By Kim Coghill
Genmab A/S has been given FDA clearance to start Phase III studies of its rheumatoid arthritis injection that was described as a unique monoclonal antibody by the company¿s CEO, who said the drug eventually could generate upwards of $1 billion annually in U.S. sales alone.
In this first round of Phase III testing, HuMax-CD4 will be studied in patients suffering from active rheumatoid arthritis (RA) who have not responded to other treatments.
¿We are going to treat the patients who have nothing available to them,¿ Lisa Drakeman, president and CEO of Copenhagen, Denmark-based Genmab, told BioWorld Today. ¿By the time these patients fail TNF-a blockers and methotrexate, there¿s nothing left, so this is an urgently needed new medical product.¿
Enrollment of the 400-patient, 50-site study will begin immediately. The complete study, including analysis, is expected to run into 2003, and if all goes well, Drakeman said HuMax-CD4 potentially could enter the market in 2004.
She said an estimated 500,000 U.S. RA patients are not responding to other treatments.
¿Genmab has moved HumMax-CD4 from Phase I/II to Phase III in under two and a half years,¿ Drakeman said. ¿This is a credit to our highly experienced clinical development team and their ability to work collaboratively with the FDA.¿
Nearly 2 million U.S. patients, and about 1 percent of the world¿s population, suffer from some level of RA. With that market in mind, Genmab has no intention of limiting HuMax-CD4 to patients who have failed other treatments. Indeed, upon completion of the 400-patient trial, the company will initiate a larger Phase III trial for an expanded use in patients with moderate to severe RA.
And Genmab is not the least bit intimidated by its competition in the RA field that includes the recently approved Kineret, made by Thousand Oaks, Calif.-based Amgen Inc.; New Brunswick, N.J.-based Johnson & Johnson¿s Remicade; and Seattle-based Immunex Corp.¿s Enbrel.
That¿s because HuMax-CD4 acts differently than other products on the market, Drakeman said.
¿HuMax-CD4 works by blocking the CD4 receptor on T cells ¿ it¿s an early stage in the inflammation cascade ¿ and it precedes, for example, the release of TNF-alpha or the release of IL-1 [interleukin-1],¿ Drakeman said. ¿And another thing, if you look at animal studies where they test agents in combination, if you add a CD4 antibody to any of the other antibodies like a TNF-alpha antibody, you get a synergistic response. You get a better response than you would for either of the products alone, so that also shows this is clearly a different mechanism of action.¿
The 400-patient Phase III study is designed to confirm the safety and efficacy of HuMax-CD4 in RA patients. Participants will be given either 80 or 160 milligrams of HuMax-CD4 or placebo for 26 weeks.
HuMax-CD4 will be administered by subcutaneous injection, but Drakeman said eventually patients would be able to give themselves a monthly shot.
¿Based on everything we know about the science and about responses and safety to date, HuMax-CD4 should interrupt the inflammation process, so it isn¿t just to take pain away, it is to interrupt the disease,¿ Drakeman said. ¿For this study we want to improve the signs and symptoms of the disease. For upcoming studies we will not only look at signs and symptoms, but we will also see if we are halting disease progression.¿
In Phase I/II studies, HuMax-CD4 was safe and well tolerated, the company said.
Also, the product is in Phase II studies for use in psoriasis patients. The company recently released initial results from a psoriasis study showing a statistically significant dose response in doses up to 160 mg. Furthermore, mean Psoriasis Area Severity Index scores were reduced in all treatment groups, with a 30 percent difference between the placebo and 160-mg dose groups.
Princeton, N.J.-based Medarex Inc. granted Genmab exclusive North American rights to HuMax-CD4, which was created using Medarex¿s UltiMAb Human Antibody Development System. Medarex owns about 33 percent of Genmab¿s stock.