“The first new drug treatment for asthma for more than a decade has dramatically reduced the symptoms in sufferers and could help hundreds of thousands of patients in Britain with the disease,” reported The Independent . The newspaper said that preliminary trials of a new drug, called pitrakinra, showed that it reduced breathlessness by about three times compared with placebo, when people with allergic asthma were exposed to triggers such as house dust or cat hairs.
The story is based on a small, preliminary clinical study that provides the first evidence from human studies of the beneficial effects of this drug. More testing of the drug’s safety and larger studies aimed at defining the groups of patients who will benefit most from the drug, will be required as the drug progresses along the path to being fully available.
Where did the story come from?
Dr Sally Wenzel from the University of Pittsburgh in Pennsylvania, and colleagues at the Guy’s Drug Research Unit in London and working for Aerovance Ltd (the biopharmaceutical company based in California who make the drug) conducted the study. The investigators were either employed by, contracted, or acted as consultants to Aerovance, who funded the study. It was published in the peer-reviewed medical journal The Lancet .
What kind of scientific study was this?
This was a report of two randomised, phase 2a, clinical trials of the experimental drug, pitrakinra. Pitrakinra is a drug that can interfere with the actions of the chemicals (interleukin 4 and 13) in the lungs that play a part in the normal response to an allergic asthma “trigger”. Allergic asthma is caused by the exposure to a trigger (such as cat hairs, house dust or experimental chemicals), and this that cause two responses. Firstly, there is an early (acute-phase) response, which generally stops the asthma attack quickly and breathing returns to normal within 30–60 minutes. In a certain group of patients, the early response is followed by a second, delayed drop in lung function two to 12 hours after the exposure to the trigger. The researchers were monitoring the change in this second, late response.
Both studies tested the ability of the drug to block the effects of a challenge with a trigger substance. In the first study, 24 patients were randomly allocated to receive either an injection of the drug, pitrakinra, or a placebo injection. Neither the patient nor the investigators knew which injection had been given. The patients were assessed before the injection and at four weeks afterwards. Lung function was measured by how freely they could breathe out (this is called the forced expiratory volume expired in one second or FEV1) after they had been given an asthma trigger to inhale (called a challenge). Normally, allergic people would become mildly breathless after this type of challenge, causing a reduction in the amount of air they could breathe out and therefore a drop in FEV1; often they would also require medication. The researchers measured the effectiveness of the drug by monitoring the lowest FEV1 that was recorded four to 10 hours after the challenge during the second, delayed response to the challenge.
In the second study, 36 patients were also randomised but were given the drug or placebo as an inhalation through a nebuliser. The average percentage decrease in FEV1 four to 10 hours after the challenge was then recorded.
What were the results of the study?
All patients completed the first study but three patients (two from the placebo group and one from the active group) dropped out and were excluded from the analysis of the second study.
In the first study, there was greater maximum percentage drop in FEV1 after challenge in the group given placebo (23.1% ) compared with the group who were using pitrakinra (17.1%), although the difference (6%) was not statistically significant. In the second study, there was a greater percentage drop in average FEV1 in the placebo group (15.9%) than in the group who were using the pitrakinra inhalations (4.4%); this three-fold difference was statistically significant.
What interpretations did the researchers draw from these results?
The researchers conclude that “local treatment, targeted at … the lung, could substantially diminish the symptoms of asthma.”
What does the NHS Knowledge Service make of this study?
These two small phase two studies appear to be well conducted and reported. Despite the small number of patients involved, a significant late protection against the challenge has been demonstrated for the inhaled drug and a trend towards the same result for the injected form of the drug. Other biochemical tests and the results of questionnaires regarding adverse effects also support the mechanisms of action established in the pre-clinical (animal studies) of this drug, and provide the first data on its safety. The results of this study only apply to people with an allergic type of asthma: that is those who have shown a reaction to pet hairs or house dust mite on skin testing.
As the researchers say, “Future studies of this drug … in asthmatics of all levels of severity over longer periods of time are clearly warranted.”
Sir Muir Gray adds...
This looks promising and will be a focus of interest for the next five years as the research develops.