Reslizumab(CINQUIL) is a humanized monoclonal antibody
targeted against IL-5 that is being developed by Cephalon for the
treatment of eosinophilic asthma. In September 2010, Cephalon
indicated that it hopes to file a BLA in 2013, focusing on this subset of
severe asthmatics. Such patients are ca. 30% of the asthmatic population,
with the 750,000 patients in the United States suggested to offer the potential for peak market sales of $1 billion. However, previous
attempts to develop recombinant IL-5 antagonists for the treatment of asthma saw very disappointing clinical results with both mepolizumab
(GlaxoSmithKline) and reslizumab (Schering-Plough and Celltech).
Schering-Plough (now Merck) had been developing reslizumab in
partnership with Celltech (now UCB), utilizing the latter’s antibody
technology, but terminated development in 2002 after disappointing
clinical results. The rights were acquired by Ception Therapeutics in
2007, with development reinitiated for both pediatric eosinophilic
esophagitis and eosinophilic asthma. Cephalon acquired an option to
acquire Ception in January 2009 and exercised this option in April 2010
despite unpromising results in the Phase II/III study of reslizumab in
pediatric eosinophilic esophagitis patients.
In its November 2009 R&D presentation, Cephalon presented data
(from Schering-Plough) showing that reslizumab treatment of asthmatics
results in a sustained suppression of eosinophil levels; the protocols
employed in the Phase II/III study in pediatric eosinophilic esophagitis
and a Phase II study in eosinophilic asthma were described. The Phase
III study in asthmatics has yet to commence, but a 190-patient openlabel Phase III extension study in eosinophilic esophagitis is ongoing.
The Phase II/III study showed no discernable symptom improvement
despite suppression of eosinophil levels at all three doses tested (see
Walsh 2010).43 The outcome of the 106-patient Phase II study, in
February 2009, in asthmatics prompted Cephalon to acquire Ception.
Reslizumab treatment produced significant improvement in lung
function and reduced airway inflammation.
Reslizumab is currently the most advanced of three anti–IL-5monoclonal antibodies in development, but the 2013 submission date for a BLA seems optimistic given that Phase III studies have yet to start.
Mepolizumab is now in Phase II studies for the treatment of severe
asthma and nasal polyposis (having previously been filed for approval
in Europe for the treatment of hypereosinophilic syndrome), but the
filing was withdrawn and development for that indication discontinued
in late 2009. MedImmune and Kyowa Hakko Kirin’s benralizumab has
successfully completed a Phase IIa study in asthma with data presented
in September 2010, and a 108-patient study in asthma was completed
in October 2010. A similar-size Phase II study in COPD commenced in
Reslizumab is a humanized monoclonal antibody intended for the treatment of eosinophil-meditated inflammations of the airways, skin and gastrointestinal tract. As of September 2009, the drug is undergoing Phase II/III clinical trials.
Eosinophils are important proinflammatory cells that make a major contribution to the inflammation seen in allergic diseases including asthma. Interleukin-5 is central to eosinophil maturation, release from the bone marrow, and subsequent accumulation, activation, and persistence in the tissues. Reslizumab (Cinquil™) is a humanized monoclonal antibody with potent interleukin-5 neutralizing effects, which represents a potential treatment for poorly controlled eosinophilic asthma. This review will consider the current status of the clinical development of reslizumab for asthma and in other inflammatory diseases with a marked eosinophilic component.