How Soliris Works

[Joy Lewis O'Brien]

Hi All,
There is an accessible website called Rxlist.com that gives a lot of information about prescription and nonprescription drugs. In case any of you were curious how Soliris (eculizumab) works, here is the description from that site. Please note that the descriptions are for the approved use for treatment of PNH (paroxysmal nocturnal hematuria) as treatment for aHUS has not yet been fully approved and is still in trials. More information can be found here: http://www.rxlist.com/soliris-drug.htm

Mechanism of Action

Eculizumab, the active ingredient in Soliris, is a monoclonal antibody that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and
preventing the generation of the terminal complement complex C5b-9.
Soliris inhibits terminal complement mediated intravascular hemolysis
in PNH patients. [emphasis mine]

A genetic mutation in PNH patients leads to the generation of populations of abnormal RBCs
(known as PNH cells) that are deficient in terminal complement
inhibitors, rendering PNH RBCs sensitive to persistent terminal
complement-mediated destruction. The destruction and loss of these PNH
cells (intravascular hemolysis) results in low RBC
counts (anemia),
and also fatigue, difficulty in functioning, pain, dark urine,
shortness of breath, and blood clots.

Pharmacodynamics

In the placebo-controlled clinical study, Soliris when administered as recommended reduced hemolysis as shown by the reduction of serum
LDH
levels from 2200 ±
1034 U/L (mean ± SD) at baseline to 700 ± 388 U/L by week one
and maintained the effect through the end of the study at week 26 (327
±
433 U/L). In the single arm clinical study, Soliris maintained this
effect through
52 weeks [see CLINICAL STUDIES].

Pharmacokinetics

A population PK analysis with a standard 1-compartmental model was conducted on the multiple dose PK data from 40 PNH patients receiving the
recommended
Soliris regimen [see DOSAGE AND ADMINISTRATION].
In this model, the clearance of Soliris for a typical PNH patient
weighing 70
kg was 22 mL/hr and the volume of distribution was 7.7 L. The
half-life was
272 ± 82 hrs (mean ± SD). The mean observed peak and trough serum
concentrations of Soliris by week 26 were 194 ± 76 mcg/mL and 97 ±
60 mcg/mL, respectively.

Studies have not been conducted to evaluate the PK of Soliris in special patient populations identified by gender, race, age (pediatric or geriatric), or the presence of renal
or hepatic
impairment.

[Linda Burke]

Thanks, Joy - I appreciate you adding this very specific information on Soliris. As we discussed, it's been the best and most detailed info I've found anywhere. If someone else has additional information, we'd certainly welcome it!

[Joy Lewis O'Brien]

Whoops! I meant to put this in the Current Research forum, but I clearly clicked the wrong tab! Is there a way to move it? I could cut and paste and we could delete this as a new forum, if you like.

Linda Burke said:

Thanks, Joy - I appreciate you adding this very specific information on Soliris. As we discussed, it's been the best and most detailed info I've found anywhere. If someone else has additional information, we'd certainly welcome it!

[Cheryl Biermann]

Fantastic informatin thank youso much for posting here!