Executive Summary / Key Takeaways

• Amicus Therapeutics is transforming into a profitable rare disease leader, driven by the robust commercial performance of its two precision medicines, Galafold for Fabry disease and Pombiliti + Opfolda for Pompe disease, targeting a combined $1 billion in sales by 2028.
• The company achieved GAAP profitability in Q3 2025, marking a significant financial inflection point, supported by strong revenue growth (Q3 2025 total revenue up 17% at constant exchange rates) and disciplined operational management.
• Strategic pipeline expansion with DMX-200, a Phase 3 asset for Focal Segmental Glomerulosclerosis (FSGS), introduces a potential blockbuster in rare kidney disease, leveraging Amicus's existing commercial infrastructure and differentiated mechanism of action.
• Amicus maintains a strong competitive position through its proprietary oral and two-component enzyme stabilization technologies, which offer tangible patient benefits and drive high adherence rates, while proactively managing supply chain risks and intellectual property.
• Key catalysts include continued geographic expansion for Pombiliti + Opfolda, potential label expansions for pediatric Pompe patients, and the progression of the DMX-200 Phase 3 study, with an FDA meeting anticipated in Q1 2026 for interim analysis.

Amicus Therapeutics: A Decade of Dedication to Rare Disease Innovation

Amicus Therapeutics, Inc. has evolved from its 2002 inception into a global, patient-dedicated biotechnology company, steadfastly focused on discovering, developing, and delivering novel medicines for rare diseases. The company's foundational strategy centers on bringing first- or best-in-class therapies to market, a commitment that has shaped its current portfolio and strategic direction. This journey has been characterized by significant investment in research and development, alongside the meticulous establishment of a global commercial infrastructure.

The rare disease market itself presents a compelling landscape, marked by a growing diagnosed patient population and an increasing appreciation for earlier intervention. Conditions like Fabry and Pompe disease, Amicus's core therapeutic areas, continue to reveal larger undiagnosed populations than historically estimated, underscoring a substantial and expanding market opportunity.

In this specialized arena, Amicus positions itself as an agile innovator, competing directly with larger pharmaceutical entities like Sanofi (SNY) and specialized biotechs such as BioMarin Pharmaceutical Inc. (BMRN) and PTC Therapeutics Inc. (PTCT). While larger competitors may boast broader portfolios and greater scale, Amicus differentiates itself through a focused approach on precision medicines and unique technological platforms. This targeted strategy allows Amicus to effectively address niche patient needs and potentially achieve greater market penetration in its specific therapeutic segments.

Technological Edge: Precision Medicines Driving Differentiation

Amicus's competitive moat is significantly strengthened by its proprietary technologies, which offer distinct advantages in the treatment of rare genetic disorders.

Galafold: Oral Precision for Fabry Disease

Galafold (migalastat) stands as the first oral monotherapy for Fabry disease patients with amenable genetic variants. Its core technology involves a small molecule designed to bind to and stabilize the endogenous alpha-galactosidase A (alpha-Gal A) enzyme. This oral administration provides a tangible benefit of convenience for patients, a critical factor in long-term adherence. The therapy has demonstrated high compliance and adherence rates, consistently exceeding 90%. In mature markets, Galafold has achieved impressive market shares, reaching between 85% and 90% of amenable Fabry patients, underscoring its positioning as the treatment of choice. This technological advantage translates directly into strong customer loyalty and recurring revenue streams, contributing to superior margins by potentially reducing administration costs and enhancing pricing power in its niche market.

Pombiliti + Opfolda: A Novel Two-Component Approach for Pompe Disease

For late-onset Pompe disease (LOPD), Amicus offers Pombiliti + Opfolda, a novel two-component treatment. This therapy combines cipaglucosidase alfa-atga, a uniquely engineered recombinant human acid alpha-glucosidase (rhGAA) enzyme, with orally administered miglustat. The cipaglucosidase alfa-atga is enriched with bis-M6P to enhance cellular uptake, while miglustat acts as an oral enzyme stabilizer, reducing inactivation of the rhGAA in circulation and improving the uptake of the active enzyme into key disease-relevant tissues.

The tangible benefits of this technology are supported by robust clinical data. Four-year data from the PROPEL open-label extension study demonstrated durable improvements or stability in key endpoints of muscle function, muscle strength, and biomarkers in ERT-experienced patients. Notably, Pombiliti + Opfolda is the only product in a controlled study to show improvement for patients switching from prior enzyme replacement therapy (ERT). This differentiation is critical in a competitive landscape that includes other ERTs like Sanofi's Nexviazyme and Lumizyme.

