Apellis and Sobi Report Positive Top-line Results from the Phase 3 PRINCE Study of EMPAVELI™ (pegcetacoplan) in Treatment-naïve Patients with PNH

Rhea-AI Summary

Apellis Pharmaceuticals (APLS) reported positive results from the Phase 3 PRINCE study of EMPAVELI™ (pegcetacoplan) for treating paroxysmal nocturnal hemoglobinuria (PNH) in treatment-naïve adults. The study showed statistical superiority in hemoglobin stabilization (86% vs. 0%, p<0.0001) and significant reduction in lactate dehydrogenase (90% decrease) compared to standard care. Mean hemoglobin levels rose from 9.4 to 12.1 g/dL in the EMPAVELI group. Additionally, 91% of EMPAVELI patients remained transfusion-free. The safety profile was consistent with previous studies, with serious adverse events being lower than standard care.

Positive

• EMPAVELI achieved 86% hemoglobin stabilization in treated patients.
• 90% reduction in lactate dehydrogenase levels from baseline.
• Mean hemoglobin increased from 9.4 g/dL to 12.1 g/dL in the EMPAVELI group.
• 91% of patients on EMPAVELI were transfusion-free.

Negative

• None.

• EMPAVELI demonstrated statistical superiority on the co-primary endpoints of hemoglobin stabilization (p<0.0001) and reduction in lactate dehydrogenase (LDH) (p<0.0001) compared to standard of care, which did not include complement inhibitors, at Week 26
  
  
• Mean hemoglobin levels in the EMPAVELI group increased from 9.4 g/dL to 12.1 g/dL compared to an increase from 8.7 g/dL to 9.4 g/dL on standard of care (p=0.0019)
  
  
• 91% of patients on EMPAVELI were transfusion free compared to 22% on standard of care (p<0.0001)
  
  
• The safety profile of EMPAVELI was consistent with previous studies
  

WALTHAM, Mass. and STOCKHOLM, Sweden, May 25, 2021 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) and Swedish Orphan Biovitrum AB (publ) (Sobi™) (STO:SOBI) today reported positive top-line results from the Phase 3 PRINCE study evaluating the efficacy and safety of EMPAVELI™ (pegcetacoplan) in adults with paroxysmal nocturnal hemoglobinuria (PNH) who are treatment naïve, meaning they had not received a complement inhibitor within three months before entering the study.

EMPAVELI demonstrated statistical superiority on the co-primary endpoints of hemoglobin stabilization and reduction in lactate dehydrogenase (LDH) compared to standard of care, which did not include complement inhibitors, at Week 26.

• 86% of EMPAVELI-treated patients achieved hemoglobin stabilization compared to 0% of patients on standard of care (p<0.0001). Hemoglobin stabilization was defined as an avoidance of a >1 g/dL decrease in hemoglobin levels in the absence of transfusions.
• Mean LDH in the EMPAVELI group decreased by 90% from a baseline of 2151 U/L [9.5x upper limit of normal (ULN)] to 211 U/L, which is within the normal range, compared to a 14% reduction on standard of care from a baseline of 1946 U/L (8.6x ULN) to 1681 U/L (7.4x ULN) (p<0.0001).

“The positive PRINCE data showed that EMPAVELI provided clinically meaningful improvements across multiple measures that are important for patients and build on our recent FDA approval of EMPAVELI in PNH,” said Federico Grossi, M.D., Ph.D., chief medical officer, Apellis. “Combined with previous studies, these results emphasize the potential of EMPAVELI to provide disease control for all adults with PNH regardless of prior treatment.”

EMPAVELI also achieved statistical superiority on several secondary endpoints, including improvements in hemoglobin levels and transfusion avoidance, compared to standard of care, which did not include complement inhibitors.

• Mean hemoglobin levels in the EMPAVELI group increased from 9.4 g/dL to 12.1 g/dL compared to an increase from a baseline of 8.7 g/dL to 9.4 g/dL on standard of care (p=0.0019).
• 91% of patients on EMPAVELI were transfusion free compared to 22% on standard of care (p<0.0001).

The safety profile of EMPAVELI was consistent with previous studies. At Week 26, 9% of patients in the EMPAVELI group experienced a serious adverse event (SAE) compared to 17% on standard of care. One death was reported in each group, and neither were related to treatment. No cases of meningitis or thrombosis were reported in either group. The most common adverse events reported during the study in the EMPAVELI and standard of care groups, respectively, were injection site reaction (30% vs. 0%),
hypokalemia (13% vs.11%), and fever (9% vs. 0%).

“The PRINCE study results reinforce the efficacy and safety profile of EMPAVELI in PNH,” said Ravi Rao, head of research and development and chief medical officer at Sobi. “Our hope is to contribute to an improvement of care and to make a difference in the lives of people with this rare blood disease.”

Detailed results from the PRINCE study will be presented at medical congresses.

About the PRINCE Study
The PRINCE study (NCT04085601) is a 2:1 (EMPAVELI: standard of care) randomized, multi-center, open-label, controlled Phase 3 study in 53 treatment-naïve adults with paroxysmal nocturnal hemoglobinuria (PNH). The primary objective of this study was to establish the efficacy and safety of EMPAVELI™ (pegcetacoplan) in patients who have not received treatment with any complement inhibitor within three months prior to screening. During the 26-week randomized, controlled period, patients received either 1080 mg of EMPAVELI twice weekly or standard of care therapy, which did not include complement inhibitors. Patients in the standard of care group had the option to escape to the EMPAVELI group if their hemoglobin decreased 2 g/dL or more from their baseline value.

