Akcea & Ionis Announce European Union Drug Approval for Ultra-Rare Disease

Akcea Therapeutics, Inc., an affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. recently announced that WAYLIVRA has received conditional marketing authorization from the European Commission (EC) as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for pancreatitis, in whom response to diet and triglyceride-lowering therapy has been inadequate. This authorization follows the positive opinion recommending approval provided by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). As part of the conditional marketing authorization, Akcea and Ionis will conduct a non-interventional post-authorization safety study (PASS) based on a Registry.

“WAYLIVRA is the only approved treatment for people with FCS and is a major milestone for the global FCS community. This also marks Akcea’s second drug approval in the last year. We are very grateful to all the patients and physicians around the world who participated in our clinical trials. Their insights about the challenges of this devastating disease, and their stories of how they have benefited from WAYLIVRA continue to motivate us,” said Paula Soteropoulos, Chief Executive Officer of Akcea Therapeutics. “We plan to launch WAYLIVRA in Germany this year followed by additional European countries in 2020. Our team is ready to deliver this treatment option to patients with FCS.”

FCS is an ultra-rare debilitating disease that can be life-altering. It is caused by impaired function of the enzyme, lipoprotein lipase (LPL), which results in significant risk and disease burden, including unpredictable and potentially fatal acute pancreatitis as well as chronic complications due to permanent organ damage. It is estimated that there are between 3,000 to 5,000 people living with FCS worldwide, with approximately 1,000 people living with FCS in Europe.

“WAYLIVRA is the only treatment available for patients with FCS, which makes this approval a landmark event for the global FCS community. Patients, their caretakers, and their families have been suffering without any therapeutic option. Now patients across Europe can access a medicine that may help address their severely elevated triglycerides, which can give them hope for better health. High triglycerides can lead to a multitude of severe and daily chronic symptoms, such as abdominal pain and increased risk of pancreatitis, which have a significant daily impact on people living with FCS,” added Jules Payne, Chief Executive at HEART UK and Chair of FH Europe.

WAYLIVRA is an antisense oligonucleotide drug designed by Ionis and co-developed by Akcea and Ionis to reduce the production of ApoC-III, a protein that regulates plasma triglycerides. WAYLIVRA is a self-administered, subcutaneous injection in a single-use, prefilled syringe.

“The approval of WAYLIVRA is truly an important moment for people affected by FCS and for all of us in medicine who specialize in treating lipid disorders,” said Dr. Eric Bruckert, Head of the Endocrinology and Prevention of Cardiovascular Disease department in Pitié-Salpêtrière Hospital in Paris, France. “Many clinicians are pleased to now have a treatment option available because of the significant burden of FCS on patients and their families.”

“WAYLIVRA is Ionis’ third medicine approved in just over two years. Our highly efficient and productive antisense technology has the potential to treat the untreatable by precisely targeting the root cause of disease. FCS is an example of a disease that our novel technology is ideally suited to address,” said Brett P. Monia, Chief Operating Officer at Ionis. “We are confident that our affiliate, Akcea, has built an expert team that is committed and ready to deliver WAYLIVRA to patients as soon as possible.”

The EC’s marketing authorization of WAYLIVRA is based on results from the Phase 3 APPROACH study and the ongoing APPROACH Open Label Extension study and is supported by results from the Phase 3 COMPASS study. Results from the APPROACH trial, the largest study ever conducted in patients with FCS, show that in comparison to placebo treatment with WAYLIVRA delivered clinically and statistically meaningful reduction in triglycerides over the study period. An analysis of patients with a history of recurrent pancreatitis events (≥ 2 events in the five years prior to Study Day 1) showed a significant reduction in pancreatitis attacks in WAYLIVRA-treated patients compared to placebo treated patients. The most common adverse events in the APPROACH study were injection site reactions and reductions in platelet levels. In addition to the open label extension study, there are also ongoing global Early Access Programs for WAYLIVRA.

WAYLIVRA is the only therapy indicated for people with familial chylomicronemia syndrome (FCS). Akcea is working to confirm a path forward for WAYLIVRA in the U.S. and Canada. 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 authorization of WAYLIVRA is based on results from the Phase 3 APPROACH study and the ongoing APPROACH Open Label Extension (OLE) study and is supported by results from the Phase 3 COMPASS study. Results from the Phase 3 APPROACH trial, the largest study ever conducted in patients with FCS, show that in comparison to placebo, treatment with WAYLIVRA reduced triglycerides 77% (-94% when compared to placebo). All patients in the trial maintained a low-fat diet.

WAYLIVRA 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 WAYLIVRA were events associated with injection site reactions and reduction in platelet levels/thrombocytopenia.

The WAYLIVRA Early Access Program (EAP) has been initiated in Europe, the U.S. and Canada and is currently enrolling eligible patients. Click here for more information on the WAYLIVRA EAP. For more information on WAYLIVRA, please visit www.WAYLIVRA.eu.

WAYLIVRA is also currently in Phase 3 clinical development for the treatment of patients with familial partial lipodystrophy, or FPL. Akcea anticipates reporting top-line data from this study in mid-2019.

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

As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world’s first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to treat a broad range of diseases including cardiovascular diseases, neurological diseases, infectious diseases, pulmonary diseases and cancer. For more information, visit www.ionispharma.com.

Akcea Therapeutics, Inc., an affiliate of Ionis Pharmaceuticals, Inc., is a biopharmaceutical company focused on developing and commercializing drugs to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI (inotersen) and advancing a mature pipeline of novel drugs, including WAYLIVRA (volanesorsen), AKCEA-APO(a)-LRx, AKCEA-ANGPTL3-LRx, AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six drugs were discovered by and are being co-developed with Ionis, a leader in antisense therapeutics, and are based on Ionis’ proprietary antisense technology. TEGSEDI is approved in the US, EU, and Canada. WAYLIVRA is approved in the E.U. and is currently in Phase 3 clinical development for the treatment of people with familial partial lipodystrophy, or FPL. Akcea is building the infrastructure to commercialize its drugs globally. Akcea is a global company headquartered in Boston, MA. For more information, visit www.akceatx.com.