CNTO-148 Demonstrates Efficacy for RA

[Guest guest]

ACR: CNTO-148 Demonstrates Efficacy for RA

Review

SAN DIEGO, Nov. 18 - CNTO-148 (golimumab), an investigational

biologic for once monthly subcutaneous injection, may reduce signs

and symptoms of rheumatoid arthritis (RA) in patients who are

maintained on stable dosing of methotrexate.

That positive finding from a dose-finding study suggests that the

drug may be a good alternative to Remicade (infliximab), which is

made by & , the company that is developing golimumab,

researchers reported at the American College of Rheumatology meeting

here.

In a double-blind, placebo-controlled, 172-patient Phase II trial,

CNTO-148 was shown to reduce the signs and symptoms of RA in

patients also getting methotrexate at 10 mg/week. The trial met its

primary endpoint, which was a statistically significant ACR response

in all the CNTO-148 doses combined, plus a statistically significant

ACR20 response in at least one specific dose. The tested doses were

biweekly 50 and 100 mg doses or 50 and 100 mg every four weeks.

Investigators reported no unexpected adverse events.

The median trough levels of CNTO-148 were all reported to be above

the minimal clinically effective level. This was expected because in

animal studies CNTO-148 was 2.5 to four times as potent as Remicade.

The researchers offered three explanations for the added potency

with golimumab:

CNTO-148 binds more tightly to TNF receptors;

It binds to a different TNF epitope;

And, it is a fully human antibody, which they speculated would make

it much less immunogenic as well.

Nonetheless, not every dose had a statistically significant effect

on ACR20, which one investigator said may reflect a methodological

problem because any patient whose methotrexate or prednisone dose

was increased was counted as a non-success. " That happened even

though patients were doing well, " he said.

Moreover, the placebo ACR20 rate was 37.1%, which was unexpectedly

high. The ACR20 rate for the 50 mg biweekly dose was 50% and for the

100 mg biweekly dose the ACR20 rate was 79.4% (which was significant

compared to placebo P<0.001). The ACR20 rate for the once every four

weeks dosing regimen was 62.9% (P=0.031) and 55.9%, respectively for

the 50 and 100 mg dose. The average response for all doses was 62%

and that was significant (P=0.008).

None of the doses tested was statistically significant in all three

measurements -- ACR20, ACR50, and ACR70, so there was no clear dose

response curve.

Only once-monthly dosing will go forward in the Phase III trial,

which is expected to start in December, but both 50 mg once monthly

and 100 mg once monthly will be tested.

A CNTO-148 investigator, Matteson, M.D., a rheumatologist at

the Mayo Clinic, predicted that CNTO-148 will replace Remicade for

treatment of RA. " Remicade may still have a role, for example in

forms of inflammatory bowel disease where Enbrel [(etanercept),

another anti-TNF biologic which binds TNF alpha], is not effective

but Remicade is, such as Crohn's disease. "

If CNTO-148 eventually wins FDA approval, clinicians will have a

dizzying array of anti-TNF therapies for RA. That's all to the good,

according to Kay, M.D., of Harvard Medical School, who was

principal investigator of the trial. " Not all patients will respond

to every biologic therapy, " he noted. " There are patients who don't

respond to Enbrel who respond to Remicade and vice versa, and there

are patients who don't respond to either. "

Dr. Matteson added, " For me, I think this would be the first-line

drug (in RA) because it is fully human, convenient, and so far has

shown good efficacy and safety. "

Rheumatologist Keystone, M.D., of the University of Toronto,

said, " It's good. It works well. There are no antibodies, so it is

less immunogenic, but we won't know for sure until we do the Phase

III trial. "

http://www.medpagetoday.com/Rheumatology/Arthritis/tb/2185

[Guest guest]

This sounds very promising. Once monthly injections would be easier

than twice a week.

Sue

On Thursday, November 24, 2005, at 04:21 AM, wrote:

> ACR: CNTO-148 Demonstrates Efficacy for RA

> Review

> SAN DIEGO, Nov. 18 - CNTO-148 (golimumab), an investigational

> biologic for once monthly subcutaneous injection, may reduce signs

> and symptoms of rheumatoid arthritis (RA) in patients who are

> maintained on stable dosing of methotrexate.