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CYT005-AllQbG10 met primary and secondary endpoints
Schlieren (Zurich), Switzerland, December 14, 2005 - Cytos Biotechnology (SWX: CYTN) announced today that its open-label phase IIa trial in 20 patients with allergic rhinoconjunctivitis and asthma due to house dust mite allergy met its primary efficacy endpoint, defined as a median ten-fold increase in allergen tolerance upon conjunctival provocation with house dust mite allergen. After 10 weeks of treatment with 300 µg CYT005-AllQbG10 in conjunction with house dust mite allergen, the median allergen tolerance was increased by at least. a factor of 100 (p<0.0001). Post treatment, 17 of the 20 patients were completely tolerant to the allergen challenge. Their symptom scores remained below the predefined minimal threshold level even when the highest possible allergen dose using the undiluted allergen solution was applied as an eye-drop. Of the remaining three patients, two subjects showed an increase of allergen tolerance by a factor of 100, whereas one subject was not available for the provocation tests post-treatment.
CYT005-AllQbG10 also met the following secondary efficacy endpoints: The median score of allergy and asthma symptoms in daily life was reduced from 13 points pre-treatment to 2 points posttreatment (p<0.0001), on a scale from 0-27 points. When assessing the consequences of allergic rhinoconjunctivitis on daily life, such as restrictions due to the disease during work, leisure time, or sleep, the median score was reduced from 3 points pre-treatment to 0 points post treatment (p<0.0001), on a scale from 0-4 points. When assessing the consequences of asthma on daily life, the median score was reduced from 3 points pre-treatment to 0 points post treatment (p<0.0001), again on a scale of 0-4 points. Finally, treatment also led to a statistically significant reduction in reactivity to the allergen in the skin prick test (p<0.001), while reactivity in the unspecific bronchial provocation test with methacholine remained unchanged.
CYT005-AllQbG10 was safe and well tolerated with the expected side effects due to exposure of the patients to the allergen extract during treatment.
PD Dr. med. Thomas Kundig, Head of Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, where the study was carried out, commented: "There is not much more you can expect from a disease-modifying treatment for allergic rhinitis and asthma. All patients we treated with CYT005-AllQbG10 were either completely symptom-free, or have seen a dramatic improvement that eased their lives a lot. This therapy seems to be not only much faster than conventional desensitization but also much more efficacious. We only rarely see such an effect even after three to five years of conventional desensitization, which requires the patient to visit our clinic 50 to 80 times. On average, allergen tolerance is increased only in the range of a factor of 10 after three years of conventional treatment."
Dr. Kündig continued: "A vaccine like this is desperately needed. Allergic rhinitis affects approximately 20% of the industrialized world and frequently progresses to asthma. Controlled studies have shown that desensitization is an effective treatment with a long-term effect for allergic rhinitis, allergic asthma, and allergic reactions from stinging insects. Also, desensitization has been shown to interrupt the expansion of allergic sensitization from a single allergen to multiple allergens and is thought to stop progression from allergic rhinitis to asthma. As symptomatic treatment using anti-histamines and corticosteroids can achieve neither the long-term effects, nor stop progression of disease, desensitization should be the preferred treatment of allergies. However, current desensitization regimens appear to be too time consuming for most people, therefore only few allergy sufferers take advantage of them. A vaccine acting as quickly and effectively as we have seen in this study would without doubt address a major unmet medical need. We certainly look forward to continue working with this extremely promising vaccine candidate."
About allergic diseases
Allergy as a whole is a widespread disease that ranges from hay fever to seriously life threatening forms of asthma and anaphylaxis. According to the World Health Organization, more than 20% of the world population suffers from allergic diseases (WHO, 2002). An allergic reaction in general is caused by hypersensitivity of the immune system to a normally harmless substance, the so called allergen, causing a misdirected, so called Th2 type immune response. Today, three general approaches are being pursued to relieve the symptoms of allergic diseases: avoidance of the allergen, prescription of medication that targets the symptoms of the disease, and specific immunotherapy, also known as desensitization, which is the only disease-modifying treatment available today and which reduces the allergy symptoms over a longer period of time. A typical desensitization therapy, however, can consist of up to 80 allergen injections over three years and is thus time-consuming, costly, and inconvenient for the patient.
About CYT005-AllQbG10
CYT005-AllQbG10 is a therapeutic vaccine in development for treatment of allergic diseases. The vaccine is currently being tested for treatment of house dust mite allergy and grass pollen allergy. CYT005-AllQbG10 is comprised of the ImmunodrugTM carrier QbG10 mixed with the natural allergen extract of choice – house dust mite allergen for this study. QbG10 itself consists of the virus-like particle Qb filled with an immunostimulatory sequence called G10. QbG10 is believed to act as a potent adjuvant enhancing the establishment of a "non-allergic" Th1 type immune response. Th1 type immune responses have been shown to suppress "allergic" Th2 type immune responses. CYT005- AllQbG10 thus aims at induction of such a Th1 type immune response to balance an existing Th2 type immune response. As such, CYT005-AllQbG10 is thought to act as a causal and disease-modifying vaccine to treat allergy.
