously administered lanadelumab versus placebo over 26 weeks in 125 patients 12 years of age or older with HAE.

The primary endpoint of the HELP Study™ was the number of investigator-confirmed HAE attacks over the entire 26-week study duration. Lanadelumab demonstrated that subcutaneous injections every two or four weeks reduced the mean monthly number of attacks across all three lanadelumab treatment arms studied: 300 mg every two weeks, 300 mg every four weeks, and 150 mg of lanadelumab every four weeks.

About Lanadelumab
Lanadelumab is a fully human monoclonal antibody that specifically binds and decreases the activity of plasma kallikrein. Lanadelumab is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. Lanadelumab is formulated for subcutaneous administration and has a half-life of approximately two weeks in patients with HAE.

Lanadelumab was approved under the brand name TAKHZYRO™ in the U.S. on 23 August 2018 and Canada on 19 September 2018 and additional regulatory submissions are ongoing worldwide.

U.S. Indication and Important Safety Information
INDICATION
TAKHZYRO (lanadelumab-flyo) is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients ≥12 years of age.

IMPORTANT SAFETY INFORMATION
Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, discontinue TAKHZYRO administration and institute appropriate treatment.

Adverse Reactions: The most commonly observed adverse reactions (≥10% and higher than placebo) associated with TAKHZYRO were injection site reactions consisting mainly of pain, erythema, and bruising at the injection site; upper respiratory infection; headache; rash; myalgia; dizziness; and diarrhea. Less common adverse reactions observed included elevated levels of transaminases; one patient discontinued the trial for elevated transaminases.

Use in Specific Populations: The safety and efficacy of TAKHZYRO in pediatric patients <12 years of age have not been established.

No data are available on TAKHZYRO in pregnant women. No data are available on the presence of lanadelumab in human milk or its effects on breastfed infants or milk production.

To report SUSPECTED ADVERSE REACTIONS, contact Dyax Corp. (a wholly-owned, indirect subsidiary of Shire plc) at 1-800-828-2088, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For full U.S. Prescribing Information, including the approved indication and important safety information, please visit https://www.shirecontent.com/PI/PDFs/TAKHZYRO_USA_ENG.pdf.

For full Canada Prescribing Information within Canadian Product Monograph, please visit https://www.shirecanada.com/-/media/shire/shireglobal/shirecanada/pdffiles/product%20information/takhzyro-pm-en.pdf.

Shire’s Commitment to Hereditary Angioedema
Shire is a dedicated, long-term partner to the HAE community with a decade of experience supporting patients. We are committed to serial innovation in HAE and our portfolio of products includes a number of therapy options to help meet the individual needs of those living with the disease. Beyond our focus on developing novel treatments, we provide specialised services and support offerings tailored to the HAE community. Learn more at shire.com.

For further information please contact:

Investor Relations

Christoph Brackmannchristoph.brackmann@shire.com+41 795 432 359
Sun Kimsun.kim@shire.com+1 617 588 8175
Scott Burrowsscott.burrows@shire.com+41 41 288 4195
Media
Katie Joycekjoyce@shire.com+1 781 482 2779
Emily Buntingemily.bunting@shire.com+41 79 866 9703

NOTES TO EDITORS

About Shire

Shire is the global biotechnology leader serving patients with rare diseases and specialized conditions. We seek to push boundaries through discovering and delivering new possibilities for patient communities who often have few or no other champions. Relentlessly on the edge of what’s next, we are serial innovators with a diverse pipeline offering fresh thinking and new hope. Serving patients and partnering with healthcare communities in over 100 countries, we strive to be part of the entire patient journey to enable earlier diagnosis, raise standards of care, accelerate access to treatment, and support patients. Our diverse portfolio of therapeutic areas includes Immunology, Hematology, Genetic Diseases, Neuroscience, Internal Medicine and Ophthalmics.

Championing patients is our call to action - it brings the opportunity - and responsibility - to change people’s lives.

www.shire.com

Forward-Looking Statements

Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, projected revenues, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:

  • Shire’s products may not be a commercial success;
  • increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire’s future revenues, financial condition and results of operations;
  • Shire depends on third parties to supply certain inputs and services critical to its operations including certain inputs, services and ingredients critical to its manufacturing processes. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;
  • the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
  • the nature of producing plasma-based therapies may prevent Shire from timely responding to market forces and effectively managing its production capacity;
  • Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
  • the actions of certain customers could affect Shire’s ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial conditions or results of operations;
  • failure to comply with laws and regulations governing the sales and marketing of its products could materially impact Shire’s revenues and profitability;
  • Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;
  • Shire’s patented products are subject to significant competition from generics;
  • adverse outcomes in legal matters, tax audits and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on the Shire’s revenues, financial condition or results of operations;
  • Shire may fail to obtain, maintain, enforce or defend the intellectual property rights required to conduct its business;
  • Shire faces intense competition for highly qualified personnel from other companies and organizations;
  • failure to successfully execute or attain strategic objectives from Shire’s acquisitions and growth strategy may adversely affect the Shire’s financial condition and results of operations;
  • Shire’s growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products;
  • a slowdown of global economic growth, or economic instability of countries in which Shire does business, could have negative consequences for Shire’s business and increase the risk of non-payment by Shire’s customers;
  • changes in foreign currency exchange rates and interest rates could have a material adverse effect on Shire’s operating results and liquidity;
  • Shire is subject to evolving and complex tax laws, which may result in additional liabilities that may adversely affect the Shire’s financial condition or results of operations;
  • if a marketed product fails to work effectively or causes adverse side effects, this could result in damage to Shire’s reputation, the withdrawal of the product and legal action against Shire;
  • Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire’s revenues, financial condition or results of operations;
  • Shire faces risks relating to the expected exit of the United Kingdom from the European Union;
  • Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs and may decrease its business flexibility;
  • the potential uncertainty resulting from the announcement by Takeda Pharmaceutical Company Limited on May 8, 2018 of a recommended offer for Shire under the UK Takeover Code; and

a further list and description of risks, uncertainties and other matters can be found in Shire’s most recent Annual Report on Form 10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in “ITEM1A: Risk Factors”, and in Shire’s subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire’s website.

All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.

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