DMX-200: Targeting Inflammation in FSGS

Amicus's pipeline expansion with DMX-200 introduces a differentiated technological approach for Focal Segmental Glomerulosclerosis (FSGS), a rare kidney disease. DMX-200 is a small molecule inhibitor of the chemokine receptor 2 (CCR2). Its unique mechanism of action involves blocking the signaling from the A1TR CCR2 heteromer on damaged kidney cells, which leads to the degradation of monocyte chemoattractant protein-1 (MCP-1). This downstream blocking mechanism is distinct from traditional CCR2 inhibitors, which can lead to an MCP-1 rebound effect.

Phase 2 studies for DMX-200 showed robust reductions in proteinuria, particularly in patients with the highest MCP-1 and proteinuria levels. This targeted approach to monocyte-driven inflammation is unique among clinical-stage kidney disease programs, offering a strategic advantage over other late-stage agents targeting alternative pathways, such as endothelin receptor antagonists and APOL1 inhibitors. The "so what" for investors is clear: these technological differentiators provide Amicus with a strong competitive edge, enabling it to command premium pricing, achieve high market penetration in niche segments, and drive long-term revenue growth.

Galafold: A Foundation of Sustained Growth

Galafold continues to be a cornerstone of Amicus's commercial success, demonstrating consistent growth and market leadership in Fabry disease. For the three months ended September 30, 2025, Galafold generated net product sales of $138.3 million, representing a 12% increase at constant exchange rates (CER) over the prior year period. Year-to-date through September 30, 2025, Galafold sales reached $371.5 million. The full year 2024 saw Galafold revenue hit $458.1 million, growing 19% at CER.

This robust performance is driven by strong patient demand, with Q3 2025 marking the strongest quarter ever for new commercial demand for Galafold. The company reported 13% year-over-year patient growth in Q3 2025, fueled by record new patient starts. Approximately 69% of the global market share of treated Fabry patients with amenable mutations are now on Galafold. The global patient mix is shifting, with 65% naive and 35% switch patients, indicating a stronger uptake in newly diagnosed populations.

The Fabry market itself is expanding, with diagnosed patients growing from approximately 10,000 worldwide in 2016 to 18,000 by 2024. The untreated population also increased from 5,000 to 6,000 during the same period, highlighting a significant opportunity for further penetration. Amicus's intellectual property for Galafold is well-protected, with a settlement reached with Teva (TEVA) in October 2024 allowing generic entry no earlier than January 30, 2037. Litigation with Aurobindo Pharma Limited (ARBPY) is ongoing, with a trial held in September 2025 and post-trial briefings concluding by December 2025. For 2025, Amicus projects Galafold revenue growth of 10% to 15% at CER, reinforcing its path to surpassing $1 billion in peak sales.

Pombiliti + Opfolda: Accelerating Momentum in Pompe Disease

Pombiliti + Opfolda is rapidly gaining traction as a significant growth driver for Amicus, challenging existing therapeutic paradigms in Pompe disease. The product generated $30.7 million in net product sales for the three months ended September 30, 2025, a 42% increase at CER. Year-to-date through September 30, 2025, sales reached $77.5 million, growing 59% at CER. The full year 2024 saw Pombiliti + Opfolda revenue exceed $70 million.

Q3 2025 marked the strongest quarter ever for new commercial demand for Pombiliti + Opfolda, demonstrating significant momentum in both established and newly launched markets. The number of patients switching from avalglucosidase alfa (Sanofi's Nexviazyme) to Pombiliti + Opfolda doubled in the first nine months of 2025 compared to all of 2024, with naive prescriptions ex-U.S. also doubling in the same period. In the U.S., approximately 68% of patients switching to Pombiliti + Opfolda are coming from Nexviazyme. The U.S. insurance process has become more efficient, with time to reimbursement dropping to under 30 days.

Amicus has secured reimbursement for Pombiliti + Opfolda in 15 countries as of Q3 2025, with key new markets like Japan, Belgium, Ireland, and Luxembourg recently added. Countries launched in Q2 2025, including Switzerland, Italy, the Czech Republic, Portugal, and the Netherlands, began generating revenue in Q3 2025. The Netherlands, a significant Pompe market, is expected to see approximately 70% of its patients switch to Pombiliti + Opfolda, providing a substantial growth driver.

The company aims for Pombiliti + Opfolda to become the new standard of care, targeting over 50% market share at peak and over $1 billion in peak sales potential. This ambition is supported by ongoing label expansion efforts for pediatric late-onset Pompe disease (adolescent patients by mid-2026, younger LOPD patients by 2027) and infantile-onset Pompe disease (following the younger LOPD group). The competitive landscape shows a notable contrast, with Sanofi's global Pompe franchise experiencing a 5% decline in Q1 2025, while Amicus's Pombiliti + Opfolda demonstrated 90% growth in the same period.

