New approach to lupus in clinical trials

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New approach to lupus in clinical trials

Rheumawire

Aug 19, 2004

Nainggolan

Dusseldorf, Germany - A novel approach to the treatment of systemic

lupus erythematosus (SLE) is in early clinical trials, following 2 pilot

studies that demonstrated safety and proof of principle of the new

antigen-based heteropolymer agent [1].

Reporting in the September 2004 issue of the ls of the Rheumatic

Diseases, Dr C Iking-Konert (Rheumazentrum, Dusseldorf, Germany) and

colleagues describe the pilot studies with the new compound in both

healthy volunteers and SLE patients.

" The data provide the basis for further development of this technology

as a treatment option for numerous indicationsfor example, autoimmune

diseases such as SLE, " they state.

The approach is based on the principle of immune adherence: it consists

of a heteropolymer of 2 cross-linked monoclonal antibodies, 1 of which

is directed to the complement receptor, CR1, found on erythrocytes, and

the other to a target pathogen/antigen. The new technology is being

developed by Elusys Therapeutics Inc (Pine Brook, NJ).

Iking-Konert et al conducted their studies with ETI-104, a murine

monoclonal antibody to CR1 cross-linked to double-stranded DNA (dsDNA).

" In humans, the presence of dsDNA is virtually diagnostic for SLE and

rarely occurs in other conditions, " the researchers note.

The first trial was a standard phase 1 safety study in 11 normal human

volunteers using 2 doses (1 mg and 5 mg) of the heteropolymer; the drug

was shown to be safe. The second was a phase 1 trial in 6 patients with

SLE that, in addition to evaluating safety, examined clearance of

autoantibodies to dsDNA after a single intravenous administration of 5

mg of ETI-104.

ETI-104 rapidly bound to erythrocytes in both the healthy volunteers and

the lupus patients, and in the lupus patients there was a rapid

reduction in plasma levels of dsDNA autoantibodies 15 minutes after

administration, with a mean antibody reduction of 56% (range 43% to

66%). At 28 days, significant decreases in autoantibodies to dsDNA were

maintained in 3 lupus patients, while in the other 3 the values had

returned to baseline levels.

Because ETI-104 is a murine antibody, Elusys Therapeutics is now

developing a second-generation product, ETI-201, an improved lupus

heteropolymer that uses a deimmunized human chimeric antibody to reduce

immunogenicity of the drug.

Iking-Konert go on to discuss whether there is a role for lowering dsDNA

antibodies in lupus, as they say that some experts have disputed the

idea that this form of treatment could be effective.

But, they add, last year an FDA advisory committee decided that

anti-dsDNA antibodies are a biomarker for disease activity in lupus and

that the FDA is considering the measurement of anti-dsDNA antibodies as

part of accelerated approval for SLE drugs. " This opinion adds to our

belief that further investigations of antigen-based heteropolymers as a

potential treatment for SLE are warranted. "

Future studies will focus on multiple-dose treatment regimens to

evaluate the efficacy of ETI-201 to keep antibody titers low and improve

kidney function in lupus patients, Elusys Therapeutics says.

Source

king-Konert C, Stocks S, Weinsberg F, et al. First

clinical trials of a new heteropolymer technology agent in normal

healthy volunteers and patients with systemic lupus erythematosus:

safety and proof of principle of the antigen-heteropolymer ETI-104. Ann

Rheum Dis 2004; 63:1104-1112.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org