SAN DIEGO - Biotech drugs have the potential to address unmet medical needs if physicians, patients and payers can accept their risk/benefit ratios and pricing, according to discussion at the 2007 Annual Meeting of the American Academy of Allergy, Asthma and Immunology.

In the asthma space, big pharma brands like Merck & Co. Inc.'s Singulair (montelukast sodium) and Schering Corp.'s Claritin (loratadine) already have been forced to share the spotlight with biotech drugs like Xolair (omalizumab, Genentech Inc. and Novartis AG), which brought Genentech $425 million in revenues in 2006. Yet Christopher Brightling, of the University of Leicester, UK, reported data from a survey of severe asthmatics in which 44 percent said at least one activity in their lives was "totally or very limited" by asthma, indicating a remaining unmet need. He pointed to tumor necrosis factor (TNF) inhibitors as a potential answer for these patients.

TNF inhibitors such as Enbrel (etanercept, Amgen Inc. and Wyeth Pharmaceuticals Inc.) and Remicade (infliximab, Centocor Inc.) were two of the top-selling drugs in 2006, bringing in $4.4 billion and $4.3 billion, respectively. Their success is at least partly due to their applicability in treating a broad range of diseases: Enbrel is approved in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and psoriasis, while Remicade can claim all of those, as well as Crohn's disease and ulcerative colitis.

Severe and refractory asthma patients, in whom TNF appears to be particularly up-regulated, could offer a significant additional market for those drugs. Brightling presented results from several studies of Enbrel and Remicade in that indication, some of which demonstrated dose-dependent improvement and others of which showed less of an effect. He concluded that future studies will need to be "carefully designed because giving the wrong patients the treatment may miss its potential benefit." Brightling also cautioned that the risk/benefit ratio for patients must be considered in such trials, as anti-TNF drugs can cause serious side effects such as infections and lymphomas.

Risk/benefit ratios also came up in a session on allergic rhinitis. Here again, although many drugs like antihistamines and intranasal steroids are approved for the condition, 20 to 30 percent of patients are "still suffering" and offer an unmet need, said Tushar Shah, senior vice president and scientific and clinical development with Altana Pharma U.S.

While some companies like UCB Inc. and Inspire Pharmaceuticals Inc. are hoping to meet that need with their own versions of antihistamines for allergic rhinitis, other biotechs are looking at novel approaches. Isis Pharmaceuticals Inc. is conducting preclinical studies with a second-generation antisense drug that inhibits the interleukin 4 receptor's alpha subunit. Coley Pharmaceutical Group Inc. and partner Sanofi-Aventis Group are in Phase I with a toll-like receptor approach.

And then there's Dynavax Inc., which reported last month that efficacy results from a Phase III trial of immunostimulatory drug Tolamba could not be measured due to a low level of ragweed-specific allergy observed in the trial. That news sent the stock down 30 percent, and a presentation at AAAAI regarding benefit in a predefined subset of Midwestern patients did not help it recover. (See BioWorld Today, Jan. 9, 2007.)

Howard Druce of New Jersey School of Medicine questioned whether payers will support the higher prices biotech drugs must charge to recoup the risk and expense of developing novel therapies, particularly in a field where there are so many existing treatments nearing generic status.

"Look at the treatment effect demonstrated by Xolair and Claritin," he said. "Which do you want to pay for?"

Shah also raised the question of safety when dealing with drugs that are administered systemically, like the newer biotech approaches. "When you get into systemic administration, you are dealing with unknowns, and how much risk can you take when there are already safe and effective treatments available?" he asked.

The risk theme came up yet again in a discussion of T-cell co-stimulation. Flavio Vincenti, of the University of California in San Francisco, discussed the disastrous outcome of TeGenero AG's Phase I trial of co-stimulatory antibody TGN1412, which sent all six European patients dosed to the hospital. Yet he pointed to concerns about clinical conduct standards in the TGN1412 trial and emphasized the potential of other co-stimulatory drugs like Orencia (abatacept) and belatacept, both from Bristol Myers Squibb Co.

Looking to the future, Vincenti said he'd like to see combinations of drugs, such as belatacept with other T-cell modulators like Raptiva (efalizumab; Genentech) or B-cell modulators like anti-CD40 monoclonal antibodies. During a discussion of B-cell therapies, E. William St. Clair of Duke University Medical Center also said he'd like to see more combinations in the future, particularly of an anti-CD19, anti-CD20, anti-CD22 or anti-CD40 antibody with a drug targeting B-cell survival factors such as BAFF or BLyS.