Apellis Pharmaceuticals Provides Update on Two Phase Ib Trials for Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

  • Severely anemic patients with PNH on treatment with Soliris™ can become transfusion-free with improved hemoglobin when switched to APL-2 monotherapy.
  • Treatment-naïve patients with PNH show clinically meaningful improvements for all hematological parameters when treated with APL-2.


CRESTWOOD, Ky. and WALTHAM, Mass. —  Apellis Pharmaceuticals, Inc.  (Nasdaq:APLS), a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds to treat disease through the inhibition of the complement system, will provide clinical updates today on its two ongoing Phase Ib PNH studies during an R&D Day in New York between 2.00 pm and 5.00 pm.

Apellis is developing APL-2 for the treatment of PNH, a rare, acquired, potentially life-threatening disease characterized by complement-mediated thrombosis and hemolytic anemia.  The Company believes that by targeting C3, APL-2 can improve hematological parameters in patients with PNH on treatment with C5 inhibitors such as eculizumab (Soliris™).  Specifically, the Company believes that APL-2 has the potential to significantly improve hemoglobin (Hb) levels in eculizumab-treated patients suffering from anemia.  In a recent study, up to 70% of patients treated with eculizumab, the only currently approved therapy for PNH, were anemic, with hemoglobin levels below 12.0 g/dL.1  Apellis’ clinical PNH program is designed to allow patients with PNH to switch from eculizumab to APL-2 monotherapy after one month of co-treatment with the goal of improving hematological parameters, particularly hemoglobin.

Apellis has two ongoing Phase Ib proof-of-concept clinical trials evaluating APL-2 in PNH: PHAROAH and PADDOCK.  The PHAROAH trial is evaluating whether APL-2 can provide benefits to patients on treatment with eculizumab who are severely anemic and transfusion-dependent.  Patients have been treated with APL-2 in addition to eculizumab and several patients have been switched to APL-2 monotherapy after at least a year of co-treatment.  The PADDOCK trial is evaluating the safety and efficacy of APL-2 in patients with PNH not previously treated with eculizumab.

PHAROAH Trial Update

The 32 week data for the trial were released last December at the International PNH Interest Group meeting, with six patients enrolled to receive co-treatment of eculizumab and APL-2 at 270 mg/day. The four patients who remained in the study (as of week 32) have remained in the study for an average of 92 weeks.  Key findings include:

  • No transfusions needed: The average Hb for the four patients before starting combined dosing with APL-2 was 8.9 g/dL.  These patients received an average of 6.0 transfusions on eculizumab in the 52 weeks before co-treatment with APL-2.  Since commencing co-treatment with APL-2, including and since the weaning from eculizumab, there have been no transfusions in any of the four patients.
  • Successful reduction in dosing of eculizumab: At baseline, three of the four patients were on higher than label dose (900 mg every 2 weeks) of eculizumab.  During the evaluation period, the treating physicians reduced dosing with eculizumab to label dose in all four patients without hematological impact.
  • Successful weaning from eculizumab: Three of the four patients have thus far been weaned from eculizumab and treated with APL-2 monotherapy for 7, 23 and 30 weeks.  Following weaning, all three patients remained hematologically stable with no transfusions and stable average hemoglobin of 11.8 g/dL at most recent measure (normal Hb >12.0 g/dL).  This represents an average hemoglobin increase of 2.3 g/dL from the baseline established with eculizumab monotherapy.  All three patients have also maintained lactate dehydrogenase (LDH) in the normal range, with an average last measure of 0.76x upper limit of normal (ULN).  The fourth patient, with a BMI of 46, was hematologically stable when the dose of eculizumab was reduced from twice label to normal label dose but showed elevated LDH levels when eculizumab was discontinued completely, leading to a restart with eculizumab.  Since biomarkers suggested under-dosing, the dose of APL-2 will be increased before attempting to wean from eculizumab treatment again.  At last measure, on APL-2 and label eculizumab dose, this patient had a hemoglobin of 11.3 g/dL vs. a baseline of 7.0 g/dL when the patient received twice the label dose of eculizumab and required 9 transfusions in the prior 52 weeks.  This change in Hb represents an increase of 4.3 g/dL compared to baseline as well as zero transfusions in the 87 weeks on co-treatment with APL-2.


“It was initially very encouraging to see the significant improvement in these significantly anemic patients when APL-2 was added to Soliris™,” said Anita Hill, Lead Consultant for the National PNH Service at the Leeds Teaching Hospitals, U.K.   “To see APL-2 maintain the same hematological benefits when dosing with Soliris™ was reduced in all and weaned entirely in three of four patients is impressive.”

