Lipodystrophy, Familial Partial

The safety and efficacy of the asset in treating metabolic disorders linked to lipodystrophy syndromes were evaluated in an open-label, single-arm study. Credit: MikeSaran / shutterstock.com. Health Canada has approved Chiesi Group unit Chiesi Global Rare Diseases’ MYALEPTA (metreleptin for injection) to treat individuals with lipodystrophy, an ultra-rare condition. MYALEPTA is a replacement therapy adjunct to diet to address complications of leptin deficiency in patients with congenital or acquired forms of the disease. MYALEPTA can be used in adults and children aged two and above with confirmed congenital generalised lipodystrophy (Berardinelli-Seip syndrome) or acquired generalised lipodystrophy (Lawrence syndrome). It is also approved for patients aged 12 years and above with familial partial lipodystrophy (PL) or acquired PL (Barraquer-Simons syndrome). The treatment is intended for patients with metabolic disease who have not achieved adequate metabolic control with conventional treatments. MYALEPTA is originally developed by Amryt Pharma . Chiesi Group gained access to MYALEPTA through the acquisition of Amryt in April 2023. See Also: UK MHRA approves GSK’s momelotinib for myelofibrosis anaemia Germany’s Ministry of Health refutes accusations of worsening market conditions The safety and efficacy of the asset in treating metabolic disorders linked to lipodystrophy syndromes were evaluated in a long-term, open-label, single-arm study. The research was conducted under the supervision of the US National Institutes of Health. Weight decrease, hypoglycaemia and fatigue were the most commonly observed adverse drug reactions linked to the treatment. Chiesi Group Global Rare Diseases head Giacomo Chiesi stated: “We are very proud of the partnership that we have developed with Medison and applaud the team for their efforts to bring this innovative and important treatment to patients in Canada. “At the Chiesi Group, we are committed to creating a difference in the lives of patients with rare diseases and in collaboration with the Medison team, we have been able to achieve this for those living with lipodystrophy.”

BOSTON, Feb. 05, 2024 (GLOBE NEWSWIRE) -- Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases, is pleased to announce the Health Canada approval of MYALEPTA™ (metreleptin for injection). As an adjunct to diet, MYALEPTA is indicated as a replacement therapy to treat the complications of leptin deficiency in lipodystrophy (LD) patients with confirmed congenital generalised LD (Berardinelli-Seip syndrome) or acquired generalised LD (Lawrence syndrome) in adults and children two years of age and above. MYALEPTA is also indicated in adults and children 12 years of age and above with confirmed familial partial LD (PL) or acquired PL (Barraquer-Simons syndrome) with persistent significant metabolic disease for whom standard treatments have failed to achieve adequate metabolic control. MYALEPTA was developed by Amryt Pharma, which was acquired in April 2023 by the Chiesi Group, an international, research focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare disease and specialty care. “Patients living with lipodystrophy are often burdened with tremendous physical, psychological and emotional challenges and as a profession we have had little in our toolbox of treatments to help them,” said Dr. Robert A. Hegele, Endocrinologist, Professor of Medicine and Biochemistry, Western University. “The approval of MYALEPTA provides clinicians and patients with a treatment that directly impacts the underlying metabolic disorder, which will result in effective symptom control.” “We are very pleased that Medison has taken the initiative needed to secure MYALEPTA’s approval in Canada, offering patients new hope with a treatment specifically targeting the underlying cause of this rare condition,” said Dr. Sonia Rehal, science educator and patient advocate, Lipodystrophy Canada Foundation. “Being a lipodystrophy patient myself and having lost my mother and sister to complications from this devastating disorder, our work is helping to advocate on behalf of patients and caregivers.” About Lipodystrophyi Lipodystrophy syndromes are a diversified group of rare, potentially life-threatening disorders that affect how the body accumulates and stores fat. These syndromes are categorized into two main forms: generalized is characterized by the absence or progressive loss of fat (adipose) tissue, and partial where the tissue loss is more limited, typically impacting certain areas like limbs or upper body. Lipodystrophy is also categorized by etiology with inherited and acquired forms. The estimated prevalence of lipodystrophy syndromes is 1.3 to 4.7 cases per million worldwide. Patients with lipodystrophy present with a