TOPIGEN Pharmaceuticals Inc., a clinical-stage biopharmaceutical company focused on innovative respiratory therapeutics, recently announced results of a Phase 2 14-day study of inhalable TPI ASM8 in patients with asthma. TPI ASM8 utilizes TOPIGEN's proprietary oligonucleotide technology and is unique because it inhibits multiple targets associated with inflammation in asthma potentially enabling broader, but more specific, pharmacological activity with limited systemic availability and a favorable safety profile.
Following a controlled allergen challenge in patients with mild asthma, TPI ASM8 did not demonstrate statistical significance in the primary efficacy endpoint -- late asthmatic response. However, trends were observed on other endpoints that are consistent with statistically significant results observed in an earlier Phase 2 study. In addition, TPI ASM8 continues to demonstrate a favorable safety and pharmacokinetic profile consistent with all prior studies. TOPIGEN plans to continue Phase 2 clinical development of TPI ASM8 with the initiation of a further trial in patients with asthma and additional toxicology studies to support longer-term trials and regulatory agency review.
"We believe that TPI ASM8 has a very compelling clinical profile for the treatment of moderate to severe asthma," said Mark Parry-Billings, Ph.D., Chief Executive Officer of TOPIGEN. "As an inhalable candidate with a well established safety profile, TPI ASM8 offers a significant advantage over other treatments in development for this patient population -- primarily injectable monoclonal antibodies. Importantly, TPI ASM8 inhibits multiple key inflammatory targets which are increasingly the focus of large pharma drug development pipelines. We plan to expand the TPI ASM8 program with the initiation of additional dose-finding studies in the first half of 2009 and we are optimistic that we will be able to define the potential role TPI ASM8 can play in providing much needed treatment options for patients with moderate to severe asthma who do not respond adequately to the current standard of care."
The Phase 2 14-day trial was a randomized, crossover, placebo-controlled allergen challenge study designed to evaluate the effect of TPI ASM8 in patients with asthma. Primary endpoints were safety and late asthmatic response and secondary endpoints included target mRNA knockdown, early asthmatic response and sputum eosinophils. Eosinophils are cells that are recognized as key contributors to the inflammation and airway destruction in all grades of asthma and other allergic diseases.
Eighteen patients enrolled in the study received TPI ASM8. A difference versus placebo in late asthmatic response was not seen and while TPI ASM8 attenuated the rise in sputum eosinophils post allergen challenge by 50%, this difference in comparison to placebo did not achieve statistical significance. TOPIGEN believes that a blunted and variable response to allergen challenge may have impacted the ability to discriminate a treatment effect. TPI ASM8 continued to generate a positive safety profile and was well tolerated with no reported serious adverse events.
Earlier this year, statistically significant positive results from a Phase 2 three-day allergen challenge study of TPI ASM8 were published in the American Journal of Respiratory and Critical Care Medicine. TPI ASM8, at low lung doses, had a significant effect on the late and early asthmatic response and attenuated the rise in sputum eosinophils by 54%, a difference that was statistically significant. Target mRNA was knocked down approximately five fold and was also statistically significant. The drug was shown to be safe and well-tolerated and systemic exposure was minimal following once daily inhalation.
About Inhaled TPI ASM8
TPI ASM8 is based on TOPIGEN's proprietary oligonucleotide technology and is designed specifically to reduce the recruitment and persistence of chronic inflammatory cells and their associated release of cytokines -- all key components underlying the cause of the disease. TOPIGEN's oligonucleotides are distinct from other oligonucleotide approaches in that they are designed specifically to be nonimmunostimulatory. TPI ASM8 targets two distinct cellular pathways involved in allergic airway inflammation by inhibiting the recruitment of allergic inflammatory cells, via an effect on the CCR3 receptor and by reducing the persistence of allergic inflammatory cells via interference with the common beta sub-unit for the receptors of interleukin IL-3, IL-5 and GM-CSF. This pioneering multi-targeted approach of blocking the synthesis of specific receptors with RNA-silencing technology is expected to have advantages over current medications by providing broader, but specific, pharmacological activity with limited systemic availability, in a convenient, inhaled formulation.
Asthma is a chronic inflammatory disease of the airways in which many cells and cellular elements play a role -- in particular, eosinophils, mast cells and T-lymphocytes. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night and/or in the early morning. The inflammation also causes an associated increase in the airway hyperresponsiveness to a variety of stimuli. Symptoms are usually associated with widespread, but variable airflow obstruction that is at least partly reversible with treatment.
TOPIGEN Pharmaceuticals is developing a clinical pipeline of innovative therapeutics for respiratory diseases, including asthma and COPD. The Company's unique, multi-targeted oligonucleotide product candidates have compelling therapeutic profiles that address major unmet medical needs. TOPIGEN's business strategy is to advance products through clinical proof of concept and out-license to partners for commercialization. For more information, visit: www.topigen.com.
SOURCE: TOPIGEN Pharmaceuticals