The study was conducted in collaboration with SFJ Pharmaceuticals, who supported the development of EMPAVELI in PNH. SFJ is a global drug development company, which provides a unique and highly customized co-development partnering model for the world’s top pharmaceutical and biotechnology companies.

About EMPAVELI™ (pegcetacoplan)
EMPAVELI™ (pegcetacoplan) is the first and only approved therapy targeting C3, the central protein in the complement cascade. EMPAVELI acts proximally in the complement cascade controlling both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis. EMPAVELI is approved in the United States for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

U.S. Important Safety Information for EMPAVELI

BOXED WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA

• Meningococcal infections may occur in patients treated with EMPAVELI and may become rapidly life-threatening or fatal if not recognized and treated early. Use of EMPAVELI may predispose individuals to serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B.
• Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria.
• Vaccinate patients at least 2 weeks prior to administering the first dose of EMPAVELI unless the risks of delaying therapy with EMPAVELI outweigh the risk of developing a serious infection.
• Vaccination reduces, but does not eliminate, the risk of serious infections. Monitor patients for early signs of serious infections and evaluate immediately if infection is suspected.
• EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the EMPAVELI REMS, prescribers must enroll in the program.
  

CONTRAINDICATIONS

• Hypersensitivity to pegcetacoplan or to any of the excipients
• Not currently vaccinated against certain encapsulated bacteria, unless the risks of delaying EMPAVELI treatment outweigh the risks of developing a bacterial infection with an encapsulated organism
• Unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae
  

WARNINGS AND PRECAUTIONS

Serious Infections Caused by Encapsulated Bacteria
The use of EMPAVELI may predispose individuals to serious, life-threatening, or fatal infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B (Hib). To reduce the risk of infection, all patients must be vaccinated against these bacteria according to the most current ACIP recommendations for patients with altered immunocompetence associated with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI.

For patients without known history of vaccination, administer required vaccines at least 2 weeks prior to receiving the first dose of EMPAVELI. If immediate therapy with EMPAVELI is indicated, administer required vaccine as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis.

Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider discontinuation of EMPAVELI in patients who are undergoing treatment for serious infections.

EMPAVELI REMS
Because of the risk of serious infections, EMPAVELI is available only through a restricted program under a REMS. Under the EMPAVELI REMS, prescribers must enroll in the program and must counsel patients about the risk of serious infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria. Enrollment and additional information are available by telephone: 1-888-343-7073 or at www.empavelirems.com.

Infusion-Related Reactions
Systemic hypersensitivity reactions (e.g., facial swelling, rash, urticaria) have occurred in patients treated with EMPAVELI. One patient (less than 1% in clinical studies) experienced a serious allergic reaction which resolved after treatment with antihistamines. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue EMPAVELI infusion immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved.

Monitoring PNH Manifestations after Discontinuation of EMPAVELI
After discontinuing treatment with EMPAVELI, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH levels along with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues EMPAVELI for at least 8 weeks to detect hemolysis and other reactions. If hemolysis, including elevated LDH, occurs after discontinuation of EMPAVELI, consider restarting treatment with EMPAVELI.

Interference with Laboratory Tests
There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels.

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥10% of patients) with EMPAVELI vs. eculizumab were injection-site reactions (39% v. 5%), infections (29% v. 26%), diarrhea (22% v. 3%), abdominal pain (20% v. 10%), respiratory tract infection (15% v. 13%), viral infection (12% v. 8%), and fatigue (12% v. 23%).

USE IN SPECIFIC POPULATIONS

Females of Reproductive Potential
EMPAVELI may cause embryo-fetal harm when administered to pregnant women. Pregnancy testing is recommended for females of reproductive potential prior to treatment with EMPAVELI. Advise female patients of reproductive potential to use effective contraception during treatment with EMPAVELI and for 40 days after the last dose.

Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide.

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).

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 haematology, immunology and specialty indications. Today, Sobi employs approximately 1,500 people across Europe, North America, Middle East, and Asia. In 2020, Sobi's revenues amounted to SEK 15.3 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 in respect of the expected closing of the exchanges. 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 conditions for the closing of the exchanges will be satisfied and other factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q with the Securities and Exchange Commission on April 28, 2021 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
212.600.1902

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

Maria Kruse, Corporate Communication & Investor Relations
+ 46 767 248 830
maria.kruse@sobi.com

 

FAQ

What were the results of the Phase 3 PRINCE study for EMPAVELI (APLS)?

The Phase 3 PRINCE study demonstrated that EMPAVELI achieved statistical superiority in hemoglobin stabilization and reduction in lactate dehydrogenase compared to standard care.

How effective is EMPAVELI in treating paroxysmal nocturnal hemoglobinuria (PNH)?

EMPAVELI showed 86% hemoglobin stabilization and a significant 90% reduction in lactate dehydrogenase in clinical trials.

What percentage of patients on EMPAVELI remained transfusion-free?

91% of patients treated with EMPAVELI were transfusion-free at the end of the study.

What is the safety profile of EMPAVELI based on the PRINCE study?

The safety profile of EMPAVELI was consistent with prior studies, showing fewer serious adverse events compared to standard care.

What were the co-primary endpoints of the PRINCE study?

The co-primary endpoints were hemoglobin stabilization and reduction in lactate dehydrogenase levels, both of which were met with statistical significance.