Phase I trial of CPHPC + anti-SAP antibodies

An abstract summarising the findings of the initial part of the Phase I trial of the obligate therapeutic partnership of CPHPC plus anti-SAP antibodies in patients with systemic amyloidosis was presented at the Annual Meeting of the Association of Physicians 27 March 2015.

This was the first in human clinical trial of a first in class treatment that has never been used before. The main aim was to show that the drug combination is safe and acceptably tolerated in patients.

Patients with amyloid in the heart were excluded from this first part of the trial for safety reasons. We have substantial experience with CPHPC in amyloid patients and it has always been absolutely safe but anti-SAP antibodies have not previously been given. The initial antibody doses were accordingly very small but in the absence of any ill effects, larger doses were given and were generally well tolerated.

Most of the patients were selected because they had amyloid affecting the liver as well as some other organs. There are several different powerful methods for assessing both liver amyloid load and liver function.

The important results of the trial so far are as follows:

1. The treatment is safe and well tolerated.

2. After treatment with a sufficient antibody dose, there was evidence of reduction in amyloid load in almost all subjects. This was associated with improved liver function in some subjects.

This finding is unprecedented.

There has never been any other treatment that directly targets amyloid deposits nor any intervention which produces such rapid clearance of amyloid from the tissues.

In some individuals the disappearance of amyloid was dramatic and in others, with much larger initial amyloid load, it was more subtle. Crucially the dose level at which amyloid clearance was seen was much smaller than the optimal dose used in the mouse experiments on which this new clinical treatment was based. Further experience with larger and repeated antibody doses, not yet reported, shows that additional clearance from the liver and other organs can be achieved.

The present trial is continuing and plans for a Phase II trial, aiming to confirm clinical efficacy and patient benefit are in progress. However the results so far have shown convincingly that reduction in amyloid load in the tissues leads to improved organ function.