DMX-200: Expanding the Pipeline into Rare Kidney Disease

Amicus's strategic in-licensing of DMX-200 on April 30, 2025, marks a significant expansion into the rare kidney disease space, leveraging its established commercial and regulatory infrastructure. The agreement with Dimerix Bioscience Pty Limited grants Amicus exclusive U.S. commercialization rights for DMX-200, a Phase 3 drug candidate for Focal Segmental Glomerulosclerosis (FSGS) and other indications. The deal structure, involving a $30 million upfront payment and substantial success-based milestones (up to $75 million for FSGS development/regulatory, $40 million for other indications, and $445 million for commercial milestones), along with tiered royalties, aligns with Amicus's focus on de-risked, late-stage assets.

FSGS represents a high unmet medical need, affecting over 40,000 people in the U.S. with approximately 5,000 new cases diagnosed annually. The disease is characterized by progressive scarring, proteinuria, and kidney function loss, often leading to end-stage kidney disease within five years for progressive cases. DMX-200's differentiated mechanism, specifically targeting monocyte-driven inflammation, sets it apart from other therapies in development.

The pivotal Phase 3 ACTION3 study for DMX-200 is progressing well, with over 90% of patients enrolled and on track for full enrollment by the end of 2025. Crucially, the FDA has aligned on proteinuria as an appropriate primary endpoint for traditional marketing approval. Amicus anticipates requesting an additional meeting with the FDA in Q1 2026 to discuss the next interim analysis and further development steps. This asset is considered a potential blockbuster, strategically enhancing Amicus's long-term growth trajectory.

Financial Strength and Operational Discipline

Amicus Therapeutics has reached a significant financial inflection point, achieving GAAP profitability in Q3 2025, with a net income of $17.3 million ($0.06 per share). This marks the company's first quarter of positive GAAP net income in 2025, aligning with its guidance for profitability in the second half of the year. Non-GAAP net income for Q3 2025 was $54.2 million ($0.18 per share), a notable increase from $30.8 million ($0.10 per share) in Q3 2024.

The company's financial health is further underscored by its liquidity position. As of September 30, 2025, cash, cash equivalents, and marketable securities totaled $263.8 million, representing a $32.8 million increase during Q3 2025. Net cash provided by operating activities for the nine months ended September 30, 2025, was $16.9 million, demonstrating positive operational cash generation. Amicus believes its current cash position is sufficient to fund operations and ongoing research programs for at least the next 12 months.

While operating expenses have seen increases, they are largely tied to strategic growth initiatives. Research and development costs increased by $32.9 million for the nine months ended September 30, 2025, primarily due to the $30 million upfront license payment for DMX-200. Selling, general, and administrative expenses rose by $29.7 million over the same period, driven by higher professional fees for legal efforts, increased personnel costs to support product supply, and expansion of manufacturing capabilities.

Amicus has provided full-year 2025 guidance, projecting total revenue growth of 15% to 22% at CER, with Galafold growing 10% to 15% at CER and Pombiliti + Opfolda growing 50% to 65% at CER. Gross margin is expected to be in the mid-80s, likely at the top end of the 83% to 87% range. Non-GAAP operating expense is guided to be at the high end of the $380 million to $400 million range. The company has also proactively managed its supply chain, diversifying manufacturing to Ireland and initiating U.S. drug product manufacturing for Pombiliti + Opfolda to mitigate potential tariff impacts, anticipating "very little exposure" in 2025 and 2026.

Risks and Challenges

Despite its strong trajectory, Amicus faces several inherent risks. Intellectual property litigation, such as the ongoing case with Aurobindo regarding Galafold, poses a potential threat, though the company remains confident in its IP strength. Regulatory approvals and reimbursement timelines, particularly for new markets and label expansions, can be unpredictable. The competitive landscape, with established players and emerging therapies in both Fabry and Pompe diseases, as well as new entrants in FSGS, necessitates continuous innovation and differentiation. Fluctuations in foreign currency exchange rates also present a risk, given a significant portion of revenue is generated outside the U.S., although a weakening dollar generally provides a favorable impact.

Conclusion

Amicus Therapeutics stands at a pivotal juncture, successfully transitioning to GAAP profitability while executing a clear strategy for sustained growth. The company's core investment thesis is underpinned by the proven commercial strength of Galafold and the accelerating momentum of Pombiliti + Opfolda, both precision medicines that address significant unmet needs in rare diseases. The strategic addition of DMX-200 to its pipeline further diversifies its growth drivers, positioning Amicus to leverage its global infrastructure in the promising rare kidney disease market.

With a robust technological foundation, a disciplined financial approach, and a clear roadmap for market expansion and label extensions, Amicus is well-positioned to achieve its ambitious goal of $1 billion in combined product sales by 2028. While competitive pressures and regulatory complexities remain, the company's focus on differentiated therapies and operational efficiency suggests a compelling long-term value proposition for investors seeking exposure to a growing leader in the rare disease biotechnology sector.