Akcea response to draft negative guidance from NICE for WAYLIVRA▼® (volanesorsen), the only therapy for FCS, a devastating and ultra-rare disease

Akcea Therapeutics is engaged with the NICE process ahead of the next committee meeting to understand concerns around volanesorsen

LONDON, UK, 02 January 2020 – Akcea Therapeutics UK Ltd., an affiliate of Akcea Therapeutics, Inc., announced that the National Institute for Health and Care Excellence (NICE) has issued an Evaluation Consultation Document (ECD) stating that Waylivra▼® (volanesorsen) is not recommended for the treatment of Familial Chylomicronaemia Syndrome (FCS) in the National Health Service (NHS) in England. Although volanesorsen is innovative and the only authorised treatment for FCS, the recommendation from NICE states that it has concerns around the clinical evidence and high cost, and therefore did not consider it an appropriate use of NHS resources.

“We are disappointed with the draft guidance made by NICE today,” said Andy Caldwell, Country Manager, United Kingdom & Republic of Ireland, Akcea Therapeutics UK. “We will continue to work with NICE so this much-needed treatment can be provided to the patients that need it the most. As a patient-focused company, we are dedicated to supporting patients with FCS and those patients who are currently receiving volanesorsen through the Early Access to Medicines Scheme will continue to have access to the medication.”

FCS affects between 1 to 2 people per million.1 FCS is an ultra-rare life-altering genetic disease, caused by impaired function of the enzyme, lipoprotein lipase (LPL) which causes marked elevations in certain types of fat in the blood.2 It can lead to significant health risks, including unpredictable, severe abdominal pain and potentially fatal attacks of acute pancreatitis, as well as chronic complications such as permanent organ damage and diabetes.2 The severe physical implications of FCS and its long-term complications also have a significant burden on the day-to-day life of those affected, from an emotional, social and professional standpoint.3

 "NICE’s recommendation is a real blow for people living with FCS," said Jill Prawer of LPLD Alliance. "There are currently no treatments available for FCS. Volanesorsen is the only therapeutic option proven to change the lives of people affected by the condition. Without this support patients will be left alone to continue to struggle to cope with symptoms, including abdominal pain and pancreatitis - and the ever-present fear of both - which affects every area of their lives and the lives of those around them. We hope that some way will be found that will enable this desperately needed therapy to get to those who will benefit so much from it."

Volanesorsen is an antisense oligonucleotide drug designed by Ionis and co-developed by Akcea and Ionis to reduce the production a protein that regulates plasma triglycerides.

Volanesorsen was granted a marketing authorisation in May 2019 by the European Commission.4

For important safety information for volanesorsen, including method of administration, special warnings, drug interactions and adverse drug reactions, please see the European Summary of Product Characteristics (SmPC), which is available on the EMA website at www.ema.europa.eu.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Alternatively, search for MHRA Yellow Card in the Google Play or Apple App Store or contact the MHRA at yellowcard@mhra.gov.uk or 0800 731 6789 (10am to 2pm Monday to Friday only).

About volanesorsen

Volanesorsen, which received marketing authorisation in Europe in May 2019, is the only therapy indicated for people with familial chylomicronaemia syndrome (FCS). Volanesorsen is a self-administered, subcutaneous injection in a single-use, prefilled syringe. It is designed to reduce the production of ApoC-III, a protein that regulates plasma triglycerides and may also affect other metabolic parameters.4,5

Waylivra, a product of Ionis’ proprietary antisense technology, is designed to reduce the production of ApoC-III, a protein that regulates plasma triglycerides and may also affect other metabolic parameters. The European Commission’s marketing authorisation of volanesorsen was based on results from the Phase 3 APPROACH study5 and the ongoing APPROACH Open Label Extension (OLE) study6 and is supported by results from the Phase 3 COMPASS study.7 Results from the Phase 3 APPROACH trial, the largest study ever conducted in patients with FCS, show that in comparison to placebo, following three months of treatment, volanesorsen reduced triglycerides by 94%. All patients in the trial maintained a low-fat diet.5

Volanesorsen is associated with risk of thrombocytopenia. Enhanced monitoring is required to support early detection and management of thrombocytopenia. The most frequently observed adverse reactions (more than 10%) during treatment with volanesorsen were events associated with injection site reactions and reduction in platelet levels/thrombocytopenia.4,5

Volanesorsen was granted Promising Innovative Medicine status by the MHRA in October 2017. This was followed by positive Scientific Opinion and eligibility as an Early Access to Medicines Scheme (EAMS) treatment in March 2018, by the MHRA. Twenty-two patients to date have accessed volanesorsen treatment through the EAMS, provided by Akcea Therapeutics UK to the NHS at no cost.

