NEW ORLEANS, La.—Researchers highlight the many trials that contributed to the development of therapies and treatment for paroxysmal nocturnal hemoglobinuria, according to a recent session held at the 64th ASH Annual Meeting and Exposition.

PNH is the archetypal complement disorder. Patients with PNH often experience intravascular hemolysis, thrombosis, bone marrow failure, and anemia. Intravascular hemolysis involves severe lethargy, dysphagia, erectile failure, abdominal pain, and disabling symptoms, noted Peter Hillmen, MD, PhD, of University of Leeds School of Medicine. PNH is an acquired clonal disorder or complement, he added.

Prior research published in the New England Journal of Medicine in 1995 showed that patients with PNH had a median survival of 10 years, while 28% lived for 25 years or longer, said Hillmen.

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The researchers found that 39% had venous thrombosis and 8 patients had arterial thrombosis.

Other data showed that 15% of patients had spontaneous remission, which included 12 of 35 patients surviving in about 10 year’s time, Hillmen said.

Prior research also showed that many patients had PNH type 3 cells, noted Hillmen. The prior literature showed that many patients had 2 types of PNH cells, he continued.

This is largely due to the deficiency of 2 complement regulators, he added.

Type 3 cells are complement deficient in CD3 59 and type 2 cells are partially deficient, explaining the varying sensitivity, Hillmen said.

Researchers also focused on the biology of the disease. They showed that patients were unable to make GPI molecules, he said.

Collaboration with Alexion and anti-C5 Moab led to the initial development of cardiac indications and autoimmune diseases. h5G1.1-mAb is now known as eculizumab, noted Hillmen.

Researchers eventually assessed h5G1.1-mAb for the treatment of PNH, he added.

The PNH Pilot study included a 69-year-old male patient. He was diagnosed with aplastic anemia in 1988 and later diagnosed with PNH in 1993. He had erectile dysfunction, abdominal pain, severe lethargy. He began taking eculizumab in May 2002.

Another patient was a 79-year-old male farmer who was diagnosed with aplastic anemia in 1984. He had severe lethargy, abdominal pain, hemoglobinuria, and erectile dysfunction. The patient was prescribed with eculizumab in May 2002.

The Pilot Study in 2002, the TRIUMP study in 2004, and the SHEPHERD study in 2005 led to the regulatory approval of eculizumab for PNH in 2006, noted Hillmen.

All in all, there were a number of pivotal trials and research advancing moments that contributed to the approval of eculizumab for the treatment of PNH, Hillmen concluded.  


Atkinson J, Hillmen P. Ernest Beutler lecture and prize: the complement system and medicine: the good, the bad, the future.  64th ASH Annual Meeting and Exposition. New Orleans, LA; December 10-13, 2022.