Summary Basis of Decision for Tryngolza

Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for Tryngolza is located below.

The SBDs written for eligible drugs (as outlined in Frequently Asked Questions: Summary Basis of Decision [SBD] Project: Phase II) approved after September 1, 2012 will be updated to include post-authorization information. This information will be compiled in a Post-Authorization Activity Table (PAAT). The PAAT will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive. The PAATs will be updated regularly with post-authorization activity throughout the product life cycle. At this time, no PAAT is available for Tryngolza. When the PAAT for Tryngolza becomes available, it will be incorporated into this SBD.

Date SBD issued: 2026-04-13

The following information relates to the New Drug Submission for Tryngolza.

Olezarsen sodium

Drug Identification Number (DIN): DIN 02563886 - 80 mg/0.8 mL olezarsen, solution, subcutaneous injection

Theratechnologies Inc.

New Drug Submission Control Number: 297894

Submission Type: New Drug Submission (New Active Substance) - Priority Review

Therapeutic Area (Anatomical Therapeutic Chemical [ATC] Classification, second level): C10 Lipid modifying agents

Date Filed: 2025-05-09

Authorization Date: 2025-12-16

On December 16, 2025, Health Canada issued a Notice of Compliance to Theratechnologies Inc. for the drug product Tryngolza.

The market authorization of Tryngolza was based on quality (chemistry and manufacturing), non‑clinical (pharmacology and toxicology), and clinical (pharmacology, safety, and efficacy) information submitted. Based on Health Canada’s review, the benefit-harm-uncertainty profile of Tryngolza is favourable as an adjunct to diet for the treatment of adult patients with familial chylomicronemia syndrome to reduce triglyceride levels.

Tryngolza, a lipid modifying agent, was authorized as an adjunct to diet for the treatment of adult patients with familial chylomicronemia syndrome to reduce triglyceride levels. All patients enrolled in the pivotal Balance study for Tryngolza had genetically confirmed familial chylomicronemia syndrome.

Tryngolza is not authorized for use in pediatric patients (under 18 years of age), as no clinical safety or efficacy data are available for this population.

No clinically significant differences in the efficacy or safety of Tryngolza were observed in geriatric patients (65 years of age or older) compared to younger patients.

Tryngolza (80 mg/0.8 mL olezarsen) is supplied as solution and administered subcutaneously once a month. In addition to the medicinal ingredient, the solution contains disodium hydrogen phosphate, sodium chloride, sodium dihydrogen phosphate, hydrochloric acid, sodium hydroxide, and water for injection.

The use of Tryngolza 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.

The drug product was approved for use under the conditions stated in its Product Monograph taking into consideration the potential benefits and risks associated with its use. The Product Monograph for Tryngolza is available through the Drug Product Database.

For more information about the rationale for Health Canada's decision, refer to the Clinical, Non-clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.

Health Canada considers that the benefit-harm-uncertainty profile of Tryngolza is favourable as an adjunct to diet for the treatment of adult patients with familial chylomicronemia syndrome to reduce triglyceride levels.

Familial chylomicronemia syndrome is a rare, serious, autosomal recessive, inherited genetic disorder characterized by severely impaired lipoprotein lipase function, resulting in severe hypertriglyceridemia and hyperchylomicronemia. Patients with familial chylomicronemia syndrome typically have triglyceride levels that are approximately 10 to 100 times higher than the normal reference value of less than 150 mg/dL (<1.7 mmol/L), not otherwise explained by secondary factors such as obesity, alcohol consumption, insulin resistance, diabetes, other underlying diseases, or the use of certain medications. Diagnosis of familial chylomicronemia syndrome can occur at any age, and the condition has an estimated worldwide prevalence of approximately 1 to 13 per million, although prevalence rates vary by geographic region. The disorder is caused by homozygous, compound heterozygous, or double heterozygous, loss-of-function, null, or nonsense mutations in the lipoprotein lipase gene or in several genes that encode proteins that regulate lipoprotein lipase activity. Reduced lipoprotein lipase activity impairs triglycerides clearance, leading to chylomicrons accumulation in plasma and resulting in severe hypertriglyceridemia and hyperchylomicronemia, as large chylomicrons remain in the circulation, even after prolonged fasting. Hypertriglyceridemia and hyperchylomicronemia can lead to medical complications, most notably an increased risk of acute pancreatitis, as patients with familial chylomicronemia syndrome are prone to recurrent, potentially life-threatening episodes. In addition, patients with familial chylomicronemia syndrome frequently experience eruptive xanthomas, lipemia retinalis, and recurrent abdominal pain, while hepatomegaly and splenomegaly may also occur.

