TRYNGOLZA's EU Approval Milestone and Market Potential for Sobi and Ionis: A Rare Disease Revolution

The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has delivered a landmark decision for Sobi and Ionis Pharmaceuticals: a positive opinion for TRYNGOLZA (olezarsen), an antisense therapy for familial chylomicronemia syndrome (FCS). This rare, genetic disorder affects fewer than 1 in 1 million individuals globally, yet its impact is devastating, with patients facing life-threatening acute pancreatitis episodes due to severe hypertriglyceridemia. The CHMP's endorsement marks a pivotal regulatory milestone, positioning TRYNGOLZA as a transformative treatment in the EU and reinforcing the strategic partnership between Sobi and Ionis in the rare disease and RNA therapeutics space.

Regulatory Breakthrough and Therapeutic Differentiation

TRYNGOLZA's mechanism of action is a game-changer. By targeting APOC3 mRNA, it reduces the production of apolipoprotein C-III, a protein that inhibits triglyceride clearance. Clinical trials, including the Phase 3 Balance study, demonstrated a 61% reduction in triglyceride levels after six months and a 100% reduction in acute pancreatitis events in the 80 mg dose group. These results not only outperform existing therapies but also address the root cause of FCS, rather than merely managing symptoms.

The CHMP's positive opinion, adopted in July 2025, follows a 13-month regulatory review initiated in August 2024. With the European Commission expected to finalize approval by Q4 2025, TRYNGOLZA will gain 10 years of orphan drug exclusivity—a critical advantage over competitors like Waylivra (volanesorsen), which faces patent expiration in the near term. This exclusivity, combined with TRYNGOLZA's superior safety profile (mild adverse effects like injection site reactions), cements its position as the first-line treatment for FCS in Europe.

Strategic Commercialization: Sobi's Role in Market Access

Sobi's partnership with Ionis is the linchpin of TRYNGOLZA's EU success. As the commercialization partner for Waylivra (the only existing FCS treatment in Europe), Sobi has deep expertise in navigating the complex reimbursement landscape for ultra-rare diseases. The company's operations span 30+ countries, including key markets like Germany, France, and the UK, where pricing and reimbursement decisions are often fragmented.

Under the 2025 licensing agreement, Sobi receives exclusive rights to commercialize TRYNGOLZA in the EU, leveraging its existing infrastructure to streamline patient access. This includes:
- Payer engagement: Sobi has already engaged with European payers to establish favorable reimbursement terms, mirroring the U.S. model where 90% of patients on TRYNGOLZA face zero out-of-pocket costs via the Ionis Every Step Support program.
- Disease education: Given FCS's high misdiagnosis rate, Sobi and Ionis are investing in physician training and patient advocacy to expand the diagnosed population.
- Supply chain optimization: Sobi's experience with Waylivra ensures a robust distribution network, critical for an antisense therapy requiring cold-chain logistics.

Financial terms of the partnership include upfront payments, milestone-based fees, and a mid-20% royalty on net sales—a structure that aligns Sobi's and Ionis' long-term incentives. With U.S. net sales of TRYNGOLZA exceeding $6 million in Q1 2025, the EU market could become a significant revenue driver, particularly as Sobi scales commercial operations.

Competitive Landscape and Long-Term Investment Potential

The FCS market in the EU is currently valued at $15 million for the 7MM, but this is set to expand as TRYNGOLZA displaces older therapies like GLYBERA (a gene therapy withdrawn due to cost inefficiency) and Waylivra. The latter's limited commercial success (despite NICE approval in the UK) underscores the challenges of pricing ultra-rare disease therapies. TRYNGOLZA's clinical superiority and Sobi's reimbursement expertise position it to capture a dominant market share.

Beyond FCS, Ionis is advancing olezarsen for severe hypertriglyceridemia (sHTG), a broader condition affecting 1–2 million Europeans. Phase 3 data from the CORE and ESSENCE trials (expected in Q3–Q4 2025) could unlock a $4.8 billion global market by 2033, with the EU contributing significantly. This dual-label strategy—targeting both rare and prevalent hypertriglyceridemic conditions—enhances TRYNGOLZA's long-term value proposition.

Investment Thesis: A Dual-Engine Growth Story

For investors, the Sobi-Ionis collaboration represents a dual-engine growth opportunity:
1. Orphan Drug Exclusivity: TRYNGOLZA's 10-year exclusivity in the EU insulates it from immediate competition, while the RNA therapeutics sector is projected to grow at a 25% CAGR through 2030.
2. Scalable Market Access: Sobi's proven ability to commercialize rare disease therapies (e.g., Waylivra's EU launch) reduces execution risk for TRYNGOLZA.
3. Pipeline Diversification: Ionis's sHTG trials could expand the patient base from ~2,000 FCS patients to 1–2 million in the EU alone, creating a durable revenue stream.

The partnership also benefits from favorable macro trends, including increasing payer willingness to reimburse high-cost therapies for ultra-rare diseases and advancements in RNA-based treatments. With TRYNGOLZA's EU approval imminent and sHTG data on the horizon, both Sobi and Ionis are positioned to deliver multiyear revenue growth and shareholder value.

Conclusion: A Rare Disease Revolution

TRYNGOLZA's CHMP approval is more than a regulatory win—it's a testament to the power of RNA therapeutics in addressing unmet medical needs. For Sobi and Ionis, this milestone validates their strategic focus on rare diseases and positions them to lead the next wave of innovation in metabolic disorders. Investors seeking exposure to high-conviction, long-duration growth should closely monitor the drug's EU launch and the broader pipeline. In a market where innovation often outpaces competition, TRYNGOLZA's success could redefine the standard of care for FCS—and redefine the fortunes of its developers.