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Islets xenotransplantation: New Zealand experience

Olga Garkavenko, Robert Elliott

Living Cell Technologies, Auckland, New Zealand

To meet regulatory requirements for xenotransplantation an elaborate program on xenovirology has been under development and implementation at LCT since 1997. This program allowed LCT to allocate one specific herd of pigs that was free from all conventional pathogens and was also qualified as “null” pigs or pigs that do not have a transmittable pig endogenous retrovirus (PERV). These pigs are the animal-founders for a DPF donor herd. A comprehensive program for patients’ microbiology follow-up was also developed. This program includes assays developing for monitoring potential infection with PERV and other potentially xenotic pathogens.

Compliance with the requirements from New Zealand government allowed LCT to successfully complete its application for a clinical trial using porcine islets. In 2009 the New Zealand Government approved an open-label phase I/IIa safety/efficacy clinical trial using porcine islet cells. The primary objectives for the phase I/IIa clinical trial are the safety of xenotransplantation of DIABECELL® and improvement in blood glucose level reflected in a decrease of HbA1c (%) level. The secondary objectives include glucose lability, reduction of insulin dose and decrease in hypoglycaemia frequency and severity. A total of fourteen patients with severe unaware hypoglycaemia were enrolled into the trial and allocated to one of the four dosage groups, which range from 5,000 – 20,000 IEQ/kg delivered in a single dose. In October 2009 the first New Zealand patient was transplanted with DIABECELL®.

To date LCT reports that the trial is meeting objectives for safety. All fourteen patients were screened for the presence of pig viruses including PERV. There was no evidence of PERV infection during the 52 weeks of monitoring. Minimal reduction in insulin dose and HbA1c has been reported in transplant patients. However there has been a marked improvement in hypoglycaemic episodes, with patients showing a decrease in the severity of these episodes as well as a reduction in unaware hypoglycaemia.