Although genetic testing is considered the definitive method for diagnosing familial chylomicronemia syndrome, it is not always feasible, and patients may not always have access to it. Whether genetically confirmed or not, patients consistently present with markedly elevated triglyceride levels and are at risk for complications such as pancreatitis.

The first-line of treatment for patients with familial chylomicronemia syndrome is a strict dietary fat restriction to less than 20 grams of fat per day, along with avoiding alcohol. Even short-term consumption of dietary fat or small amounts of alcohol can raise triglyceride levels and increase the risk of acute pancreatitis. Even among patients who do adhere strictly to the recommended diet, triglyceride levels often remain elevated, thereby sustaining an ongoing risk of acute pancreatitis. Niacin, fibrates, and statins are approved in Canada for the treatment of hypertriglyceridemia but are ineffective for managing severe hypertriglyceridemia associated with familial chylomicronemia syndrome, as they primarily work by increasing the activity of lipoprotein lipase, a protein which is absent or severely deficient in patients with familial chylomicronemia syndrome. Therefore, the treatment of hypertriglyceridemia in patients with familial chylomicronemia syndrome remains an unmet clinical need.

Olezarsen, is an antisense oligonucleotide-triantennary N-acetylgalactosamine (GalNAc3) conjugate. Antisense oligonucleotides are short, synthetic strings of nucleotides designed to prevent the expression of a targeted protein by selectively binding to the messenger ribonucleic acid (mRNA) that encodes the target protein, thereby degrading the mRNA and preventing translation. Olezarsen selectively binds to apolipoprotein C-III (apoC-III) mRNA, leading to degradation by ribonuclease H1, which results in a lack of apoC-III protein.

Apolipoprotein C-III is a glycoprotein synthesized principally in the liver and is a potent inhibitor of lipoprotein lipase, the primary enzyme responsible for hydrolyzing plasma triglycerides. In addition, apoC-III protein also regulates the metabolism of triglyceride-rich lipoproteins through lipoprotein lipase independent pathways. These pathways may play an important role in patients with familial chylomicronemia syndrome, who have a deficiency in lipoprotein lipase activity and markedly increased risk of acute pancreatitis. Targeting apoC-III with an antisense oligonucleotide is a new approach to treating familial chylomicronemia syndrome.

The efficacy of Tryngolza was demonstrated in a single pivotal study, ISIS 678354-CS3, herein referred to as the Balance study. This Phase III, randomized, double-blind, placebo-controlled, multicentre study enrolled 66 patients with genetically confirmed familial chylomicronemia syndrome, and fasting triglyceride levels of at least 880 mg/dL (≥10 mmol/L). Following a screening and run-in period during which patients adhered to a diet containing no more than 20 grams of fat per day, participants were then randomly assigned to receive either Tryngolza 50 mg or Tryngolza 80 mg in a 1:1 ratio. Each cohort was then further randomized in a 2:1 ratio to receive monthly doses of Tryngolza or a matching volume placebo, respectively.

The primary efficacy endpoint was the mean percent change in fasting triglyceride levels from baseline to Month 6 compared to placebo. Of the 66 patients enrolled, 23 patients received a placebo, 21 patients received Tryngolza 50 mg, and 22 patients received Tryngolza 80 mg every 4 weeks.

