Apellis Pharmaceuticals (APLS) Q3 2025: Empaveli Launch Drives 152 Patient Starts, Sets Stage for Nephrology Ramp
Apellis’s Q3 2025 marked a pivotal launch phase for Empaveli, with 152 patient start forms reflecting early traction in rare kidney diseases and a broad label reach. Cyfovre’s steady 4% injection growth was tempered by persistent free goods headwinds, highlighting both the market’s undertreatment and reimbursement friction. Management’s focus on education, new delivery tools, and pipeline expansion signals a multi-year push to reinvigorate adoption and extend leadership in complement science.
Summary
- Empaveli Launch Momentum: Early nephrology adoption is translating into real-world patient starts and prescriber engagement.
- Cyfovre Growth Constraints: Free goods and access challenges continue to weigh on reported revenue despite demand signals.
- Strategic Pipeline Expansion: New pivotal trials in rare kidney diseases and delivery innovation aim to unlock future revenue streams.
Performance Analysis
Apellis delivered total Q3 revenue of $459 million, buoyed by a $275 million upfront from the SOBI royalty transaction, but underlying product dynamics were mixed. Cyfovre, the company’s flagship C3 inhibitor for geographic atrophy (GA), generated $151 million in net product revenue, with approximately 101,000 doses delivered—yet a significant portion (15,000) were free goods, resulting in a $15 million revenue headwind and continuing a trend that has now reached $40 million year-to-date. The sequential 4% injection growth was driven predominantly by these non-revenue doses, pointing to both demand and ongoing access bottlenecks.
Empaveli, targeting PNH and newly approved for C3G and ICMPGN, posted $27 million in net product revenue across indications. The launch into nephrology is progressing, with 152 patient start forms received by quarter’s end—about one-third from expanded access program (EAP) conversions and the remainder representing new commercial demand. Operating expenses were tightly managed at $235 million, down year-over-year, and the company ended with $475 million in cash, aided by the SOBI deal and a shift away from receivables factoring, which is expected to yield $5 million in annual cost savings.
- Empaveli Start Forms Signal Launch Execution: 152 start forms, spanning the full breadth of the label, reflect both prescriber buy-in and early patient identification success.
- Free Goods Dilute Cyfovre Revenue: Elevated free drug usage, above prior expectations, continues to suppress reported sales despite underlying injection growth.
- Gross-to-Net Pressures Persist: Gross-to-net adjustments for Cyfovre trended above the low-to-mid 20% range, highlighting payer and access friction in the buy-and-bill channel.
Looking ahead, management expects Q4 Cyfovre revenue to be broadly in line with Q3, with only modest injection growth anticipated and no near-term resolution to patient assistance funding constraints. The Empaveli launch is expected to transition from the initial bolus of EAP and early adopters to a steadier, gradual ramp as payer policies and prescriber education mature.
Executive Commentary
"A key milestone was the FDA approval of Empaveli for the treatment of patients 12 years and older with C3 glomerulopathy or primary immune complex membranoproliferative glomerulonephritis... This approval expands the addressable market for Empaveli by approximately 5,000 patients and marks a breakthrough therapy that delivers meaningful results across the trifecta of key disease control measures."
Dr. Cedric Francois, Co-founder and Chief Executive Officer
"We delivered approximately 101,000 doses of Cyfovre in the quarter, including 86,000 commercial doses and 15,000 free goods doses. In line with our expectations, we saw 4% sequential growth in overall total injection demand during the third quarter, driven predominantly by free goods. While we are encouraged by the continued growth in total injections as a leading indicator of demand, we did see an approximate $15 million headwind to our reported revenue due to the elevated use of free goods, which was slightly higher than our expectations."
Tim Sullivan, Chief Financial Officer
Strategic Positioning
1. Empaveli’s Broad Label and First-Mover Advantage
Empaveli’s FDA approval in C3G and ICMPGN positions Apellis as the only company with a C3 inhibitor across a comprehensive range of nephrology indications, including pediatric and post-transplant populations. This broad label, coupled with positive efficacy data (proteinuria reduction, eGFR stabilization, C3 clearance), enables penetration into a market of roughly 5,000 patients—two-thirds of whom have no alternative therapy. Early prescriber feedback is positive, and the on-body auto-injector delivery offers a differentiator versus oral competitors, but the real test will be sustaining adoption beyond early EAP conversions.
2. Cyfovre: Market Leadership Amidst Access and Adoption Friction
Cyfovre remains the market leader in GA, accounting for an estimated 52% of new patient starts and over 60% of the overall market, but only about 10% of diagnosed patients are being treated with complement inhibitors. The undertreatment is driven by both physician inertia (“wait-and-see” approach) and patient access challenges, with copay assistance limitations and free drug programs distorting revenue capture. Management’s near-term focus is on education, targeting early-career retina specialists and developing AI tools to visualize disease progression, aiming to reaccelerate adoption over the next 12 to 18 months.
