Biogen Idec's Baminercept Alfa Shows Promise In Patients With Rheumatoid Arthritis

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Biogen Idec's Baminercept Alfa Shows Promise In Patients With Rheumatoid

Arthritis

Main Category: Arthritis

Also Included In: Clinical Trials / Drug Trials

Article Date: 14 Jun 2008

http://www.medicalnewstoday.com/articles/111181.php

Biogen Idec presented data on baminercept alfa (BG9924, LTBR-Ig), the first

dual-mechanism, lymphotoxin-B; (LT-ß and LIGHT pathway inhibitor in

development for the treatment of autoimmune diseases, including rheumatoid

arthritis (RA), during the 2008 European League Against Rheumatism (EULAR)

Annual European Congress of Rheumatology at the Le Palais de Congress de

Paris.

Three abstracts were presented, including one podium presentation

highlighting the Phase IIa preliminary safety and efficacy data as well as

two poster presentations. The Phase IIa data suggest baminercept alfa is

well tolerated. DAS, EULAR and other efficacy measures were improved in

patients receiving baminercept alfa vs. patients receiving placebo and

persisted up to eight weeks after the final baminercept alfa injection.

Podium presentation * " Preliminary safety and efficacy of Baminercept alfa

(BG9924, LTBR-Ig) in the treatment of rheumatoid arthritis " - (Presentation

OP-0122 )

Poster presentations * " Long-term safety assessment of Baminercept alfa

(BG9924, LTBR-Ig) in Cynomolgus monkeys - (Poster FRI0156) * " Treatment of

cynomolgus monkeys with Baminercept alfa (BG9924, LTBR-Ig) results in

modulation of a specialized vasculature implicated in lymphocyte trafficking

to areas of chronic inflammation " = (Poster SAT0040 )

" We are excited to take part in the Annual European Congress of Rheumatology

and to share promising results for baminercept alfa, " said Ajay Nirula,

Director of Medical Research at Biogen Idec. " We are committed to developing

new treatment options for those living with RA and are encouraged that

results from the Phase IIa study suggest that innovative targeting of a new

pathway may be effective in treating this disease. "

Phase IIa Data Results

The Phase IIa blinded, multicenter, placebo-controlled trial was designed to

assess the safety, pharmacokinetics, pharmacodynamics and efficacy of

baminercept with methotrexate, a standard RA therapy, at different dose

ranges. Patients (n=47) were randomized in a dose-escalating fashion to

receive placebo or one of six doses of baminercept, ranging from 0.01 mg/kg

to 3.0 mg/kg once weekly for four weeks, followed by eight weeks of

observation. Patients had to have received methotrexate for at least three

months prior to enrollment and continued to receive a stable dose of

methotrexate throughout the study period.

Study results suggested improvement in the majority of ACR core set

measurements (a series of standard measurement criteria for RA symptom and

disease improvement) in patients given baminercept compared with placebo. At

day 35, patients given baminercept showed an average 60 percent improvement

from baseline in swollen joint count and 47 percent improvement in tender

joint count, compared with 4.6 percent and 6.7 percent with placebo,

respectively. Improvements in these ACR measures persisted for eight weeks

after the final baminercept dose. Similar levels of improvements were

observed at day 35 in several other standard markers of inflammation and

disease progression. ACR scores and other measures improved in a dose

dependent manner, with the greatest improvements reported in the groups

receiving 1.0 mg/kg and 3.0 mg/kg.

The most common adverse event in patients receiving baminercept was

headache. Transient mild-to-moderate flu-like symptoms were observed in 9

patients (25 percent) within 24 hours after the first dose of baminercept.

However, these symptoms responded well to paracetamol (acetaminophen) and

tended not to recur with subsequent doses. No serious, drug-related adverse

events were reported in this study.

Based on the results of the Phase IIa study, Biogen Idec has initiated two

Phase IIb trials to study baminercept alfa in combination with methotrexate

in patients with moderate to severe RA. 1.) the REACT study for patients

with an inadequate response to treatment with DMARD therapy

(disease-modifying antirheumatic drug), which completed enrollment earlier

this year, and 2.) the RESPOND study for patients having an inadequate

response to a TNF inhibitor (biologic therapies that target the TNF

pathway). A decision to enter into Phase III development will be made

sometime towards the end of 2008 pending analysis of the results of Phase

IIb studies.

Rheumatoid Arthritis and the LT-B Pathway

In patients with RA, certain immune cells malfunction and attack the joints,

causing painful and chronic inflammation as well as destruction of

cartilage, tendons and bones. As in other autoimmune diseases, the immune

system mistakes healthy cells for foreign invaders. Though the exact cause

of RA is unknown, new research is uncovering the immunologic and genetic

factors that play important roles in triggering and perpetuating

inflammation of the joints.

As shown in preclinical studies, baminercept alfa is thought to inhibit the

function of LT-B and LIGHT, two critical components of the LT-B pathway

implicated in the progression of RA and other autoimmune diseases. These

molecules are novel members of the TNF superfamily, distinct from TNF-B and

lymphotoxin-B targeted by some biologics indicated for RA. Autoimmune

diseases are in part characterized by the inappropriate emergence of

organized immune cell collections, or lymphoid structures, at sites of

inflammation or in immune system tissues. Baminercept alfa is thought to act

by inhibiting the formation and maintenance of lymphoid structures and the

consequent activation of aberrant immune effector cells implicated in the

pathogenesis of autoimmune diseases such as RA. By blocking inappropriate

signals from cell-surface LT-B and LIGHT ligands, baminercept alfa may help

restore a normal immune environment.

The LT-B pathway was discovered at Biogen Idec, and baminercept alfa is a

wholly-owned Biogen Idec molecule that was discovered in collaboration with

academic scientists. Baminercept alfa is one of several programs in the

company's research and development efforts in rheumatology.

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Article adapted by Medical News Today from original press release.