Apellis and Sobi Report Positive Top-line Results at 48 Weeks from the Phase 3 PEGASUS Study of Pegcetacoplan in PNH

Rhea-AI Summary

Apellis Pharmaceuticals and Sobi announced positive results from the Phase 3 PEGASUS study on pegcetacoplan for paroxysmal nocturnal hemoglobinuria (PNH), showing a mean hemoglobin increase of 2.7 g/dL at Week 48. 73% of pegcetacoplan-treated patients were transfusion-free. The treatment's safety profile was consistent with previous results, with no new safety signals. pegcetacoplan is under review by the FDA and EMA, with a target action date of May 14, 2021 for FDA. This study highlights pegcetacoplan's potential to improve the lives of patients suffering from PNH.

Positive

• Mean hemoglobin increase of 2.7 g/dL at Week 48 sustained from Week 16.
• 73% of patients treated with pegcetacoplan remained transfusion-free.
• Consistent safety profile with no new safety signals identified.

Negative

• 30% of pegcetacoplan patients experienced serious adverse events, with 12% discontinuing treatment due to adverse effects.

• Treatment with pegcetacoplan resulted in a sustained improvement in hemoglobin with a mean increase from baseline of 2.7 g/dL at Week 48, which is equal to the 2.7 g/dL increase seen at Week 16 with pegcetacoplan-treated patients

• Sustained improvements in transfusion avoidance, reticulocyte count, lactate dehydrogenase (LDH) level, and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score were observed in patients treated with pegcetacoplan

• Safety profile of pegcetacoplan was consistent with previously reported data
  

WALTHAM, Mass. and STOCKHOLM, Sweden, Dec. 10, 2020 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) and Sobi™ Swedish Orphan Biovitrum AB (publ) (Sobi™) (STO:SOBI) today announced positive top-line results at Week 48 from the Phase 3 PEGASUS study, which demonstrated sustained hematological and clinical improvements in patients with paroxysmal nocturnal hemoglobinuria (PNH) who were treated with pegcetacoplan, an investigational, targeted C3 therapy. The safety profile of pegcetacoplan was consistent with previously reported data, and no new safety signals were identified.

All patients (n=77) who completed the 16-week randomized controlled period of the PEGASUS study, which evaluated pegcetacoplan compared to eculizumab, entered the open-label period and received pegcetacoplan from Week 17 to Week 48.

At Week 48, hemoglobin increases were sustained in pegcetacoplan-treated patients with a mean improvement from baseline of 2.7 g/dL, which is equal to the 2.7 g/dL mean increase seen at Week 16 with pegcetacoplan-treated patients. Additionally, eculizumab-treated patients who switched to pegcetacoplan during the open-label period experienced sustained improvements in hemoglobin and other hematological and clinical measures, similar to patients treated with pegcetacoplan monotherapy during the randomized controlled period.

“These long-term results show that pegcetacoplan has the potential to help patients with PNH gain and maintain more complete control of the disease,” said Federico Grossi, M.D., Ph.D., chief medical officer of Apellis. “The sustained hematologic and quality-of-life improvements and consistent safety profile of pegcetacoplan observed in this study adds to a growing body of evidence that demonstrates the potential of this investigational, targeted C3 therapy to elevate the standard of care and improve the lives of people with PNH.”

In addition to a sustained improvement in hemoglobin, patients treated with pegcetacoplan maintained improvements across key secondary endpoints. Throughout the 48-week study, 73% of patients treated with pegcetacoplan remained transfusion free. For comparison, 25% of patients were transfusion free over the year prior to entering the PEGASUS study while on treatment with eculizumab. Improvements across additional markers of disease, such as reticulocyte count, lactate dehydrogenase (LDH) levels, and the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scores, were maintained.

Overall, the safety profile of pegcetacoplan was consistent with previously reported data throughout the 48-week study. Twenty-four of 80 pegcetacoplan monotherapy-treated patients (30%) experienced a serious adverse event (SAE); five of the SAEs (6%) were assessed to be possibly related to study treatment. No cases of meningitis were reported. One death was reported due to COVID-19 and was unrelated to study treatment. The most common adverse events (AEs) reported throughout the study were injection site reactions (36%), hemolysis (24%), and diarrhea (21%). Twelve out of 80 patients (15%) discontinued due to adverse events, with five discontinuations due to hemolysis. Sixty-four of the 67 patients (96%) who completed the open-label period opted to enter the extension study.

“Despite existing treatments, many patients with PNH continue to suffer from persistently low hemoglobin, which can lead to a need for frequent transfusions and debilitating fatigue,” said Ravi Rao, head of R&D and chief medical officer at Sobi. “The long-term data suggest that pegcetacoplan, if approved, has the potential to provide meaningful and durable benefits to these patients with high unmet medical need.”