broad range of symptoms, which can vary depending on the type of lipodystrophy and the extent of fat loss. The most common symptoms include organ abnormalities (e.g. hepatic steatosis, nephropathy and pancreatitis) and metabolic abnormalities (diabetes, insulin resistance and hypertriglyceridemia). These severe metabolic abnormalities can lead to organ damage and higher rates of mortality. Additionally, patients experience other comorbidities such as reproductive dysfunction, psychological distress and pain. In March 2021, Medison, the creator and leader of the multi-regional commercial platform, extended its partnership with Amryt Pharma, adding Canada to their partnership in Israel. The multiregional partnership has continued, following Amryt Pharma’s acquisition by Chiesi Farmaceutici S.p.A. (“Chiesi”). “At Medison, our business model is built on partnering with emerging biotech companies in the pursuit of bringing highly innovative therapies to patients in international markets,” said Gil Gurfinkel, CEO at Medison. “We are proud to have played an instrumental leadership role, leveraging our multi-regional platform assets, to expand the global access of MYALEPTA to patients in Canada.” “We are very proud of the partnership that we have developed with Medison and applaud the team for their efforts to bring this innovative and important treatment to patients in Canada,” said Giacomo Chiesi, Head of Global Rare Diseases at the Chiesi Group. “At the Chiesi Group, we are committed to creating a difference in the lives of patients with rare diseases and in collaboration with the Medison team, we have been able to achieve this for those living with lipodystrophy.” “Patients in Canada with lipodystrophy have been waiting for MYALEPTA to become available for many years and we are very pleased to be able to make this announcement today,” said Pamela Minden, Country Manager at Medison Pharma in Canada. “The commercialization strength of our team, leading to the achievement of MYALEPTA’s approval, has once-again demonstrated the value we bring to our partners in support of patients with unmet medical needs.” About MYALEPTAii,iii The safety and efficacy of MYALEPTA for the treatment of metabolic disorders associated with lipodystrophy syndromes in pediatric and adult patients were evaluated in a long-term, open-label, single-arm study conducted under the auspices of the National Institutes of Health (NIH) in the United States. The observed primary efficacy results in patients with generalized lipodystrophy (GL) - congenital or acquired - included a change from baseline to month 12 in HbA1c of -2.2 per cent and a percent change from baseline to month 12 in triglycerides of -32.1 per cent. The observed primary efficacy results in the PL subgroup patients included a change from baseline to month 12 in HbA1c of -0.9 per cent and a percent change from baseline to month 12 in triglycerides of -37.4 per cent. The most commonly reported adverse drug reactions (ADRs) were weight decreased (17%), hypoglycaemia (14%), and fatigue (7%). Important and complete safety information about MYALEPTA can be found by accessing the Product Monograph here. Important Safety Information Indication MYALEPTA (metreleptin for injection) is indicated as an adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in lipodystrophy (LD) patients: with confirmed congenital generalised LD (Berardinelli-Seip syndrome) or acquired generalised LD (Lawrence syndrome) in adults and children 2 years of age and above with confirmed familial partial LD (PL) or acquired PL (Barraquer-Simons syndrome), in adults and children 12 years of age and above with persistent significant metabolic disease for whom standard treatments have failed to achieve adequate metabolic control. Contraindications MYALEPTA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. MYALEPTA is contraindicated in patients with general obesity not associated with confirmed generalised leptin deficiency, or confirmed partial lipodystrophy, or with HIV-related lipodystrophy. Most Serious Warnings and Precautions Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with MYALEPTA. The consequences are not well characterized but could include inhibition of endogenous leptin action and loss of MYALEPTA efficacy. Worsening metabolic control and/or severe infection have been reported. Test for anti-metreleptin antibodies with neutralizing activity in patients with severe infections or loss of efficacy during MYALEPTA treatment. T-cell lymphoma has been reported in patients with acquired generalised lipodystrophy, both treated and not treated with MYALEPTA. Carefully consider the benefits and risks of treatment with Myalepta in patients with significant hematologic abnormalities and/or acquired lipodystrophy. Hypoglycaemia risk with