The results from the Balance study showed that the placebo-adjusted percent change in fasting triglycerides from baseline to Month 6 for the Tryngolza 80 mg treatment group versus placebo was ‑42.5% (95% confidence interval [CI]: -69.085, -17.921) favouring Tryngolza 80 mg over a placebo with a statistically significant p-value <0.05. Tryngolza 50 mg treatment group compared to the placebo group was not statistically significant. This dosage strength was not proposed for market authorization by the sponsor.

Other study endpoints included a comparison of acute pancreatitis events at Month 12 after initiation of Tryngolza treatment versus placebo. At Month 12, a relevant reduction in the incidence of acute pancreatitis was observed, with 11 events reported in the placebo group and one event reported in the Tryngolza 80 mg treatment group.

In study ISIS 678354-CS8, a Phase IIb, randomized, double-blind, placebo-controlled study, 154 patients with hypertriglyceridemia and an established or increased risk of atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia who did not have familial chylomicronemia syndrome were randomized to receive either Tryngolza 50 mg and 80 mg administered once every 4 weeks over a 53-week treatment period. The primary efficacy endpoint, consistent with the Balance study, was the percent change in fasting triglyceride levels from baseline to Month 6 compared with placebo. The results from the ISIS 678354-CS8 study demonstrated a reduction in triglyceride levels in patients with, or at high risk of, atherosclerotic cardiovascular disease who did not have familial chylomicronemia syndrome.

Although the Balance study enrolled only patients with genetically confirmed familial chylomicronemia syndrome, Health Canada accepted a revised indication based on the rationale that not all patients with familial chylomicronemia syndrome have access to genetic testing. However, because the Balance study included only genetically confirmed familial chylomicronemia syndrome patients, a limitation-of-use statement was added to the indication to inform the prescriber.

The safety profile of Tryngolza was evaluated based on safety data from the Balance study and two interim open-label studies, ISIS 678354-CS13 and ISIS 678354‑CS7. The ISIS 678354-CS13 study is an ongoing the open-label extension of the Balance study, in which all patients with familial chylomicronemia syndrome continued or switched to Tryngolza 80 mg. The ISIS 678354-CS7 is an ongoing open-label study in patients with familial chylomicronemia syndrome who were previously treated with volanesorsen.

The most common adverse reaction in the combined safety analysis (89 patients) were injection site erythema (17%), chills (7%), myalgia (7%), injection site pain (6%), and hypersensitivity (2%). Serious adverse reactions that were reported included treatment emergent bleeding events (2%), hepatic adverse events (1%), and sudden death (1%). No deaths were considered related to study drug.

In the Balance study (66 patients), the most common adverse reactions occurring in at least 5% of patients, and that occurred more frequently in patients treated with Tryngolza (43 patients) compared to patient treated with placebo (23 patients) were injection site reactions (19% vs 9%), arthralgia (9% vs 0%), and platelet count decrease (12% vs 4%). These adverse reactions have been included in the Product Monograph for Tryngolza. Adverse reactions leading to treatment discontinuation occurred in 7% of patients receiving Tryngolza, compared with 0% of patients receiving a placebo. The most common reason for discontinuing Tryngolza was hypersensitivity reactions.

Adverse events of special interest included thrombocytopenia. In the Balance study, the proportion of patients who experienced thrombocytopenia treatment-emergent adverse events (TEAEs) was higher in the Tryngolza 80 mg group (3 [13%] patients) compared with the placebo group (1 [4.3%] patient). Overall, a greater proportion of patients in the Tryngolza 80 mg group (59.1%) experienced two or more episodes of platelet counts below the limit of normal compared to the placebo group (30.4%). However, a similar proportion of patients in the placebo group (13%) experienced a platelet count reduction of at least 50% in the Tryngolza 80 mg (13%) treatment group. Patients with thrombocytopenia TEAEs did not experience concurrent major bleeding events. A recommendation to obtain a baseline platelet count and monitor platelet levels during treatment as clinically necessary was included in the Product Monograph for Tryngolza. One death was reported in the Balance study, a sudden death in a patient treated with Tryngolza 50 mg, that the study investigator deemed as unrelated to the study drug.

