Achillion Reports Positive Interim Data for ACH-4471 Phase 2 Combination Trial with Eculizumab at The New Era of Aplastic Anemia and PNH Meeting

- ACH-4471 increased hemoglobin and nearly eliminated the need for transfusions in patients with PNH being treated with C5 inhibitor, eculizumab -

BLUE BELL, PA, USA I May 17, 2019 I Achillion Pharmaceuticals, Inc. (Nasdaq: ACHN), a clinical-stage biopharmaceutical company dedicated to transforming the lives of patients and families affected by complement-mediated diseases, today reported interim data from a Phase 2 paroxysmal nocturnal hemoglobinuria (PNH) trial assessing the safety and effectiveness of its oral small molecule factor D inhibitor ACH-4471 in combination with intravenous eculizumab at The New Era of Aplastic Anemia and PNH Meeting in Naples, Italy.

“Anemia is a persistent problem in the majority of patients with PNH treated with standard and even high doses of eculizumab. These interim data are encouraging and demonstrate that ACH-4471, when used in combination with a C5 inhibitor, such as eculizumab, has the potential to improve anemia, decrease transfusions and lead to improvement in important clinical parameters of hemolysis as well as quality of life measurements for patients with this devastating condition,” stated Joseph Truitt, Chief Executive Officer at Achillion.

ACH-4471 Interim Data
This proof-of-concept, 24-week trial is ongoing. Interim data in 11 enrolled patients were assessed between 4 to 24 weeks, depending on the patient’s current treatment duration in the dose escalating trial. The oral presentation features the following data:

  • Increases in mean hemoglobin of approximately 2 g/dL at week 4 (n=11); for the 4 patients that have reached 24 weeks their mean rise in hemoglobin is 2.6 g/dL;  
  • A reduction in blood transfusions from 34 transfusions totaling 58 units in the 24 weeks prior to screening to only 1 transfusion of 2 units during treatment with ACH-4471;
  • Meaningful improvement in Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scores versus baseline, with a mean score increase of 11 at week 4;
  • Increase in the percentage of PNH RBC Type III clone size from 40% at baseline to 71% at week 12 (n=8);
  • Reduction in total bilirubin from a mean of 2.17 mg/dL to 1.21 mg/dL at week 16 (n=8);
  • Reduction in mean reticulocytes from 219 10^9/uL at baseline to 153 10^9/uL at week 16 (n=8);
  • Further reduction of LDH into the normal range;
  • Four patients are currently receiving the lowest study dose of 100 mg three times a day;
  • ACH-4471 was generally well tolerated when added to eculizumab in patients with PNH.

“In patients treated with C5 inhibitors alone, extravascular hemolysis (EVH) is an ongoing problem resulting in anemia with an impact on most of the clinical parameters of hemolysis. These interim findings from this important proof-of-concept trial show that if the alternative pathway is adequately inhibited, important parameters of EVH can be improved, including and most importantly hemoglobin, transfusion, bilirubin, reticulocyte count, and FACIT fatigue scores, when added to stable optimal dose eculizumab therapy. We look forward to completing the Phase 2 trial this summer and future discussions with the regulatory authorities. After completion of regulatory discussions, we hope to initiate a Phase 3 PNH combination trial of ACH-4471 with C5 inhibitors in the first half of 2020,” stated Steven Zelenkofske, D.O. Chief Medical Officer at Achillion.

Slides from the oral presentation will be available on the Company’s website, today, May 17, at approximately 9:00 a.m. EST at

ACH-4471 Phase 2 Trial in Combination with Eculizumab
ACH-4471 is being evaluated in combination with eculizumab, an intravenous C5 inhibitor that is currently approved as monotherapy for PNH. This is a Phase 2, open-label, multiple dose trial in adult patients on stable eculizumab treatment with blood transfusion dependent anemia, defined as receiving at least one transfusion in the 12 weeks prior to the study and a hemoglobin level below 10 g/dL. In addition to their usual dose of eculizumab, patients are administered ACH-4471 orally three times a day at a dose determined by patient clinical response. The primary outcome of the trial is the change in hemoglobin at 24 weeks compared to baseline.  Secondary outcomes include the number of blood transfusions required, impact on selected clinical parameters, and safety. The trial will be followed by a long-term extension phase.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is thought to be caused by a mutation resulting in the absence of receptors normally present on red blood cells (RBCs) that interact with the complement system. The complement system typically functions normally in these patients but due to the lack of key receptors, known as CD55 and CD59, on the surface of PNH RBCs, the complement system treats these cells as foreign and destroys them via hemolysis in the circulatory system (intravascular) and in the liver or spleen (extravascular). The complement alternative pathway (AP) is a critical factor in the development of extravascular hemolysis. Complement factor D is a critical protein within the amplification loop of the AP and it is believed that inhibiting it could control the AP response. Furthermore, this mechanism of action represents a potentially distinct and unique therapeutic approach for controlling intravascular and extravascular hemolysis associated with PNH.

More information is available at

About Achillion Pharmaceuticals
Achillion Pharmaceuticals, Inc. (Nasdaq: ACHN) is a clinical-stage biopharmaceutical company focused on advancing its oral small molecule complement inhibitors into late-stage development and commercialization. Research has shown that an overactive complement system plays a critical role in multiple disease conditions including the therapeutic areas of nephrology, hematology, ophthalmology and neurology. Achillion is initially focusing its drug development activities on complement-mediated diseases where there are no approved therapies or where existing therapies are inadequate for patients. Potential indications being evaluated for its compounds include paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulopathy (C3G), and immune complex membranoproliferative glomerulonephritis (IC-MPGN). Each of the product candidates in the Company’s oral small molecule portfolio was discovered in its laboratories and is wholly owned. To advance its investigational product candidates into Phase 3 clinical trials and commercialization, the Company plans to work closely with key stakeholders including healthcare professionals, patients, regulators and payors.

More information is available at

SOURCE: Achillion Pharmaceuticals

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