New Data from Pivotal Phase 3 Study Investigating Lanadelumab as a Prophylactic Treatment for Hereditary Angioedema to be Presented at 2018 AAAAI/WAO Joint Congress
New Data from Pivotal Phase 3 Study Investigating Lanadelumab as a Prophylactic Treatment for Hereditary Angioedema to be Presented at 2018 AAAAI/WAO Joint Congress
- Data from the largest prevention study in HAE conducted to date to be presented in three poster sessions
- Findings show significant reduction of attacks and improvement in Angioedema Quality-of-Life scores in HAE patients receiving lanadelumab across all dosing regimens studied versus placebo
- Lanadelumab is currently under FDA priority review for approval; FDA decision expected in August 2018
Cambridge, Mass. – March 3, 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG) announced today new Phase 3 results from the HELP Study™, a global, multi-center, randomized, 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 hereditary angioedema (HAE). Lanadelumab is an investigational treatment being evaluated for the prevention of angioedema attacks in patients with HAE, a rare genetic disease characterized by recurrent swelling of extremities, gastrointestinal tract, and upper airways.
“The data presented today further support the overall clinical profile of lanadelumab, which has been shown to significantly reduce the number of monthly HAE attacks when administered subcutaneously every two or four weeks,” said Jennifer Schranz, Global Development Lead, HAE, Shire. “HAE places a large burden on those living with the disease. We believe that this investigational treatment, if approved, has the potential to transform the treatment landscape for people with HAE."
The HELP Study is the largest prevention study in HAE conducted to date. Data will be highlighted in three poster presentation discussions at the 2018 American Academy of Allergy, Asthma & Immunology (AAAAI) and World Allergy Organization (WAO) Joint Congress. Patients in the study with ≥ 1 attacks per month were randomized into one of four treatment arms to receive repeated subcutaneous administrations of lanadelumab 300 mg every two weeks, 300 mg every four weeks, 150 mg every four weeks or placebo in a 2:1 (lanadelumab to placebo) ratio.
“The data on lanadelumab continue to demonstrate the importance of controlling plasma kallikrein activity, which is chronically uncontrolled in those living with HAE – even between attacks,” said Marc Riedl, M.D., Professor of Medicine and Clinical Director at the US HAEA Angioedema Center at The University of California San Diego and clinical trial investigator. “With its targeted mechanism of action, lanadelumab, if approved, has the potential to significantly reduce the number of monthly attacks for people with HAE.”
Following is a brief description of each poster being presented at AAAAI and WAO.
Poster Presentation 151: Consistent Lanadelumab Treatment Effect in Patients with HAE Regardless of Baseline Attack Frequency in the Phase 3 HELP Study
Lanadelumab consistently achieved reductions in monthly attack rates compared to placebo, regardless of baseline attack rate and the dosing regimen.
In this analysis, patients were categorized by baseline attack rate, 38 of the 125 patients in the trial had a baseline attack rate of 1 to ˂ 2 attacks per month. Compared to placebo (n=12), patients taking 150 mg every four weeks (n=10) had a 51% reduction in attacks, patients taking 300 mg every four weeks (n=9) had an 80.4% reduction, and patients taking 300 mg every two weeks (n=7) had a 92.8% reduction.
Twenty-two patients had a baseline attack rate of 2 to < 3 per month. Compared with placebo (n=8), these patients had a 90.6% reduction in attack rates using 150 mg every four weeks (n=3), 77% with 300 mg every four weeks (n=5) and 88.2% with 300 mg every two weeks (n=6).
For patients with a baseline attack rate of ≥ 3 attacks per 4 weeks (n=65), patients taking 150 mg every four weeks had a 78.8% reduction in attacks (n=15). Patients receiving 300 mg every four weeks experienced a 70.8% reduction (n=15). Patients receiving 300 mg every two weeks had an 85.9% reduction (n=14) compared to placebo (n=21).
Poster Presentation 150: Lanadelumab in Patients Switching from Long-Term Prophylaxis with C1-Inhibitor (C1-INH)
This analysis of the HELP Study evaluated the efficacy of lanadelumab in patients who were previously using a C1-INH for long-term prophylaxis (LTP) and found that all lanadelumab dosing regimens significantly reduced attack rates versus placebo; the reductions were similar in magnitude to those who did not receive prior LTP. Patients 18 years of age and older who were previously on LTP underwent a two-week washout prior to entering the study.