PADDOCK Trial Update

In April 2018, the Company reported that APL-2 increased Hb levels and reduced LDH in eight patients not previously treated with eculizumab after daily subcutaneous administration with 270 mg/day of APL-2 for at least 28 days.  Five additional patients have been enrolled and are evaluable for at least 28 days.  At baseline, the average hemoglobin level for the 13 patients was 8.4 g/dL and average LDH level was 9.5x ULN.  As of June 19th, 2018, eight patients have been on APL-2 for over 8 weeks and 4 have reached 16 weeks of treatment.  Key findings include:

  • Improved hemoglobin and other anemia markers: In the last reading, the average Hb from each patient on APL-2 was 11.9 g/dL, an increase of 3.5 g/dL over baseline.  Average bilirubin and reticulocytes, which are markers for anemia, were in the normal range.  Two total transfusions were given in the study, one at day two in one patient and one at day 14 in a non-compliant patient; it is believed that neither patient had yet reached sufficient exposure to APL-2 for hematological benefit.
  • Improved LDH: The average LDH level at week 4 was 0.8x ULN and has remained within the normal range beyond week 4.


“The data generated by APL-2 in treatment-naïve patients with PNH are impressive compared to our experience with Soliris™,” said Dr. Peter Hillmen, Professor of Experimental Hematology, University of Leeds, Leeds, UK.  “The early experience of APL-2 demonstrates that inhibiting C3 controls extravascular as well as intravascular hemolysis unlike inhibition of C5 where continued extravascular hemolysis is frequently problematic.”

“We are especially pleased to see APL-2 monotherapy helping a range of patients, including those who are severely anemic and continue to suffer while being treated with high doses of eculizumab,” said Dr. Cedric Francois, M.D., Ph.D., co-founder and CEO of Apellis. “We are encouraged by these data that support our belief that many rare and autoimmune conditions can be treated through C3 inhibition, and we look forward to having Dr. Hillmen and Dr. Hill present the detailed results at our R&D Day today.”

To date, subcutaneous APL-2 has generally been well-tolerated with cumulative systemic exposure of over 12 patient years of treatment on APL-2.  No significant infections or thromboembolic events have been observed.

The live webcast and slide presentation for the R&D Day may be accessed by visiting the “Events and Presentations” page of the “Investors and Media” section of the Company’s website at http://www.apellis.com.  Replay of the webcast will be available for 90 days following the event.

About Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, potentially life-threatening disease characterized by complement-mediated hemolysis with or without hemoglobinuria, an increased susceptibility to thrombotic episodes and/or some degree of bone marrow dysfunction. A significant subset of patients treated with the current standard of care still suffer from debilitating anemia and transfusion dependence.

About the PHAROAH Trial

PHAROAH is an ongoing open label safety and efficacy study of 270 mg of APL-2 administered daily by subcutaneous injection as a complementary therapy to patients with PNH who continue to be anemic (Hb <10 g/dL at screening or have a history of at least one transfusion in the previous year) despite treatment with eculizumab. The PHAROAH study was initiated in November 2014 and is being conducted at multiple clinical sites in the United States.

About the PADDOCK trial

PADDOCK is an ongoing open-label Phase Ib safety and efficacy study of 270 mg of APL-2 administered daily by subcutaneous injection to patients with PNH who have never received eculizumab.  The PADDOCK study was initiated in December 2015 and is being conducted at multiple clinical sites outside of the United States.

About APL-2

APL-2 is designed to inhibit the complement cascade centrally at C3 and may have the potential to treat a wide range of complement-mediated diseases more effectively than is possible with partial inhibitors of complement. APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that binds specifically to C3 and C3b, effectively blocking all three pathways of complement activation (classical, lectin, and alternative). Apellis is currently evaluating APL-2 in two Phase Ib clinical trials for systemic administration in paroxysmal nocturnal hemoglobinuria (the PHAROAH trial and the PADDOCK trial).  Apellis is also testing APL-2 for systemic administration in a Phase II clinical trial in autoimmune hemolytic anemia (AIHA) and a Phase II clinical trial in complement dependent nephropathies, as well as a Phase Ib/II clinical trial evaluating intravitreal APL-2 in wet age-related macular degeneration.  Phase III studies are planned in intravitreal APL-2 for geographic atrophy (GA) and PNH.  Future clinical studies of APL-2 are anticipated in other diseases in which complement is implicated.

About Apellis

Apellis Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds for the treatment of a broad range of life-threatening or debilitating autoimmune diseases based upon complement immunotherapy through the inhibition of the complement system at the level of C3. Apellis is the first company to advance chronic therapy with a C3 inhibitor into clinical trials. For additional information about Apellis and APL-2, please visit http://www.apellis.com/.

Forward-Looking Statements

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 preliminary or interim results from a clinical trial such as the results reported in this release 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 APL-2 will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of such clinical trials will warrant regulatory submissions and whether APL-2 will receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies for GA, PNH or any other indication; 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 April 30, 2018 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.


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