–  Results indicate up to 100% inhibition of alternative-pathway (AP) activity in hemolysis and Wieslab assays after oral dosing of ACH-4471  
–  Results support initiation of phase 1 multiple-ascending trial during the second quarter and phase 2 studies for paroxysmal nocturnal hemoglobinuria (PNH) and C3 glomerulopathy (C3G) by year-end 2016  –

NEW HAVEN, CT, USA I June 10, 2016 I Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today presented interim results from a phase 1 study with its novel small molecule factor D inhibitor, ACH-4471, at the 21st Congress of the European Hematology Association in Copenhagen, Denmark.

The e-poster entitled, “An Orally Administered Small Molecule Factor D Inhibitor (ACH-4471) For Treatment of PNH, C3G and Complement — Mediated Diseases: Interim Phase 1 Results In Healthy Volunteers” describes results from an ongoing phase 1 study led by Roderick B. Ellis-Pegler and Christian Schwabe of Auckland Clinical Studies Ltd, Auckland, New Zealand and a group of researchers from Achillion.

Across all four groups, ACH-4471 achieved peak plasma concentrations between 1 and 2.5 hours after oral dosing. Up to 100% inhibition of complement activity was achieved in all dose groups, and duration of inhibition was dose dependent. In addition, Group 4, which evaluated 1,200 mg of ACH-4471 given every twelve hours for 2 doses, achieved a median 99.5% inhibition (range 96 — 100%) of hemolysis at 24 hours.

“We are very encouraged by these data, which support our focus on developing potent, specific factor D inhibitor compounds, including ACH-4471, as a potentially novel approach to treating alternative pathway complement-mediated diseases such as PNH and C3G,” commented Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion. “Achieving sustained suppression of AP activity, as measured by the AP hemolysis and Wieslab assays, combined with modeling from these interim study results, suggest the potential for twice daily dosing to achieve sustained inhibition of AP activity.”

Study Design and Key Findings

The phase 1 study, initiated in February 2016, aims to assess the safety and tolerability of single ascending oral doses of ACH-4471 in healthy volunteers and to evaluate its pharmacokinetic (PK) and pharmacodynamic (PD) profile and PK/PD relationship as measured by the serum alternative pathway (AP) activity ex vivo.  

In the study, 36 subjects have been dosed and evaluated. Trial participants were assigned to one of four groups:

  • Group 1: 200 mg, single dose (6 active + 6 placebo subjects)
  • Group 2: 600 mg, single dose (6 active + 2 placebo subjects)
  • Group 3: 1200 mg, single dose (6 active + 2 placebo subjects)
  • Group 4: 1200 mg x 2 doses (Q12H) (6 active + 2 placebo subjects)

For all groups, inhibition of serum AP activity was evaluated using the AP Wieslab and hemolysis assays. Blood samples were collected from days 1 through 7 to determine plasma concentrations. Trial participants were monitored through the last scheduled visit at day 28 for any adverse events.

The interim study data indicate ACH-4471 was well-tolerated at all dose levels examined with no safety trends noted. Evaluation of serum AP activity by ex vivo assessment suggests rapid inhibition of AP activity after oral dosing. Furthermore, the concentrations of Bb, the cleavage product of factor B by factor D, were determined for the assessment of the inhibitory effect of ACH-4471 on in vivo factor D activity. Bb levels were shown to decline after dosing with ACH-4471 with the lowest Bb levels observed at 16 hours post-dosing in Groups 3 and 4 and a gradual return to baseline by 48 hours after dosing. 

Achillion plans to begin dosing in a phase 1 multiple-ascending dose study evaluating 14-days of dosing in healthy volunteers in June. The Company is also planning to initiate phase 2 studies of ACH-4471 in two complement-mediated diseases, PNH and C3G, by the end of 2016.

Abstracts for the 2016 Congress of the European Hematology Association are available online and can be accessed at http://www.ehaweb.org/. A reprint of the late breaking poster presentation will be available from the Resources section of the Achillion website at http://www.achillion.com.

About the Achillion Complement Factor D Platform

Achillion has leveraged its internal discovery capabilities and a novel complement-related platform to develop drug candidates that are oral inhibitors of complement factor D. Factor D is an essential serine protease involved in the complement pathway, a part of the innate immune system. Achillion’s complement platform is focused on seeking to advance small molecule compounds that inhibit factor D and can potentially be used in the treatment of immune-related diseases in which complement plays a critical role. Potential indications being evaluated for these compounds include paroxysmal nocturnal hemoglobinuria (PNH), C3 Glomerulopathy (C3G), dry age-related macular degeneration (dry AMD), and chronic obstructive pulmonary disease (COPD). Achillion anticipates that its platform could play a role in addressing the needs of all PNH patients, including patients who have suboptimal response to, or fail to respond to, the currently available treatments, as well as for patients suffering from other alternative pathway complement-mediated diseases. Achillion nominated ACH-4471 for clinical development in December 2015, and initiated clinical development in February 2016.

About Achillion Pharmaceuticals

Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) is a science-driven, patient-focused company seeking to leverage its strengths across the continuum from discovery to commercialization in its goal of providing better treatments for people with serious diseases. The company employs a highly-disciplined discovery and development approach that has allowed it to pursue best-in-class oral antiviral therapy for chronic hepatitis C (HCV) and build a platform of potent and specific complement inhibitors. Achillion is rapidly advancing its efforts to become a fully-integrated pharmaceutical company with a goal of bringing life-saving medicines to patients with rare diseases. More information is available at http://www.achillion.com.

SOURCE: Achillion Pharmaceuticals