A modest increase in low-density lipoprotein cholesterol, apolipoprotein B, fasting glucose and hemoglobin A1C were observed over time with Tryngolza treatment in the familial chylomicronemia syndrome population in the pivotal study. These have been included in the Product Monograph for Tryngolza with a recommendation to obtain baseline levels and monitor during treatment with Tryngolza, as clinically indicated.

Major adverse cardiovascular events (MACE) were numerically higher in patients treated with Tryngolza in the supportive study carried out in a non-familial chylomicronemia syndrome population with atherosclerotic cardiovascular disease (ASCVD) or at increased risk of developing ASCVD, Study ISIS 678354-CS8. No familial chylomicronemia syndrome patients treated with Tryngolza experienced any components of adjudicated MACE events, including cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and arterial revascularization, that were assessed as related to study drug. It was recommended in the Product Monograph for Tryngolza to assess the patient’s comorbidities prior to initiating Tryngolza treatment.

Safety data on the use of Tryngolza in patients with familial chylomicronemia syndrome were limited at time of market authorization, due to small sample sizes in the clinical trials as a result of the rare disease nature of this condition. While the risk of thrombocytopenia and bleeding events or, hepatotoxicity or renal toxicity may not have been fully elucidated during clinical development of Tryngolza, these adverse reactions have been identified with other antisense oligonucleotides and therefore cannot be completely excluded.

A Risk Management Plan (RMP) for Tryngolza was submitted by Theratechnologies Inc. to Health Canada which is designed to describe known and potential safety issues, to present the monitoring scheme, and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP was considered to be acceptable. Thrombocytopenia and hepatotoxicity have been included in the Risk Management Plan as important potential risks warranting close monitoring in the post-marketing setting.

The submitted inner and outer labels, package insert, Patient Medication Information section of the Product Monograph for Tryngolza met the necessary regulatory labelling, plain language, and design element requirements following the requested revisions.

Overall, Tryngolza has been shown to have a favourable benefit-harm-uncertainty profile based on the Balance study. The identified safety issues are managed through labelling and clinical monitoring. Appropriate warnings and precautions are in place in the Product Monograph for Tryngolza to address the identified safety concerns.

This New Drug Submission complies with the requirements of sections C.08.002 and C.08.005.1 and therefore Health Canada has issued the Notice of Compliance pursuant to section C.08.004 of the Food and Drug Regulations. For more information, refer to the Clinical, Non-clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.

The New Drug Submission for Tryngolza was subject to an expedited review process under the Priority Review of Drug Submissions Policy. The sponsor presented substantial evidence of clinical effectiveness to demonstrate that Tryngolza, in conjunction to diet, provides an effect treatment in reducing triglyceride levels in adult patients with familial chylomicronemia syndrome, a serious, life-threatening disease that is not adequately managed by a drug marketed in Canada.

The review of the New Drug Submission (NDS) for Tryngolza was based on a critical assessment of the data package submitted to Health Canada. The reviews completed by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) were used as added references for the review of the quality, non-clinical, and clinical components of the NDS, as per Method 3 described in the Draft Guidance Document: The Use of Foreign Reviews by Health Canada. The Canadian regulatory decision on the Tryngolza NDS was made independently based on the Canadian review.

As part of the NDS package, the submission included a pediatric development plan that had been provided to the European Medicines Agency (EMA) as part of Health Canada’s Pilot on pediatric development plans and studies.

For additional information about the drug submission process, refer to the Guidance Document: The Management of Drug Submissions and Applications.

Submission Milestones: Tryngolza

Requirements for post-market commitments are outlined in the Food and Drugs Act and Food and Drug Regulations.

Summary Basis of Decision documents (SBDs) for eligible drugs (as outlined in Frequently Asked Questions: Summary Basis of Decision [SBD] Project: Phase II) authorized after September 1, 2012 will include post-authorization information in a table format. The Post-Authorization Activity Table (PAAT) will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada’s decisions were negative or positive. The PAAT will continue to be updated during the product life cycle.

At this time, no PAAT is available for Tryngolza. When available, the PAAT will be incorporated into this SBD.

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Refer to the What steps led to the approval of Tryngolza? section for more information about the review process for this submission.