For a long time, few drugs were developed for rheumatological diseases. It was considered unattractive from a commercial viewpoint since relatively few patients (compared to cardiovascular diseases, for example) suffered from them. It was also thought that this market had little pricing power.
This changed dramatically with biologics such as Etanercept (co-marketed by Amgen (NASDAQ:AMGN) and Wyeth (WYE)) and Infliximab (Centocor, a division of J&J (NYSE:JNJ)). Developed for rheumatoid arthritis [RA] and inflammatory bowel disease [IBD], these compounds changed the treatment paradigm. Much better efficacy was possible, and today these drugs sell in the billions. Rheumatology suddenly became hot. So much so, that one can argue that with anakinra (Amgen), adalimumab (Abbott (NYSE:ABT)), abatacept (Bristol Myers Squib (NYSE:BMY)), and rituximab (Genentech (DNA)), the field of RA therapy may be getting a bit crowded with biologics.
In contrast, systemic lupus erythematosus remains under-treated. This has attracted the attention of a few companies. However, there are hurdles. Some arguments put forward against developing drugs for RA are now being used against lupus – that it is a small market, and that there is no pricing power. There also are clinical issues – the disease is highly variable, with the result that clinical trials are beset with issues related to standardization, endpoints and measurements.
On Tuesday, April 29, Genentech and Biogen Idec (NASDAQ:BIIB) released the top line results of the phase II/III study with rituximab. Already approved for lymphoma and RA, this would have been an interesting line extension. The companies stated that the study did not meet its primary endpoint defined as the proportion of rituximab treated patients who achieved a major clinical response [MCR] or partial clinical response [PCR] measured by BILAG, a lupus activity response index, compared to placebo at 52 weeks. The study also did not meet any of the six secondary endpoints.
The study was fairly rigorous, though it did exclude patients with lupus nephritis. A total of 257 patients from approximately 55 sites (U.S. and Canada) were randomized to receive rituximab plus prednisone or placebo plus prednisone in two infusions 15 days apart. The patients were retreated six months later with the same regimen. Patients were evaluated for efficacy every four weeks for 52 weeks. On the safety side, patients treated with rituximab had a higher incidence of herpes viral infections (15.4 percent with rituximab versus 8.0 percent with placebo), and neutropenia (3.6 percent with rituximab versus 0 percent with placebo).
Needless to say, the results are disappointing. Rituximab is a well-established drug, so this won’t affect the companies involved, though an upside surprise would have been good for them. The biggest losers are patients, who really could use an effective drug. But all is not lost for there are other companies involved in lupus research. For example, La Jolla Pharmaceutical (NASDAQ:LJPC) has conducted a phase III study with abetimus sodium, and was in conducting an additional phase III study in 2007 under the special protocol assessment pathway by the FDA. Human Genome Sciences (HGSI) and Glaxo SmithKline (NYSE:GSK) are conducting a phase III study with belimumab. The 52-week study design and endpoints (SLEDAI instead of only BILAG) are quite different from the Genentech/Biogen Idec study. While the phase II data of these two drugs do not suggest home runs, we will have to see what the phase III studies show.