3. Pipeline Expansion to Rare Kidney Diseases
Apellis is leveraging its C3 platform to expand into additional rare nephrology indications, with pivotal trials in primary focal segmental glomerulosclerosis (FSGS, ~13,000 US patients) and delayed graft function (DGF, ~21,000 kidney transplants annually) set to initiate by year-end. These segments lack FDA-approved therapies and represent significant future market opportunities, reinforcing Apellis’s strategy of targeting high-need, low-competition areas where complement dysregulation is central.
4. Delivery Innovation as a Growth Catalyst
The development of a pre-filled syringe for Cyfovre is a key operational priority, expected to improve practice workflow and lower barriers for retina specialists—especially those who have not yet adopted the therapy. While timelines remain undisclosed, management emphasized high physician enthusiasm and the expectation that this will both deepen share with current prescribers and expand the overall treated population.
5. Commercial Discipline and Cash Preservation
Operating expenses were down year-over-year, and the SOBI royalty deal provided a $275 million cash infusion, enabling Apellis to discontinue costly receivables factoring. Management expects current cash reserves to fund the business to sustainable profitability, emphasizing disciplined investment in commercialization and pipeline advancement.
Key Considerations
This quarter underscores Apellis’s transition from foundational innovation to commercial scale, with execution challenges and opportunities defining the next phase.
Key Considerations:
- Empaveli Launch Trajectory: Sustained growth will depend on payer policy evolution, prescriber education, and conversion of EAP patients to commercial drug.
- Cyfovre Revenue Visibility: Free goods and patient assistance headwinds may persist, limiting near-term revenue upside despite demand signals.
- Physician Behavior Change: Market education and new delivery formats are required to shift retina specialists from a “wait-and-see” stance to proactive treatment.
- Pipeline Execution Risk: New pivotal trials in FSGS and DGF must overcome enrollment and clinical hurdles to deliver future growth.
- Cash Management: Cost discipline and cash preservation remain critical as Apellis invests in commercialization and pipeline expansion.
Risks
Access friction, including copay assistance gaps and payer delays, continues to constrain both Cyfovre and Empaveli ramp, with free drug usage diluting reported revenue. Physician inertia in GA, coupled with low overall treatment rates, creates uncertainty around the timeline for market expansion. Pipeline risks include clinical trial execution in new nephrology indications and the need for sustained differentiation versus emerging competitors. Apellis remains exposed to regulatory and reimbursement shifts, especially as it seeks to broaden adoption in underpenetrated markets.
Forward Outlook
For Q4 2025, Apellis guided to:
- Cyfovre revenue broadly in line with Q3, with low to mid-single digit injection growth.
- Empaveli launch metrics to reach at least 225 cumulative start forms by year-end.
For full-year 2025, management maintained guidance:
- Operating expenses in line with 2024 levels.
Management highlighted factors such as:
- Continued patient access challenges and elevated free goods as near-term revenue headwinds.
- Ongoing investments in physician education, delivery innovation, and pipeline trials as levers to drive future growth.
Takeaways
Apellis’s Q3 marks a critical inflection in commercial execution, as Empaveli’s nephrology launch builds momentum and Cyfovre’s market position is challenged by persistent access and reimbursement friction.
- Empaveli’s broad nephrology label is translating into early adoption, but a gradual ramp is expected as payer and operational hurdles are addressed.
- Cyfovre’s revenue remains pressured by free goods and assistance funding gaps, even as underlying demand signals opportunity for future growth.
- Investors should watch for updates on pre-filled syringe rollout, pipeline trial progress, and resolution of access headwinds as key drivers of medium-term upside.
Conclusion
Apellis’s Q3 2025 demonstrates both the promise and complexity of scaling a first-in-class complement platform, with early Empaveli launch momentum offset by persistent Cyfovre access challenges. The company’s multi-pronged strategy—spanning education, delivery innovation, and pipeline expansion—positions it for renewed growth, but execution risks and market inertia remain material watchpoints.
Industry Read-Through
Apellis’s experience highlights the dual challenge facing commercial-stage biotechs: even with differentiated products and broad labels, access friction and underdiagnosis can materially limit realized revenue in rare and specialty markets. The nephrology launch underscores the importance of pre-launch physician engagement and payer groundwork, while Cyfovre’s trajectory reflects the growing impact of patient assistance funding volatility across the biotech sector. Companies targeting underpenetrated specialty indications must invest in both delivery innovation and education to unlock full market potential, as clinical differentiation alone is insufficient to drive rapid adoption.