Hyperlipoproteinemia Type IV

Genetic medicine, the delivery of genetic material as a therapeutic, has attracted record-breaking capital in biotech with ~$150 billion invested across ventures, IPOs, follow-ons, and M&A since 2013. This influx of capital, combined with some critical scientific breakthroughs, has led to the approval of multiple drugs that are changing the lives of patients worldwide. We think this could be just the tip of the iceberg given that there are more than 1,000 clinical trials underway, preclinical companies are raising record-breaking capital and multiple academic labs are working on the latest iteration of the technology. Importantly, while the first few drugs were approved for rare diseases (such as spinal muscular atrophy, inherited retinal diseases, familial hypertriglyceridemia), we now have two COVID19 vaccines approved (mRNA based) and multiple drugs poised to be approved for more prevalent diseases in cardiology, neurology, oncology, and autoimmunity. Outside of COVID19, which is expected to generate $50b+ in revenue this year, we expect genetic medicine to top $20b in revenue by 2026.

Genetic medicine, the delivery of genetic material as a therapeutic, has attracted record-breaking capital in biotech with ~$150 billion invested across ventures, IPOs, follow-ons, and M&A since 2013. This influx of capital, combined with some critical scientific breakthroughs, has led to the approval of multiple drugs that are changing the lives of patients worldwide. We think this could be just the tip of the iceberg given that there are more than 1,000 clinical trials underway, preclinical companies are raising record-breaking capital and multiple academic labs are working on the latest iteration of the technology. Importantly, while the first few drugs were approved for rare diseases (such as spinal muscular atrophy, inherited retinal diseases, familial hypertriglyceridemia), we now have two COVID19 vaccines approved (mRNA based) and multiple drugs poised to be approved for more prevalent diseases in cardiology, neurology, oncology, and autoimmunity. Outside of COVID19, which is expected to generate $50b+ in revenue this year, we expect genetic medicine to top $20b in revenue by 2026.