By combination of the classical desensitization approach with the carrier QbG10, the complete desensitization campaign could be shortened from three years duration to less than three months. This should be much more convenient for the patient and should therefore have the potential to become a more widely used allergy treatment than conventional desensitization. ImmunodrugTM candidates based on QbG10 could likewise be applied to treatment of a wide range of other allergies, when QbG10 is combined with other allergens.
About the phase IIa study
The phase IIa study was an open-label, single arm study in 20 patients with mild to moderate allergic rhinoconjunctivitis and mild asthma due to house dust mite allergy; a type of allergy that afflicts about 50% of all allergic patients (Clin Exp Allergy, 2004; 34:597). The study was designed to evaluate the safety, tolerability and exploratory efficacy of the vaccine and was conducted at the University Hospital in Zurich, Switzerland. Male and female otherwise healthy subjects, aged 18-56 years were included in the study. Upon entry into the study, the allergic status was recorded by the conjunctival provocation test, the skin prick test and by methacholine challenge. Allergy symptoms and impact of disease on daily life during the past two weeks were also recorded. Then, at the first two weekly visits, the allergen was injected subcutaneously and up-titrated. Thereafter, at the next 4 weekly visits, allergen was further up-titrated, but now co-administered subcutaneously with 300 ìg CYT005-AllQbG10. Finally, at an additional two biweekly visits, 300 ìg CYT005-AllQbG10 were coadministered with the highest targeted allergen dose. Two weeks after the last dose, the allergic status of the patients was again assessed using the same allergy tests (conjunctival provocation test, skin prick test and methacholine challenge) and allergy symptoms and impact of disease on daily life were recorded for the last two weeks.
About the analysis
Of 21 enrolled patients, all patients were included into the intent-to-treat analysis who received at least one injection of the study medication CYT005-AllQbG10 (n ). Of these 20 patients, 19 were available for a final visit. For the one individual who dropped out, the baseline values were used for the post-treatment analysis ("baseline-carry–forward").
The conjunctival provocation test is a commonly used test to monitor the allergic status of an individual. Standardized aqueous allergen solutions are applied in the form of eye-drops to the conjunctiva in increasing concentrations (no allergen; dilutions 1/1,000; 1/100; 1/10; 1/1) and the following allergy symptoms are recorded: conjunctival hyperemia, tearing, itching, burning, and swelling of eyelids. Each symptom can be absent (0 points), mild (1 point), moderate (2 points), or severe (3 points). The predefined minimal threshold level (when symptoms are considered to be above background) is reached at 3 of 15 points. The skin prick test measures the skin reaction, consisting of wheal and flare, upon pricking the allergen solution through the skin using a lancette. Using the same increasing allergen concentrations, a threshold concentration can be titrated. The area of the induced local skin reaction is recorded and analyzed. The bronchial provocation test with methacholine is an allergen-independent method of assessing airway responsiveness. In this test, the patients inhale an aerosol of one or more concentrations of methacholine.
For assessment of allergy symptoms during daily life, the following symptoms were recorded: runny nose, clogged nose, periods of sneezing, itchy nose, itchy throat, itchy eyes, red eyes, dry cough, and asthma bronchiale. Each symptom can be absent (0 points), mild (1 point), moderate (2 points), or severe (3 points). The scale ranges from 0-27 points. For assessment of the consequences of allergic rhinoconjunctivitis and asthma on daily life, patients were asked i) whether there were annoying symptoms in daily life, ii) whether there were sleeping disorders, iii) whether activities during work or school were restricted and iv) whether activities during leisure time were restricted. Patients could answer each of the four questions with yes (1 point) or no (0 points), the scale ranging from 0-4 points.
. This value remains open-ended, since post-treatment 17 patients did not reach the minimal symptom score at any dose.
Conference Call
In combination with its R&D day presentation 2005, Cytos Biotechnology will host an Investor & Media Conference Call and Q&A today, Wednesday, December 14, 2005, at 10.00 am (CET)
Dial: +41 91 610 56 00 (Europe)
+1 866 291 41 66 (U.S.)
+44 207 107 06 11 (U.K.)
Webcast – Live and replay on demand
The presentation will also be available on the Website either live or on replay later in the day. To access the webcast live, please visit the link on our homepage www.cytos.com
Approximately 2 hours after the Call has ended, an archived webcast will be available for replay on the website under "Investor Relations – Investor Overview".