concomitant use of MYALEPTA with insulin and other antidiabetic medication. Large dose reductions of baseline insulin requirements may be needed in the first 2 weeks of treatment. Dose adjustments of other antidiabetic medications may also be needed to minimise the risk of hypoglycaemia. Closely monitor blood glucose in patients on concomitant insulin therapy, especially those on high doses, or insulin secretagogues and combination treatment. Hypoglycemia management should be reviewed and reinforced with patients when initiating MYALEPTA therapy. Acute pancreatitis: Discontinuation of MYALEPTA may result in worsening hypertriglyceridaemia and associated pancreatitis, particularly in patients with risk factors for pancreatitis (e.g. history of pancreatitis, severe hypertriglyceridaemia). If a patient develops pancreatitis whilst being treated with MYALEPTA, it is advised that MYALEPTA be continued uninterrupted, as stopping treatment abruptly may exacerbate the condition. When discontinuing MYALEPTA, tapering of the dose over a two-week period is recommended in conjunction with a low-fat diet. Autoimmune disorder progression / flares, including severe autoimmune hepatitis, have been observed in some patients treated with MYALEPTA. Leptin plays a role in immune system homeostasis. Acquired lipodystrophies are associated with autoimmune disorders including autoimmune hepatitis and membranoproliferative glomerulonephritis. A causal relationship between MYALEPTA treatment and the development and/or progression of autoimmune disease has not been established. Other relevant warnings and precautions Hypersensitivity reactions immediately after using MYALEPTA Benzyl alcohol toxicity in pediatric patients when reconstituted with BWFI. MYALEPTA contains no preservative when reconstituted with sterile Water for Injection (SWFI). Driving and operating machinery Pregnant women, women of child-bearing potential, nursing women Medication dosing errors in pediatric patients with small volumes of dosing Pediatrics – limited data in children aged 0 to 2 years with generalised LD and children aged 0 to 12 years with partial LD Geriatrics - limited information in patients of 65 years For more information Please consult the MYALEPTA Product Monograph at for important information relating to adverse reactions, drug interactions and dosing information that has not been discussed in this piece. The Product Monograph is also available by calling 1-800-696-1341. About Chiesi Global Rare Diseases Chiesi Global Rare Diseases is a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have a therapy for all diseases and acts as a force for good, for society and the planet. The goal of the Global Rare Diseases unit is to ensure equal access so as many people as possible can experience their most fulfilling life. The unit collaborates with the rare disease community around the globe to bring voice to underserved people in the health care system. For more information visit . About Chiesi Group Chiesi is an international, research-focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company’s mission is to improve people’s quality of life and act responsibly towards both the community and the environment. By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi’s commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we’re part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035. With over 85 years of experience, Chiesi is headquartered in Parma (Italy), operates in 31 countries, and counts more than 6,500 employees. The Group’s research and development centre in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden. About Medison Pharma Medison is a global pharma company focused on providing access to highly innovative therapies to patients in international markets. Medison is the first to create an international commercialization platform for highly innovative therapies, helping to save and improve lives by making the best available novel treatments accessible to patients in international markets. Medison has a track record of multi-territorial partnerships with leading pharmaceutical and biotech companies seeking to expand their global reach. To learn more visit . For additional information, please contact: Chiesi Media Group Contract Chiara Travagin Rare Communications Manager Tel: +39 348 8818985 Email: c.travagin@chiesi.com Canadian Media Inquiries: Sky Striar, LifeSci Communications Tel: 617-797-6672 Email: sstriar@lifescicomms.com i Akinci, B., Oral, E., et. al. Comorbidities and Survival in Patients with Lipodystrophy: An International Chart Review Study. J. Clin. Endocrinol. Metab. 2019, 104(11):5120-5135. ii Brown, R., Oral, E., et. al. Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. Endocrine. 2018 Jun;60(3):479-489. iii MYALEPTA Product Monograph.