Marketing applications for pegcetacoplan for the treatment of PNH are under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA granted the application Priority Review designation and set a target action date of May 14, 2021. An opinion from the Committee for Medicinal Products for Human Use (CHMP) is expected in 2021.

Detailed data will be presented at a future medical congress.

About the PEGASUS Study
The PEGASUS study (APL2-302; NCT03500549) is a multi-center, randomized, head-to-head Phase 3 study in 80 adults with paroxysmal nocturnal hemoglobinuria (PNH). The primary objective of this study was to establish the efficacy and safety of pegcetacoplan compared to eculizumab. Participants must have been on eculizumab (stable for at least three months) with a hemoglobin level of <10.5 g/dL at the screening visit. During the four-week run-in, patients were dosed with 1080 mg of pegcetacoplan twice weekly (n=41) in addition to their current dose of eculizumab. During the 16-week randomized, controlled period, patients were randomized to receive either 1080 mg of pegcetacoplan twice weekly or their current dose of eculizumab (n=39). All participants completing the randomized controlled period (n=77) opted to enter the open-label pegcetacoplan treatment period.

About Pegcetacoplan
Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b. Pegcetacoplan is being evaluated in several clinical studies across hematology, ophthalmology, nephrology, and neurology. Marketing applications for pegcetacoplan for paroxysmal nocturnal hemoglobinuria (PNH) are under review by the U.S. Food and Drug Administration (FDA), which has granted the application Priority Review designation, and the European Medicines Agency (EMA). Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of geographic atrophy, and received orphan drug designation for the treatment of C3G by the FDA and European Medicines Agency. For additional information regarding pegcetacoplan clinical trials, visit https://apellis.com/our-science/clinical-trials.

About Paroxysmal Nocturnal Hemoglobinuria (PNH) 
PNH is a rare, chronic, life-threatening blood disorder characterized by the destruction of oxygen-carrying red blood cells through extravascular and intravascular hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue, hemoglobinuria and difficulty breathing (dyspnea). A retrospective analysis shows that, even on eculizumab, approximately 72% of people with PNH have anemia, a key indicator of ongoing hemolysis.¹ The analysis also finds that 36% of patients require one or more transfusions a year and 16% require three or more.¹

About Apellis 
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop transformative therapies for a broad range of debilitating diseases that are driven by excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology. For more information, please visit http://apellis.com.

About Sobi
Sobi is a specialized international biopharmaceutical company transforming the lives of people with rare diseases. Sobi is providing sustainable access to innovative therapies in the areas of hematology, immunology and specialty indications. Today, Sobi employs approximately 1,500 people across Europe, North America, the Middle East, Russia and North Africa. In 2019, Sobi's revenue amounted to SEK 14.2 billion. Sobi's share (STO:SOBI) is listed on Nasdaq Stockholm. You can find more information about Sobi at www.sobi.com.

Apellis Forward-Looking Statement 
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the implications of preliminary clinical data. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether the company’s clinical trials will be fully enrolled and completed when anticipated; whether preliminary or interim results from a clinical trial will be predictive of the final results of the trial; whether results obtained in preclinical studies and clinical trials will be indicative of results that will be generated in future clinical trials; whether pegcetacoplan will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of the company’s clinical trials will warrant regulatory submissions and whether pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for GA, PNH, CAD, C3G, IC-MPGN, ALS or any other indication when expected or at all; whether, if Apellis’ products receive approval, they will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 2, 2020 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts:

Apellis
Media:
Lissa Pavluk 
media@apellis.com 
617.977.6764

Investors: 
Argot Partners
apellis@argotpartners.com
+1 212.600.1902

Sobi
Paula Treutiger, Head of Communication & Investor Relations
+ 46 733 666 599
paula.treutiger@sobi.com

Linda Holmström, Corporate Communication & Investor Relations
+ 46 708 734 095
linda.holmstrom@sobi.com

1. McKinley C. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130:3471.

FAQ

What results were observed in the PEGASUS study for pegcetacoplan?

The PEGASUS study reported a sustained mean hemoglobin increase of 2.7 g/dL after 48 weeks of treatment with pegcetacoplan.

How many patients remained transfusion-free while using pegcetacoplan?

73% of pegcetacoplan-treated patients were transfusion-free at the end of the PEGASUS study.

What is the safety profile of pegcetacoplan based on the PEGASUS study?

The safety profile of pegcetacoplan was consistent with previously reported data, with no new safety signals detected.

What is the target action date for pegcetacoplan's FDA review?

The FDA has set a target action date of May 14, 2021, for pegcetacoplan's marketing application.