Alexion Pharmaceuticals - PNH Clinical Programs

PNH Clinical Programs

The safety and efficacy (benefit) of Soliris was studied in three clinical trials in 195 patients with PNH.^14-16 The pivotal clinical trial, named the TRIUMPH study, demonstrated the efficacy and safety of Soliris^® (eculizumab) for the treatment of patients with PNH.¹⁴ Safety and efficacy data obtained from additional studies^15,16 also served as the basis for regulatory approval of the product.

Ongoing research is providing valuable insight into PNH and its treatment.^17,18 A number of publications, presentations and reports describe the medical complications associated with PNH, including severe and disabling fatigue, abdominal pain, difficulty swallowing, erectile dysfunction, kidney and liver failure, pulmonary hypertension, anemia (often requiring transfusions), pain and increased risk of blood clots (thrombosis). These studies have also supported the role of complement associated with PNH and the benefits of Soliris therapy. Some examples include:

Quality of Life: Clinical studies published in the New England Journal of Medicine and Blood, the journal of the American Society of Hematology, demonstrated that patients with PNH suffer a poor quality of life.^14-16 Utilizing a clinical test to measure changes in fatigue (FACIT-fatigue scale) and quality of life (EORTC-QLQ-C30), these studies showed that patients are often forced to modify their daily activities due to the severity of their symptoms. Patients treated with Soliris showed significant improvement such as reduced severity of fatigue and increased quality of life.
Thrombosis: Blood clots (thrombosis) are the leading cause of death in patients with PNH, and approximately 40 percent of patients with PNH are diagnosed with blood clots during the course of the disease.¹ An analysis of clinical studies published in the journal Blood indicated that PNH patients treated with Soliris experienced 92 percent fewer life-threatening blood clots compared to the same period of time prior to treatment.¹⁷ This analysis also demonstrated that, prior to initiation of treatment with Soliris, the incidence of blood clots was still markedly elevated in patients with PNH who were treated with antithrombotic therapy. The majority of patients (56%) in the clinical trials received antithrombotic therapy during the trials and these patients showed a benefit with Soliris.¹⁷ The effect of anticoagulant withdrawal during Soliris treatment has not been studied.¹⁹
Measures of Clotting: In a separate study performed by an independent investigator, treatment with Soliris resulted in a rapid, sustained decrease in blood measures associated with the risk of developing blood clots and inflammation in patients with PNH.²⁰ These data were presented at the American Society of Hematology (ASH) annual meeting in December 2008. This study may help researchers better understand disease mechanisms common to other complement-inhibitor deficiency disorders.
Kidney Function: Patients with PNH are six times more likely than the general public to have chronic kidney disease as defined by the National Kidney Foundation.^21,22 An analysis of clinical data found that patients with PNH treated with Soliris saw significant improvement and/or stabilization of kidney function (P=0.04) by six months when compared to patients in the placebo group. These data were presented at the American Society of Hematology (ASH) annual meeting in December 2007.²²
Pulmonary Hypertension: Recently it has been demonstrated that patients with PNH suffer from pulmonary hypertension,⁵ an increase in blood pressure in the blood vessels of the lung. This results in shortness of breath and extreme fatigue. An analysis of the Phase III TRIUMPH study showed that 47 percent of patients with PNH were suffering from pulmonary hypertension before starting the trial, as measured by the levels of NT-BNP, a measure of pulmonary hypertension.⁴ Soliris reduced the number of patients with pulmonary hypertension by 50 percent compared to placebo.⁴ These data were presented at the American Society of Hematology (ASH) annual meeting in December 2008.

Alexion continues to examine the therapeutic value of Soliris for the treatment of PNH in other populations. Recently Alexion completed a clinical trial in Japan. This open-label registration study, called AEGIS, examined the safety and efficacy of Soliris treatment in Japanese patients with PNH. The results were reported in December 2008.²³ The primary efficacy endpoint of reducing elevated red blood cell destruction was achieved with statistical significance, and the drug appeared to be safe and well-tolerated in the study patients. This study demonstrated similar safety and efficacy results in Asian / Japanese populations as had been seen previously in U.S. and European patient populations. In early 2009, the company submitted an application for marketing authorization of Soliris to Japan's Pharmaceutical and Medical Device Administration (PMDA).