About FCS

FCS is an ultra-rare disease caused by impaired function of the enzyme lipoprotein lipase (LPL) and characterised by severe hypertriglyceridemia (>880mg/dL or 10mmol/L) and a risk of unpredictable and potentially fatal acute pancreatitis.2 Because of limited LPL function, people with FCS cannot breakdown chylomicrons, lipoprotein particles that are 90% triglycerides.2 In addition to pancreatitis, FCS patients are at risk of chronic complications due to permanent organ damage, including chronic pancreatitis and pancreatogenic diabetes.2,8 They can experience daily symptoms including abdominal pain, generalised fatigue and impaired cognitions that affect their ability to work.2,3,9  People with FCS also report major emotional and psychosocial effects including anxiety, social withdrawal, depression and brain fog.2,3,9 Additional information on FCS is available through the LPLD Alliance at www.lpldalliance.org.

ABOUT AKCEA THERAPEUTICS

Akcea Therapeutics, Inc., an affiliate of Ionis Pharmaceuticals, Inc., is a biopharmaceutical company focused on developing and commercialising drugs to treat patients with serious and rare diseases. Akcea is commercialising Tegsedi® (inotersen) and Waylivra▼® (volanesorsen) and advancing a mature pipeline of novel drugs. Inotersen has regulatory approval in the U.S., E.U. and Canada and is now commercially available in nine countries including all four nations in the UK. Volanesorsen has regulatory approval in the E.U. and is under regulatory review in the U.S. for the treatment of familial chylomicronaemia syndrome (FCS).

AKCEA’S FORWARD-LOOKING STATEMENT

This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and the therapeutic and commercial potential of volanesorsen. Any statement describing Akcea’s goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement.

Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavour of building a business around such drugs. Akcea’s forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea’s forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea's programmes are described in additional detail in Akcea's annual report on Form 10-K, and its most recent quarterly report on Form 10-Q, which are on file with the SEC in the U.S. Copies of these and other documents are available from the Company.

In this press release, unless the context requires otherwise, “Ionis”, “Akcea,” “Company,” “Companies,” “we,” “our,” and “us” refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.

Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutic® Tegsedi▼® and Waylivra▼® are trademarks of Akcea Therapeutics, Inc.

 References

1 Heart UK. FCS. Available at: https://www.heartuk.org.uk/genetic-conditions/familial-chylomicronaemia-symdrome-fcs Last accessed December 2019.

2 Blom DJ, et al. (2018) Characterizing familial chylomicronemia syndrome: Baseline data of the APPROACH study. Journal of Clinical Lipidology; 12(5):1234-1243.

3 Davidson M, et al. (2017) The burden of familial chylomicronemia syndrome: interim results from the IN-FOCUS study. Expert Review of Cardiovascular Therapy; 15(5):415-423.

4 European Medicines Agency. Waylivra Summary of Product Characteristics. Available at: www.ema.europa.eu/en. Last accessed December 2019.

5 Gaudet D, et al. (2017) The APPROACH Study: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Volanesorsen Administered Subcutaneously to Patients with Familial Chylomicronemia Syndrome (FCS). Journal of Clinical Lipidology; 11(3):814-5.

6 ClinicalTrials.gov. The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients with Familial Chylomicronemia Syndrome. Available at: https://clinicaltrials.gov/ct2/show/NCT02658175. Last accessed December 2019.

7 ClinicalTrials.gov. The COMPASS Study: A Study of Volanesorsen (Formally ISIS-APOCIIIRx) in Patients with Hypertriglyceridemia. Available at: https://clinicaltrials.gov/ct2/show/NCT02300233. Last accessed December 2019. 8 LPLD Alliance. Symptoms of FCS. Available at: http://www.lpldalliance.org/about-fcs/symptoms/. Last accessed December 2019.

9 LPLD Alliance. More symptoms of FCS. Available at: http://www.lpldalliance.org/about-fcs/more-symptoms/. Last accessed December 2019.