Serono has high hopes for psoriasis drug

Serono's Raptiva (efalizumab) is the first in a new class of biological treatments for psoriasis that target ICAM-1, a protein on the surface of T lymphocytes that is implicated in at least three processes that underlie the disease: activation of T cells in the skin by antigen-presenting cells (APCs), transfer of T cells from the blood into the dermis and epidermis, and their re-activation by secondary APC exposure.

At the European Society of Dermatology Research in Vienna, Austria, last week, Raptiva was highlighted as a major new treatment option for European patients, who have so far only limited access to the 'biological revolution' in the treatment of moderate to severe diseases that is already starting to take off in the US.

To date, treatments for psoriasis tend to be unpleasant and cumbersome to administer, prone to side effects and of limited efficacy, a picture that is reflected in patient satisfaction surveys which found that up to 80 per cent of psoriasis sufferers are not happy with their treatment.

Treatment is usually administered in a stepwise fashion, starting with simple emollients and topical treatments and graduating to phototherapy with ultraviolet light and systemic treatments such as methotrexate or cyclosporine if there is a poor response to treatment. In the worst cases, patients can be completely housebound, trapped by complicated and lengthy treatment regimens and the stigma associated with a highly visible and debilitating skin disease.

Biologicals such as Raptiva have emerged as alternatives to systemic therapy that offer not only much more convenient treatment - a single weekly injection in the case of Serono's drug - but also improved efficacy and fewer side effects.

Kim Papp of the University of Western Ontario in Canada, a specialist in the treatment of psoriasis, told the meeting that the disease is surprisingly common - affecting one out of every 50 people worldwide - and that 25 per cent of those affected have moderate to severe disease that would make them potentially eligible for biological therapy.

Serono presented the first 30-month data from the ongoing CLEAR study at the ESDR meeting - revealing that 30 per cent of patients had a greater than 75 per cent improvement in psoriasis - measured by the psoriasis area and severity index (PASI) score system.

This level of efficacy compares favourably with current systemic therapy. Moreover, the rate of adverse events was not significantly different to control. At present, systemic psoriasis drugs are associated with a significant side effect burden. Half of the patients receiving Raptiva saw a 50 per cent improvement in PASI.

Competitive position​

But Raptiva is not the only biological therapy on or near the market, at least in the US. There, Biogen can claim first to market position with Amevive (alefacept), another T cell-targetting therapy that acts by destroying the lymphocytes associated with the disease. Raptiva is sold by Genentech and Xoma in the US.

Aside from these two agents, various drugs targeting a cytokine produced by T cells and implicated in psoriasis - tumor necrosis factor alpha - are also emerging. These include Wyeth's Enbrel (etanercept), Johnson & Johnson's Remicade (infliximab) and Abbott's Humira (adalimumab), all of which are already used to treat rheumatoid arthritis. Serono is also developing an anti TNF biologic called onercept, which is currently in Phase II testing.

In Europe, Raptiva has been recommended for approval by the EU's Committee for Medicinal Products for Human Use and could be approved and launched in its first markets in October. In markets such as a France where pricing negotiations are required, the introduction will more likely be early next year.

Meanwhile, Enbrel was also recommended for approval in psoriasis earlier this year, and is on course to be the first anti-TNF drug cleared for this indication. Biogen's Amevive was surprisingly turned down by the EMEA last year, despite being cleared in the US. The agency is demanding head-to-head trials with approved therapies - such as cyclosporine, methotrexate or oral retinoids - before it will back the drug.

A spokesman for Serono said that while anti-TNF drugs are clearly effective, they have side effects - including demyelination, congestive heart failure and reduced resistance to tuberculosis. This suggests the anti-T cell therapies such as Raptiva should be used first-line, if a biologic therapy is being considered.

But despite its promise, Raptiva and other biologicals cannot help every patient. For example, around 25 per cent of patients in the CLEAR study had no response at all to Raptiva, and Serono now has a pharmacogenetic programme ongoing trying to determine the genetic profile of responders versus non-responders.

It is estimated that at least six genes are involved in the disease, with the disease occurring once a patient is immunologically primed and a trigger event - such as an infection - takes place. Once it emerges, patients have psoriasis for life.

Looking further back in the pipeline, Serono is continuing to conduct basic research in psoriasis, and one focus is on the use of agents that bind DNA and switch off the disease.

Finally, there is the difficult issue of cost. In the US, Raptiva is priced at around $14,000 a year, so its use is likely to be reserved for those patients whose lives are significantly and severely impacted by the disease. A study published last year by Steven Feldman, a professor of dermatology at Wake Forest University School of Medicine, found that methotrexate costs about $1,600 a year and phototherapy from $3,600 to $4,600, with cyclosporine coming in a little higher. In contrast, biologics range from $16,000 to $33,000 a year.

This has been reflected in the sales of the drug in the US. At one point tipped as a potential billion dollar drug, analysts have scaled back their expectations to the $300-$500 million range, at least in the short-term, as they believe it is likely to be used after the more established therapies. This pattern is likely to be the same for all biologics.

Raptiva has seen somewhat slow take-up in the US - expected as doctors get accustomed to using the new drug - but it still brought in revenues of just under $20 million in the first half of the year in the US alone.