Poster Presentation 152: Lanadelumab Markedly Improves Health-Related Quality of Life in HAE Patients
Health-related quality-of-life (HRQoL) was assessed as part of the HELP study using the Angioedema Quality-of-Life (AE-QoL) questionnaire, a validated, angioedema-specific instrument to measure impairment in HRQoL. The AE-QoL questionnaire was administered monthly; total and domain (functioning, fatigue/mood, fear/shame, and nutrition) scores were calculated. Responder rates were determined by use of the AE-QoL’s minimal clinically important difference (MCID=6).
The pooled lanadelumab group, which included patients across all dosing regimens, demonstrated a significantly greater reduction in total and domain AE-QoL scores, relative to placebo. The largest decrease in AE-QoL score (decrease indicates improvement) was observed in the functioning domain with a mean change of -29.28 for the pooled lanadelumab group compared to -5.41 for placebo. Items in the functioning domain included impairments in work, physical activity, spare time activities or social relations.
There was no evidence of a treatment effect for the EQ-5D-5L questionnaire, a non-validated, non-disease specific QoL tool.
In addition, a significantly higher proportion of patients in the pooled lanadelumab group achieved an MCID in total AE-QoL scores (70% versus 37% for placebo).
Shire recently announced that that the U.S. Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) and granted priority review for lanadelumab. The FDA is expected to provide a decision on lanadelumab by August 26, 2018, based on the Prescription Drug User Fee Act V action date. The European Medicines Agency (EMA) also granted accelerated assessment for lanadelumab.
About the HELP Study™
The HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ is an international, multi-center, randomized, double-blind placebo-controlled parallel group, Phase 3 trial that evaluated the efficacy and safety of subcutaneously administered lanadelumab versus placebo over the course of 26 weeks. The study population comprised 125 patients age 12 or older with HAE Type I or II who were randomized to one of four groups: 150 mg of lanadelumab every four weeks (150 mg Q4W), 300 mg every four weeks (300 mg Q4W), 300 mg every two weeks (300 mg Q2W), or placebo.
The most commonly reported treatment-related adverse events in patients treated with lanadelumab during the treatment period were injection site pain, viral upper respiratory tract infection, headache, injection site erythema, injection site bruising, and dizziness. Most adverse events were mild to moderate in severity. No treatment related serious adverse events (SAEs) or deaths were reported. One subject experienced two related severe TEAEs leading to discontinuation. There were no safety signals identified in terms of any clinical laboratory test abnormalities, vital signs, physical examinations, or ECGs.
Lanadelumab is an investigational fully human monoclonal antibody that specifically binds and inhibits plasma kallikrein1 and is being studied as a treatment for the prevention of angioedema attacks in patients 12 years and older with HAE. Lanadelumab is formulated for subcutaneous administration, and has a half-life of approximately 14 days in patients with HAE.2
Shire recently announced that that the U.S. Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) and granted priority review for lanadelumab. The FDA is expected to provide a decision on lanadelumab by August 26, 2018, based on the Prescription Drug User Fee Act V action date.
Shire’s Commitment to Hereditary Angioedema
Shire is a dedicated, long-term partner to the HAE community with nearly a decade of experience supporting patients. We believe people living with HAE deserve a right-fit approach to treatment and are committed to serial innovation. Our existing portfolio of products includes a number of therapy options to help meet the needs of those living with the disease. Beyond our focus on developing novel treatments, we provide specialized services and support offerings tailored to the HAE community. Learn more at shire.com.
For further information please contact:
|Christoph Brackmann||[email protected]||+41 795 432 359|
|Sun Kim||[email protected]||+1 617 588 8175|
|Robert Coates||[email protected]||+44 203 549 0874|
|Elizabeth Kalina||[email protected]||+1 781 482 2713|
|Gwen Fisher||[email protected]||+1 781 482 9649|
NOTES TO EDITORS
Shire is the global leader in serving patients with rare diseases. We strive to develop best-in-class therapies across a core of rare disease areas including hematology, immunology, genetic diseases, neuroscience, and internal medicine with growing therapeutic areas in ophthalmics and oncology. Our diversified capabilities enable us to reach patients in more than 100 countries who are struggling to live their lives to the fullest.
We feel a strong sense of urgency to address unmet medical needs and work tirelessly to improve people’s lives with medicines that have a meaningful impact on patients and all who support them on their journey.
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;
- Shire's ongoing strategic review of its Neuroscience franchise may distract management and employees and may not lead to improved operating performance or financial results; there can be no guarantee that, once completed, Shire's strategic review will result in any additional strategic changes beyond those that have already been announced; 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.
1 Kenniston JA et al. Inhibition of plasma kallikrein by a highly specific active site blocking antibody. J. Biol. Chem. 2014;289(34):23596-23608.
2 Banerji et al. Inhibiting plasma kallikrein for hereditary angioedema prophylaxis. N Engl J Med. 2017; 376(8):717-728.