By David N. Leff
Some sufferers bad-mouth their discomfort as ¿sniffilis.¿ Most physicians ¿ including those who advise ailing patients to ¿take two aspirins and call me in the morning¿ ¿ call the common cold by its clinically correct name, acute rhinitis.
This medical moniker evokes the rhinovirus, perpetrator of about half of all common colds. Its co-conspirator, the body¿s immune system, reacts to the viral infection by triggering a cold¿s familiar symptoms ¿ congested or runny nose, sneezing, coughing.
Those symptoms evoke pharmacy shelves full of over-the-counter cold remedies ¿ from antihistamines and cough relievers to nonsteroidals and decongestants. Reflecting the fact that the common cold is the most common of all infections afflicting humankind, those shelves carry five times as many cold drugs as the runner-up category ¿ vitamins.
But so far there¿s no safe and effective antiviral compound to fight off the rhinovirus. For one thing, the virus deploys, by last count, 102 serotypes (antigenic targets) on the cold¿s pathogenic rap sheet. But rescue may be at hand. All those cold-causing viral types have one thing in common: They infect people by adhering to the epithelial cells lining the nostrils. In 90 percent of them, this stickiness is the work of intercellular adhesion molecules ¿ ICAMs.
That molecule¿s other gig is to act as the docking port for rhinovirus. The discovery of ICAMs in 1984 led scientists at Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), of Ridgefield, Conn., in 1994 to create a recombinant duplicate of that ICAM-1 receptor¿s five extracellular portions. They bind the virus and decoy it away from zeroing in on and infecting the nostrils.
This concept is analogous to attempts, so far unsuccessful, at blocking the HIV¿s receptor molecule, CD4.
After preclinical studies of the product, named tremacamra, the company mounted the first clinical trial of its putative cold-stopper. A paper in today¿s Journal of the American Medical Association (JAMA), dated May 19, 1999, reports the blinded, randomized, placebo-controlled study and its implications. Its title: ¿Efficacy of tremacamra, a soluble intercellular adhesion molecule 1 [ICAM-1] for experimental rhinovirus infection.¿
The trial enlisted 198 volunteers at two university communities, the Medical University of South Carolina in Charleston and the University of Virginia Health Sciences Center in Charlottesville. The article¿s two principal authors, clinical virologists Ronald Turner at Charleston and Frederick Hayden in Charlottesville, both are consultants to BIPI.
In each city, the subjects, ages 18 to 60, and representing an ethnic cross-section, were isolated in individual hotel rooms for the first eight days of the trial. There a random half of them received nasal inhalations of tremacamra in either liquid or powder form. The other cohort got an assortment of placebos. All of these formulations were administered six times a day at three-hour intervals.
They were followed or preceded by a viral challenge consisting of nose drops containing a virulent rhinovirus strain. The solution and powder formulations of tremacamra each were evaluated in preinoculation and postinoculation challenge studies.
On the eighth day, all participating subjects were released from hotel isolation, but continued to monitor their daily cold-symptom status for two more weeks. Then, on day 21, they received a final dose of tremacamra or placebo. Three weeks later, on day 42, the participants contributed serum samples for detection of anti-tremacamra antibodies. (All volunteers received monetary compensation for their participation.)
In logging their rhinitis infections twice daily, subjects judged the severity of eight hallmark cold symptoms ¿ sneezing, rhinorrhea (nasal discharge), nasal obstruction, sore throat, cough, headache, malaise and chilliness. Another measure of cold severity, the weight of nasal mucus, was measured by supplying each participant with preweighed packets of nasal tissues.
In the final analysis, 81 of 177 subjects received tremacamra, of whom 69 (85 percent) got infected with the challenge virus. Of the 96 on placebo, 88 (92 percent) acquired the infection. In both tremacamra and placebo cohorts, half or fewer reported transient adverse events, mainly headache or nasal irritation.
¿Administration of soluble ICAM tremacamra,¿ Hayden told BioWorld Today, ¿did not reduce overall infection rate, but it did significantly affect viral replication, as reflected by reduced nasal viral titers, and also moderated the frequency and severity of colds. The overall frequency of colds¿ he went on, ¿was reduced from 67 percent in the placebo group down to 44 percent in the tremacamra recipients, and the severity of illnesses was reduced by about half. So that there was both an antiviral and clinical benefit recognized.¿
Unanswered Questions Will Go Unanswered
Among its conclusions, the JAMA paper commented, ¿The effect of tremacamra on the symptoms of rhinovirus colds compares favorably with other common cold therapies.¿ But it also observed, ¿It remains to be determined whether treatment with soluble ICAM-1 after the onset of symptoms will have a beneficial effect on viral replication and illness.¿
In an editorial titled ¿Closer to a cure for the common cold?¿ that accompanied the JAMA paper, infectious disease specialist Kenneth McIntosh, of Harvard Medical School, cited several still-open caveats: Will repeated tremacamra administration elicit toxic effects? While sophisticated diagnostic technologies can distinguish between rhinovirus and other cold pathogens, ¿it is unlikely that these tools would be practical for outpatient or office use in the near future.¿
McIntosh concluded: ¿The next step will be determining whether tremacamra can be used to treat symptomatic rhinovirus infection or to prevent clinical colds in the field.¿
That step will not be taken in the indefinite future.
Pamela DeMala, public affairs director at BIPI, told BioWorld Today that the company has ¿put future development of this product [tremacamra] on hold.¿
A company statement noted: ¿Tremacamra, a product designed to alleviate or suppress cold symptoms when sprayed into the nose prophylactically or at the first sign of symptoms, has been shelved indefinitely, following . . . critical analysis of a number of new and promising drug therapies in the Boehringer Ingelheim pipeline.¿