Antibody products in RA trials: IL-15 continues, but CD4 dropped

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Oct 1, 2002

Industryflare

Antibody products in RA trials: IL-15 continues, but CD4 dropped

Copenhagen, Denmark The small Danish biotech company Genmab has reported on

the progress it is making with 2 humanized monoclonal antibody products that

it is developing for the treatment of rheumatoid arthritis. Both offer a

novel approach to the treatment of this condition, but only 1 appears to be

successful. A phase 1/2 trial with HuMax-IL15 was positive, but a phase 2

trial with HuMax-CD4 was negative, and this product will not be developed

further for RA.

HuMax-1L15, being developed jointly with Amgen, targets and binds to

interleukin-15 and is being investigated in psoriasis and Crohn's disease in

addition to RA. According to Genmab, laboratory studies have shown that

IL-15 appears early in the cascade of events that ultimately leads to

inflammatory disease, and preclinical studies have shown that IL-15 induces

both the production of TNF-alpha as well as the recruitment of inflammatory

T-cells. These T-cells in turn promote the production of more IL-15, and the

cycle escalates.

The positive RA study involved 30 patients who had failed to respond to

disease-modifying arthritis drugs (DMARDs), of whom 6 received placebo and

the rest received 1 of 6 doses of the antibody, ranging from 0.15 mg/kg to 8

mg/kg. After a safety evaluation, 23 patients continued to receive the

antibody once weekly for 4 weeks. The company reports that 61% of patients

achieved an ACR20, 39% reached ACR 50, and 26% attained an ACR70.

" In my clinical experience, these ACR scores are impressive and form a good

basis for a phase 2 with HuMax-IL-15, " says Dr n , a member of

Genmab's scientific advisory board, who will join the company shortly as

medical director, rheumatology.

Shares plummeted on announcement

The other product, Hmax-CD4, will not be developed further for RA, and no

more patients will be recruited into a phase 3 trial in RA patients that had

already started or into another ongoing phase 2 study. This was the

company's lead product candidate, and shares plummeted by 56% after the

announcement. Genmab is continuing, however, to investigate this product for

moderate to severe psoriasis.

The negative RA study involved 155 RA patients, divided into a placebo arm

and 4 active groups taking various doses of HuMAX-CD4 (ranging from 20 mg to

240 mg once weekly) plus methotrexate. At 4 weeks, there were no significant

differences between the groupsACR20 responses were achieved by 24% of

patients in the placebo group, compared with between 11% and 29% in the 4

active dose groups.