Beyond developing novel therapies for serious and rare diseases including FCS, Akcea is also dedicated to supporting the broader needs of the communities they serve. “You make my life so hard almost every single day,” Lindsey Sutton wrote in a letter to the illness that’s put her in the hospital more than 30 times. “I don’t think you’re aware of how scared of you I am. I cannot go an hour without stressing that, because of you, I am going to get pancreatitis.” Lindsey has familial chylomicronemia syndrome (FCS), an ultra-rare and potentially life-threatening disease. Its symptoms often occur daily and restrict the patient’s ability to participate in regular activities. These include abdominal pain, fatigue and impaired cognition. “One of the worst things is that I don’t feel like I have an outlet,” the teacher from California continued. “You have caused me to shut down, even around my family and best friends. You have helped me become a great actress, because I fake how I feel every day. Faking that I feel well is mentally draining, and I hate you for being the root of my health problems.” The science Also known as lipoprotein lipase deficiency, Fredrickson Type 1 hyperlipoproteinemia and familial hypertriglyceridemia, FCS is caused by impaired function of the lipoprotein lipase (LPL) enzyme. Because of limited LPL function, people with FCS cannot breakdown chylomicrons, a type of lipoprotein particle made up of 90 percent triglycerides. FCS patients typically have triglyceride levels above 880mg/dL. Normal levels for most adults are 150mg/dL or lower. In addition to a heightened risk of unpredictable pancreatitis and permanent organ damage, people with FCS report major emotional and psychosocial effects, including anxiety, social withdrawal, depression and brain fog. The challenges Diagnosed at 5-weeks old, Lindsey is one of the lucky ones. For patients like Justin Hastings, the disease eluded his doctors for years. “I had no idea what I had,” Justin explains in a testimonial video . “I started seeing an endocrinologist and gastrointestinal doctors but continued to have pancreatitis and continued to think I was going to die. I was ready to give up.” One day his wife, Naomi, did an internet search for secondary causes of hyperlipoproteinemia and learned about FCS. The symptoms — failure to thrive, chronic diarrhea, abdominal pain and recurrent pancreatitis — sounded just like those her husband had been experiencing for years. Within a week of sending additional blood tests to the Mayo Clinic, Naomi’s suspicions were confirmed. Justin had FCS. The treatment While no effective drug therapies have been approved for FCS, the United Kingdom recently granted a positive scientific opinion for the drug WAYLIVRA TM (volanesorsen), paving the way for patients to receive early access to this potentially life-saving medicine. Currently in development by Akcea Therapeutics , Inc., WAYLIVRA is designed to reduce the production of ApoC-III, a protein produced in the liver that plays a central role in the regulation of plasma triglycerides. Although early access to patients in the U.K. is a welcome development, more time is needed before WAYLIVRA or a similar drug is commercially available to treat conditions like FCS. “The process of developing any drug is challenging and requires extensive research and a deep understanding of the impact that a disease has on patients,” said Paula Soteropoulos, chief executive officer at Akcea Therapeutics , Inc., an affiliate of Ionis Pharmaceuticals. “Our connections with many individuals and families affected by FCS and with the leaders in treatment around the world have continually strengthened our commitment and our drive to find a treatment that will make a positive difference.” The importance of connectedness While an estimated 3,000 to 5,000 patients await a commercially available treatment for FCS, Akcea has started looking at non-pharmaceutical therapies for managing the illness. In a paper recently published in Expert Opinion on Orphan Drugs , researchers found that FCS patients who connected with each other — either in person or online — saw significant positive impacts on their quality of life. In the study, 50 participants were categorized into three groups (actively connected, passively connected and non-connected). They were then asked to self-report current or comparative assessments of their quality of life before and after connecting with FCS-focused support organizations. Using a customized retrospective web-based survey, researchers discovered that respondents showed significantly improved perceptions of overall health, disease outlook, motivation to take care of health and emotional well-being after connecting with a support organization. Any level of connection produced noticeable benefits, but active connection in the form of regular interaction with other patients was associated with the greatest improvements. Additionally, respondents reported higher levels of satisfaction with their primary treating physician after being connected. “In any disease state, and especially in rare diseases that are not well known or understood, it is essential to take steps to build a comprehensive assessment of how the disease affects patients and families,” said Ms. Soteropoulos. “All of us at Akcea see that as an essential part of our work.” Beyond developing novel therapies for serious and rare diseases including FCS, Akcea is also dedicated to supporting the broader needs of the communities they serve. This includes creating educational resources for patients such as FCSFocus.com , organizing in-person meetings and webinars to give patients and caregivers an opportunity to engage with one another, and collaboration with advocacy organizations such as The FCS Foundation . The company making a difference In addition to developing WAYLIVRA for FCS, the Akcea portfolio also includes TEGSEDI™, which was recently approved in the EU for treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis, a rare condition that affects an estimated 50,000 people worldwide. Symptoms can affect multiple parts of the body, including the nervous, cardiac, and gastrointestinal systems. “This is an incredibly exciting time for Akcea, with TEGSEDI now approved in Europe and regulatory reviews pending for both TEGSEDI and WAYLIVRA in the U.S.,” said Ms. Soteropoulos. “We have a dedicated team that is well positioned to bring TEGSEDI to the EU markets and to continue to advance our other clinical development programs.” In the last year alone, Akcea has expanded its workforce from 90 to about 250 employees. The company has established teams in nine countries and plans to move to a larger facility in Boston’s Seaport in September. “The next few years will be busy and include very exciting opportunities for team members of Akcea at every level,” Ms. Soteropoulos told BioSpace. “We are also dedicated to building a business that reflects the diversity and range of experience and skill that is reflected in the life sciences community. Nearly half of our board is women, more than half of our executive team are women, and more than 60 percent of our sales force is female.” Learn more Whether you’re planning your next career move, considering an investment opportunity or just want to learn more, the Akcea website is a great place to start. Job seekers can find out about opportunities and other life science companies by registering at BioSpace .