Achillion Pharmaceuticals


Advancing Factor D Inhibition into Late-Stage Clinical Development

At Achillion, we are focused on advancing our clinical-stage portfolio of small molecule, orally administered factor D inhibitors into late-stage development and potential commercialization for patients with devastating rare disorders mediated by the complement Alternative Pathway (AP). Our first-generation, oral factor D inhibitor, ACH-4471, has demonstrated initial proof-of-mechanism in both C3 glomerulopathy (C3G) and paroxysmal nocturnal hemoglobinuria (PNH), with development expanded into global, Phase 2 clinical programs. In addition to ACH-4471, we have advanced the next-generation, oral factor D inhibitors, ACH-5228 and ACH-5448, from our proprietary complement platform into clinic with Phase 1 studies.


ACH-4471 is an investigational, oral, factor D inhibitor that has demonstrated initial proof-of-concept in two rare disorders mediated by the complement alternative pathway – C3 glomerulopathy (C3G) and paroxysmal nocturnal hemoglobinuria (PNH). ACH-4471 has been granted orphan drug designation for the treatment of each condition in both the United States and European Union.

ACH-4471 is being evaluated in an ongoing global, Phase 2 clinical program as a potential treatment for patients with C3G, including patients with dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The ongoing clinical program includes a 14-day biomarker study, a six-month blinded, placebo-controlled study, and a 12-month open label study. In May 2018, Achillion presented preliminary data from the 14-day biomarker study at the 55th ERA-EDTA Congress in Copenhagen, Denmark demonstrating reductions in multiple markers of AP activity and a ~50% reduction in urine protein in C3G patients (n=4).

ACH-4471 is also being assessed as potential treatment for patients with PNH in an ongoing global, Phase 2 clinical program. The orally, administered factor D inhibitor is being studied in both naïve patients as monotherapy, and in patients treated with, but sub-optimally responding to, eculizumab.

For more information on the ongoing, global Phase 2 clinical programs for ACH-4471, please visit Patient and Clinicians

Next-generation Factor D Inhibitors:

Both ACH-5228 and ACH-5548 are next-generation factor D inhibitors being developed for oral administration. These compounds have demonstrated enhanced potency as well as optimized pharmacokinetic properties that may allow for reduced frequency of dosing. Both compounds are in Phase 1 clinical assessment.

Complement Factor D Platform:

Achillion has leveraged its internal discovery capabilities and a novel complement-related platform to develop small molecule drug candidates that are inhibitors of complement factor D. Achillion has generated over 3,000 small-molecule compounds and a substantial subset of them are potent and specific inhibitors of complement factor D, with physicochemical properties suitable for various routes of administration. Achillion identified and advanced the oral, factor D inhibitors, ACH-4471, ACH-5228, and ACH-5548 into clinical development from this proprietary platform.

ACH-4471, ACH-5228, and ACH-5548 are investigational compounds. Their safety and efficacy have not been established.