Glossary
Adjuvant: a substance that non-specifically enhances the immune response.
Allergen: a normally harmless substance that elicits a misdirected immune response.
Allergic rhinitis: a condition due to allergy that mimics a chronic cold. Rhinitis means "irritation of the nose".
Anaphylaxis: is an acute and life-threatening reaction of the immune system to specific stimuli. If untreated, it can result in shock, respiratory and cardiac failure, and death.
Asthma: is a chronic inflammatory disorder of the airways leading to recurrent episodes of wheezing, breathlessness, chest tightness and cough in susceptible individuals.
Conjunctival hyperaemia: reddening of the eyes.
Desensitization: a certain form of immune therapy applied to treat allergy.
Disease-modifying: In contrast to symptomatic treatment, a disease-modifying treatment aims at addressing the cause of disease and to modify the disease progression.
Efficacy: strength, effectiveness; the ability of a drug to control or cure an illness.
Endpoint: an outcome measure in a clinical trial.
Hypersensitivity: an excessive reaction.
Intent to treat analysis: The broadest and most conservative method for analysis. Noncompliance, additional medication or other reasons not to complete the study do not lead to exclusion from the analysis.
Open-label: a set-up used in clinical trials where the doctor and the patient know what is administered, in contrast to e.g. double-blind placebo controlled studies, where neither the doctor nor the patient have this knowledge.
Phase IIa: a clinical trial that examines a new drug candidate's safety and preliminary efficacy in the targeted population and involves approximately 10-100 people.
Rhinoconjunctivitis: a combination of rhinitis (inflammation of the nose) and conjunctivitis (inflammation of the eye).
Single-arm: all patients in the study receive the same drug regimen (CYT005-AllQbG10 plus allergen in this study).
Subcutaneously: under the skin.
Th1 and Th2 type responses: describe a subset of T helper cell responses. T helper cells are a subset of T cells that secrete a variety of mediators (cytokines) playing a role in activation of other immune cells. A Th1 type immune response is usually induced by viral infection, or also by potent vaccination. A Th2 type immune response usually manifests an allergic reaction.
Therapeutic vaccine: a preparation of disease-related molecules (antigens) that is capable of inducing an immune response to such antigens with the goal to modulate the disease process.
Up-titration of allergen: the allergen is applied in raising concentrations up to the highest targeted allergen dose predefined in the protocol.
About Cytos Biotechnology AG
Cytos Biotechnology AG is a public Swiss biotechnology company that specializes in the discovery, development and commercialization of a new class of biopharmaceutical products – the ImmunodrugsTM. ImmunodrugsTM are intended for use in the treatment and prevention of common chronic diseases, which afflict millions of people worldwide. ImmunodrugsTM are designed to instruct the patient's immune system to produce desired therapeutic antibody or cytotoxic T-cell responses that modulate chronic disease processes. Taking advantage of the high flexibility of its ImmunodrugTM platform, Cytos Biotechnology has built a pipeline of 28 different ImmunodrugTM candidates in various disease areas, of which eight are currently in clinical development. The Immunodrug™ candidates are developed both in-house (25) and together with Novartis (1) and Pfizer Animal Health (2). Founded in 1995 as a spin-off from the Swiss Federal Institute of Technology (ETH) in Zurich, the company is located in Schlieren (Zurich). Currently, the company has 121 employees. Cytos Biotechnology AG has been listed on the SWX Swiss Exchange (SWX:CYTN) since October 2002.
For further information please contact:
Dr. Claudine Blaser
Director Corporate Communications
Phone: +41 44 733 47 20
Fax: +41 44 733 47 18
e-Mail: claudine.blaser@cytos.com
Website: www.cytos.com
This foregoing press release may contain forward-looking statements that include words or phrases such as "expect", "appear", "would", "believe", "aim", "could", "should", "has potential", "thought", "intend", "designed" or other similar expressions. These forward-looking statements are subject to a variety of significant uncertainties, including scientific, business, economic and financial factors, and therefore actual results may differ significantly from those presented. There can be no assurance that any other therapeutic entities will enter clinical trials, that clinical trial results will be predictive for future results, that therapeutic entities will be the subject of filings for regulatory approval, that any drug candidates will receive marketing approval from the U.S. Food and Drug Administration or equivalent regulatory authorities, or that drugs will be marketed successfully. Against the background of these uncertainties readers should not rely on forwardlooking statements. The company assumes no responsibility to update forward-looking statements or adapt them to future events or developments. This document does not constitute an offer or invitation to subscribe or purchase any securities of Cytos Biotechnology AG.
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