With extensive research into both olezarsen and plozasiran available within our Third Bridge Library, you can find key insights from relevant interviews to kickstart your research below.
Arrowhead Pharmaceuticals – Anti-APOC3's Face-off in FCS & Read-through to SHTG Market Dynamics
Transcript key insights:
- Ionis’ olezarsen’s antisense oligonucleotide mechanism may increase risk of cumulative toxicity. siRNAs are generally considered to have cleaner safety profiles. Specialist anticipates plozasiran could capture 40-50% market share in FCS, with favourable dosing frequency playing a major role.
- In sHTG, treatment goals differ from FCS, focusing on both pancreatitis prevention and long-term cardiovascular risk reduction, particularly in secondary prevention settings.
- Specialist expects olezarsen to achieve 45-55% triglyceride reduction in sHTG trials, with potential variability based on patient subgroups and metabolic factors. 5-10% absolute difference in triglyceride reduction between olezarsen and plozasiran could be both statistically and clinically meaningful, particularly for patients with very high baseline triglycerides.
- Pancreatitis risk reduction may be difficult to prove in sHTG due to lower baseline rates of incidence.
- APOC3 inhibitors could hold up to 80% market share in sHTG treatment paradigm in five years, with AI-based risk modeling and genetic screening playing a larger role.
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Ionis Pharmaceuticals – Olezarsen's Competitive Sustainability & Label Expansion Outlook
Transcript key insights:
- Olezarsen has been difficult to procure, although Ionis's high-touch services stand out. Specialist is very impressed by 50% reduction in 2,000mg-per-decilitre triglycerides after one dose in FCS patient.
- If 60% triglyceride reduction continues, specialist plans to use olezarsen first-line for patients with >1,000mg-per-decilitre triglycerides or recurrent pancreatitis, and third- or fourth-line initially for sHTG patients stuck around 600-900mg per decilitre after statins, fibrates and Vascepa. Off-label use is likely before sHTG approval.
- SHTG patients with cardiac event history or low-density lipoprotein ≥70-100mg will initially be excluded from specialist's prescribing, due to paradoxical low-density-lipoprotein increase associated with olezarsen.
- Widespread use of obesity medications could significantly impact triglyceride levels and metabolic profiles, potentially affecting forecasting models for triglyceride-lowering drugs including Tryngolza.
- Concerns about plozasiran's effect on platelet count and its quarterly dosing's long-lasting nature makes specialist sceptical of its success, also noting importance of first-mover advantage.
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Lipid Disorder Treatment Market – Competitive Landscape & Advancing Therapeutic Innovation – Part 1
Transcript key insights:
- PCSK9 inhibitors, introduced in 2015, effectively lower LDL-C by 50-60% but are underutilised. Oral PCSK9 inhibitors, such as MK-0616 and AZD0780, will likely increase market penetration by overcoming resistance to injectable administration and offering improved combination therapies with other oral medications.
- CETP inhibitor obicetrapib shows promise in lowering LDL-C by 35% and Lp(a) by 50%, differentiating it from previous failed CETP inhibitors. BROADWAY trial for obicetrapib demonstrated a 1% delta in four-point major adverse cardiovascular events, suggesting potential cardiovascular risk reduction in future outcomes trials.
- Specialist thinks payer authorisation, formulary inclusion and out-of-pocket costs will significantly influence the choice between emerging oral LDL-lowering therapies.
- "Despite the fact that we have guidelines […] [w]e do have large percentages of treatment gaps, and we see nationally large under-measurement of LDL cholesterol and lipid panels". As such, new and innovative therapies are presented with a meaningful market.
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Lipid Disorder Treatment Market – Competitive Landscape & Advancing Therapeutic Innovation – Part 2
Transcript key insights:
- VERVE-102, a novel base editing therapy, showed promising results in lowering LDL-C by up to 53% in early trials, rivaling PCSK9 inhibitors while potentially requiring fewer doses. VERVE-102 may not eliminate the need for all LDL-lowering agents, given patients might still require statins and ezetimibe.
- VERVE-201, targeting ANGPTL3, aims to reduce LDL-C and remnant cholesterol levels through a distinct mechanism, potentially benefiting patients with homozygous familial hypercholesterolaemia and refractory hypercholesterolaemia.
- CRISPR Therapeutics' CTX-320 shows potential for lowering Lp(a) levels by up to 90% from baseline, addressing a significant unmet need in cardiovascular risk reduction.
- Ionis Pharma's Tryngolza, approved in December 2024, is the first treatment for adults with FCS, targeting APOC3 to lower triglycerides and reduce pancreatitis risk.
- Arrowhead Pharma's plozasiran, an APOC3 inhibitor with a longer duration of action, demonstrated significant triglyceride reduction and pancreatitis prevention in the PALISADE trial.
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Ionis Pharmaceuticals – Tryngolza Post-approval Dynamics & SHTG Read-out Expectations
Transcript key insights:
- Specialist views Ionis's olezarsen and Arrowhead’s plozasiran efficacy and safety as essentially equal, with first-to-market, dosing, administration and payer acceptance as key market share drivers.
- The sHTG population is larger but more heterogeneous than that of FCS, potentially limiting widespread use of apolipoprotein C-III inhibitors due to varying patient needs and response to existing therapies. Success in FCS may not directly translate to sHTG, as payers may require stronger evidence of pancreatitis reduction and cost-effectiveness for broader adoption.
- Apolipoprotein C-III inhibitors are positioned as third-line therapy after lifestyle changes, fibrates and omega-3s, potentially limiting market penetration in non-FCS sHTG patients.
- "I fully anticipate […] the payer community to sort of demand a cardiovascular outcomes trial to fully ensconce a therapy like these therapies into the mild-to-moderate hypertriglyceridemia, mixed dyslipidemia group".
- Undiagnosed sHTG cases, particularly in patients with obesity and diabetes, represent a potential untapped market for new triglyceride-lowering therapies.
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Arrowhead Pharmaceuticals – Path to Plozasiran FCS Approval & SHTG Development Outlook
Transcript key insights:
- Specialist is impressed with 80%-plus triglyceride reduction in FCS patients in PALISADE study, noting that it "would be practice-changing" to have pancreatitis reduction. Olezarsen appears more dose-dependent than plozasiran. However, specialist believes plozasiran still appears more effective at reducing APOC3 and triglycerides.
- Specialist believes that if Arrowhead secures broader FCS label, market would broaden and ease payment concerns, but this would create complications in orphan designation. Specialist expects FDA to ask for data delineating genetically confirmed and non-confirmed subgroups.
- Given the similarity in FCS data, specialist thinks first-mover advantage for Ionis could be overcome if plozasiran establishes sustained efficacy and maintains its quarterly dosing advantage.
- Cardiovascular outcome trials for mixed hyperlipidemia should aim for at least 15% relative risk reduction, with 20%-plus being ideal for commercial success. However, lack of efficacy in cardiovascular risk reduction wouldn't jeopardise FCS and SHTG markets, as the primary goal is pancreatitis reduction.
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