- First global regulatory approval for treatment of this rare genetic disease - SOUTH PLAINFIELD, N.J., Dec. 1, 2022 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) announced today that the Brazilian Health Regulatory Agency, ANVISA (Agência Nacional de Vigilância Sanitária), has approved Waylivra™ (volanesorsen) as the first treatment for familial partial lipodystrophy (FPL) in Brazil. This is the first approval globally for Waylivra for the FPL indication. Waylivra is also approved in Brazil for the treatment of Familial Chylomicronemia Syndrome (FCS). "Waylivra's approval as the first treatment for FPL is an important milestone for FPL patients in Brazil," said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics. "This approval is another example of PTC leveraging its strong capabilities in Latin America to bring first of its kind transformational therapies to patients with high unmet needs." FPL is a rare genetic metabolic disease characterized by selective, progressive loss of body fat (adipose tissue) from various areas of the body leading to ectopic fat deposition in liver and muscle and development of insulin resistance, diabetes, dyslipidemia, and fatty liver disease1. FPL is a highly burdensome disease, leading to significant metabolic complications that are not managed by current therapies, and it is a distressing condition for the patient. ANVISA's approval for Waylivra for FPL was based on results from the Phase 2/3 BROADEN study in patients with familial partial lipodystrophy. The study met its primary endpoint demonstrating a statistically significant reduction in triglyceride levels in patients with FPL treated with Waylivra compared to placebo-treated patients. In the study, there was a mean reduction from baseline of 88 percent in triglyceride levels in patients treated with Waylivra compared to 22 percent reduction in placebo-treated patients at three months. Clinically meaningful and statistically significant reductions in triglyceride levels were sustained over 12 months of treatment in FPL patients. In addition to achieving the primary endpoint, the study achieved an important secondary endpoint of a statistically significant reduction in liver fat. About Waylivra™ Waylivra (volanesorsen) is a product of Ionis Pharmaceuticals, Inc.'s proprietary antisense technology. Waylivra has received conditional marketing approval in the European Union as a treatment for FCS. In addition, Waylivra has been granted Orphan Drug Designation by the European Medicines Agency for the treatment of FCS. The approval by ANIVSA for FPL is the first global approval for this indication. Waylivra has been in-licensed for commercialization in Latin America by PTC Therapeutics from Akcea Therapeutics, Inc., a wholly-owned subsidiary of Ionis. About Familial Partial Lipodystrophy (FPL) FPL is a rare lipid disorder characterized by abnormal fat distribution across the body and a range of metabolic abnormalities, including severe insulin resistance, dyslipidemia and hypertriglyceridemia, hepatic steatosis and, in affected women, features of hyperandrogenism. People with FPL often present with polycystic ovarian syndrome or unusually insulin-resistant diabetes and are at increased risk of acute pancreatitis in addition to long-term, progressive consequences including premature cardiovascular disease and liver disease, resulting in cirrhosis. They are unable to store fat or triglycerides in normal fat stores, so excess triglycerides are stored in the liver and muscle and accumulate at high levels in the bloodstream. About Familial Chylomicronemia Syndrome (FCS) FCS is a rare disease caused by impaired function of the enzyme lipoprotein lipase (LPL) and characterized by severe hypertriglyceridemia (>880mg/dL) 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. They can experience daily symptoms including abdominal pain, generalized fatigue and impaired cognition that affects their ability to work. People with FCS also report major emotional and psychosocial effects including anxiety, social withdrawal, depression, and brain fog. The lack of treatments specifically indicated for patients with FCS means that patients must rely on a very restrictive, low-fat diet in combination with lifestyle changes and control of other secondary causes of HTG, which generally do not guarantee the necessary quality of life for those who have FCS. Diet alone does not fully control TG levels and is not sufficient to mitigate the risk of pancreatitis and enzyme replacement therapy would be ineffective in FCS due to half-life limitations. About PTC PTC is a science-driven, global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC's ability to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. The company's strategy is to leverage its strong scientific expertise and global commercial infrastructure to maximize value for its patients and other stakeholders. To learn more about PTC, please visit us at and follow us on Facebook, on Twitter at @PTCBio, and on LinkedIn. For More Information: Investor Contact: Kylie O'Keefe +1 (908) 300-0691 [email protected] Media Contact: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, including with respect to the commercialization of its products and product candidates; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Waylivra. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. 1 Chan JL, Oral EA. Endocr Pract 2010;16:310–323 SOURCE PTC Therapeutics, Inc.