Apellis Pharmaceuticals Provides Update on Phase 1b Open Label Study of APL-2 in PNH Patients Not Previously Treated with Eculizumab

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CRESTWOOD, Ky. and WALTHAM, Mass., April 16, 2018 (GLOBE NEWSWIRE) --  (Nasdaq:APLS), a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds for the treatment of autoimmune and inflammatory diseases, today announced interim data from its Phase 1b PADDOCK trial for patients with paroxysmal nocturnal hemoglobinuria (PNH).  The ongoing trial is evaluating the treatment with APL-2, a novel inhibitor of complement factor C3, in patients not previously treated with eculizumab (Soliris). 

The Company previously that APL-2 reduced lactate dehydrogenase (LDH) and increased hemoglobin (Hgb) levels in three patients not previously treated with eculizumab after daily subcutaneous administration of 270 mg of APL-2 for 28 days in the trial.  Based on the safety and activity observed in these patients, the administration period was extended from 28 days to one year and the number of patients to be enrolled in the PADDOCK trial was increased.  As of April 13, 2018, the data cut-off date for this interim analysis, six more patients have been treated with APL-2 at the 270 mg/day dose for a minimum of 28 days.  The data being announced today excludes results from one of the original three patients, who had underlying metastatic ovarian cancer with a chronic low gastrointestinal bleed, unknown at the time of screening, which resulted in artificially low Hgb and high LDH levels that were determined to be unrelated to PNH, and also excludes results from the initial cohort of two patients treated with APL-2 at a dose of 180 mg/day.

The eight eculizumab naïve patients reported here and treated with a 270 mg/day dose of APL-2 had a mean LDH of 11.6x the upper limit of normal (ULN), which is 250 U/L, at baseline that was reduced to 0.9x ULN by day 28.  Seven of the eight patients (88%) had LDH levels below the upper limit of normal at day 28.  The table below and included figure show the decrease in the mean LDH levels, as a multiple of the upper limit of normal, over their respective treatment periods (up to the first eight weeks) in the eight reported patients in the PADDOCK trial who received a daily dose of 270 mg of APL-2 and were treated for at least 28 days.

The same eight patients had an average increase in hemoglobin of 4.3 g/dL, from a baseline average of 7.9 g/dL to an average last measurement of 12.2 g/dL (range 11.9-12.9 g/dL) within the first 12 weeks of the treatment period (12 g/dL = lower limit of normal for Hgb).  Except for two patients each of whom received a single transfusion within the first two weeks of treatment, no other transfusions have been reported in this study for any patients during the treatment period with APL-2.  The table below and included figure show the measurement of hemoglobin levels for each of these eight patients to date over their respective treatment periods (up to 12 weeks).

"While the LDH corrections seen with APL-2 monotherapy in these patients with PNH are exciting, it is the significant hemoglobin correction that is most clinically meaningful,” said Peter Hillmen, Professor of Experimental Hematology at the Leeds Institute of Cancer & Pathology.  “LDH is a good measure of intravascular hemolysis but neither LDH nor transfusion avoidance captures the ongoing anemia resulting from extravascular hemolysis seen in patients with PNH on treatment with eculizumab and other C5 inhibitors.”

Substantial improvements in other biomarkers of anemia were observed.  The same eight patients had an average reduction in absolute reticulocyte count of 50% from 195 10^9/L to 97 10^9/L (normal = 30-100 10^9/L) over 28 days.  Bilirubin in these patients was reduced from an average baseline of 42 umol/L to an average of 11 umol/L at day 28 (normal = 3-15 umol/L), an average decrease of 74%. The table below and included figure show the decreases in average reticulocyte count and average bilirubin level in the first 8 weeks of treatment.

“The overall hematological improvement with APL-2 in these patients with PNH is very encouraging and suggests a promising approach for management of PNH patients in the future,” noted Anita Hill, Lead Consultant for the National PNH Service at the Leeds Teaching Hospitals, U.K.  “Elevated reticulocytes and elevated bilirubin are important markers of anemia resulting from extravascular hemolysis and are not known to improve in patients treated with eculizumab or other C5 inhibitors.”

To date, APL-2 has generally been well-tolerated in these patients.  APL-2 has been administered systemically in the Company’s PNH clinical trials with more than 3,800 subcutaneous doses of 270 mg/day or more, representing cumulative systemic exposure of over 525 patient weeks of treatment on APL-2.  No significant infections or thromboembolic events have been observed.                                                                                                                     “We are extremely pleased with these early results from the PADDOCK study,” said Dr. Cedric Francois, MD, PhD, Founder and Chief Executive Officer of Apellis.  “We believe that the results demonstrating broad hematological correction in these patients suggest that APL-2 monotherapy has the potential to be a superior treatment option for patients with PNH.  These interim results are a step forward in our mission to improve the lives of patients suffering from unmet needs in complement mediated conditions.  We look forward to reporting further updates to the ongoing PADDOCK trial in June.”

In the second half of 2018, the Company plans to initiate a Phase 3 clinical trial in approximately 70 patients with PNH comparing treatment with APL-2 monotherapy to treatment with eculizumab. Discussions are ongoing with the FDA, the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) regarding details of the clinical data that will be required to support regulatory approval of APL-2 monotherapy as a first-line treatment for PNH.

The photos accompanying this announcement are available at:

Tully Nicholas  617.482.0042  (office) 860.490.0218  (mobile)

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Globe Newswire: 14:23 GMT Monday 16th April 2018

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