Presentation of Phase IIa Results for Cytos Biotechnology’s Hypertension Vaccine at the American Heart Association Scientific Sessions 2007
- Oral presentation by Prof. Juerg Nussberger, MD, today at 9.45
am (EST): “CYT006-AngQb, a vaccine against hypertension
targeting angiotensin II, reduces early-morning and day-time blood
- The American Heart Association publishes today an independent News Release about CYT006-AngQb.
- Excellent long-term safety and tolerability profile confirmed: no vaccinerelated adverse events reported in 12 months follow-up period.
SCHLIEREN (ZURICH), Switzerland and ORLANDO, Florida, USA, November 6, 2007 - Prof. Juerg
Nussberger, MD, University Hospital of the Canton of Vaud (CHUV), in Lausanne, Switzerland, presents today detailed results of a placebo-controlled, double-blind phase IIa clinical trial with CYT006-AngQb in 72 patients with mild to moderate hypertension. In addition, the American Heart Association publishes today at the time of presentation an independent News Release about the vaccine CYT006-AngQb. For more information on this report please visit www.scientificsessions.org.
The study was designed to evaluate safety, tolerability, and exploratory efficacy of two dose levels of the vaccine (100 ?g and 300 ?g). For efficacy evaluation, the change in blood pressure from baseline to post-treatment was assessed in individual subjects by 24-hour ambulatory blood pressure monitoring.
Both dose levels of CYT006-AngQb tested were safe and well tolerated. The majority of side effects observed were transient and mostly mild local injection site reactions. During the entire safety follow-up period from month 4 to 12 after the first injection, no vaccine-related adverse events were reported. This confirms the excellent safety and tolerability profile of the vaccine and underscores its potential for long-term disease management.
All patients who received the vaccine mounted a strong antibody response against angiotensin II, which was dose-dependent and long-lived but reversible with a half-life of about 4 months. Also efficacy was dose-dependent and a significant reduction of the mean ambulatory day-time blood pressure was observed in the group who received the 300 ?g dose of the vaccine. Systolic blood pressure (SBP) was reduced by 5.6 mmHg and diastolic blood pressure (DBP) by 2.8 mmHg from baseline.
Furthermore, strong efficacy of the vaccine was observed in the early morning hours, a critical time period when serious cardiovascular events occur frequently. The early morning rise of blood pressure starting at 5 am was significantly reduced by the vaccine, leading at 8 am to a blood pressure difference from baseline of (SBP / DBP) - 25 / - 13 mmHg compared to placebo.
Prof. Juerg Nussberger comments: “Despite the fact that effective drugs are available to treat hypertension, only about one out of four hypertensive patients has the blood pressure successfully controlled. Once people are aware of the often symptomless hypertension, they have to take their medications daily, and many are apparently unable or unwilling to take pills every day for the rest of their lives. The major remaining medical need in this important therapeutic area is thus improved patient compliance. If we could support or substitute the oral therapy with a vaccine that wouldneed to be given just every few months, I think we could achieve a better control of high blood
Prof. Nussberger adds: “A particularly interesting finding of this study is the excellent control of the blood pressure in the early morning hours achieved by the vaccine. This is a crucial time period when serious events like myocardial infarction and stroke are more likely to occur than during other times of the day. Since currently available drugs often have too short half-lives to affect the rise in early morning blood pressure, this could become a major advantage of the novel vaccine approach. I am looking forward to the next steps in clinical development for this promising vaccine candidate.”
CYT006-AngQb is a therapeutic vaccine in development for treatment of hypertension1. It is designed to instruct the patient’s immune system to produce an antibody response against angiotensin II. Angiotensin II is a small peptide in the body and part of the renin-angiotensin system (RAS), which is an important regulator of blood pressure. Angiotensin II causes blood vessels to narrow, resulting in increased blood pressure. Vaccination with CYT006-AngQb has been shown to reduce blood pressure by induction of antibodies that bind angiotensin II. Thereby, binding of angiotensin II to its receptors and subsequent narrowing of blood vessels should be decreased. The RAS has already been successfully targeted by three major classes of antihypertensive drugs on the market: inhibitors of the angiotensin-converting enzyme (ACEI), blockers of the angiotensin II subtype I receptor (ARB) and direct renin inhibitors (DRI). Like other antihypertensive drugs these also come with the need for daily dosing and often fail to provide a good solution for improving patient compliance. Treatment with CYT006-AngQb should allow for convenient dosing schedules and smooth control of blood pressure due to a sustained antibody response induced by vaccination.
Hypertension, also termed high blood pressure, is a medical condition where the blood pressure is chronically elevated. Although symptomless in nature and in itself rarely an acute problem, persistent hypertension is one of the most important preventable causes of premature death worldwide and contributes to around half of all cardiovascular diseases2. It is one of the major risk factors for stroke, myocardial infarction, heart failure, and vascular disease, and is a leading cause of chronic renal failure. Genetic predisposition and lifestyle habits such as inadequate physical activity, high fat diet, and high salt intake promote high blood pressure. Up to 30% of adults in most countries suffer from hypertension. Despite effective and relatively inexpensive treatment available, only about one out of four hypertensive individuals in the U.S. have their blood pressure controlled successfully3. This poor overall treatment success is mainly attributed to the symptomless nature of hypertension and the necessity for long-term treatment with medications that require at least once daily self-administration.
About early morning blood pressure
Blood pressure is not static but undergoes natural variations which follow a circadian pattern. Highest levels are reached during the morning, which then decline to reach a trough value at about midnight. In the early morning, a steep increase in blood pressure occurs naturally. It has been suggested that this morning rise in blood pressure triggers adverse cardiovascular events. A large study has revealed a marked circadian periodicity in the onset of myocardial infarction with the primary peak incidence being in the morning. At this time, myocardial infarction is three times as likely to onset as during the night4. The same periodicity was observed in the onset of stroke. Striking evidence suggests that the morning rise in blood pressure is crucial in determining the rupture of critically weakened arterial walls and subjects with a large rise in morning blood pressure have a significantly elevated risk of intracerebral haemorrhage5 and stroke6. Hypertension therapy therefore aims at a full 24-hour blood pressure control. Current small molecule inhibitors of the RAS were reported to achieve an ambulatory blood pressure reduction from baseline in the early morning hours of e.g. (SBP / DPB) - 8.7 / - 5.8 mmHg (valsartan) and - 11.0 / - 7.6 mmHg (telmisartan), respectively. They, however, do not abolish the rise in early morning blood pressure7,8.
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 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 different ImmunodrugTM candidates in various disease areas, of which 6 are currently in clinical development. The ImmunodrugTM candidates are developed both in-house and together with Novartis and Pfizer Animal Health. 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 130 employees. Cytos Biotechnology AG has been listed on the SWX Swiss Exchange (SWX:CYTN) since October 2002.
For further information please contact:
Claudine Blaser, PhD
Director Corporate Communications
Cytos Biotechnology AG, Wagistrasse 25, CH-8952 Schlieren, Switzerland
phone: +41 44 733 47 20, e-Mail: firstname.lastname@example.org, website: www.cytos.com
1. Journal of Hypertension, 2007, 25:63.
2. World Health Organization, Atlas of Heart Disease and Stroke, 2004.
3. Hypertension 2003; 42:1206.
4. New England Journal of Medicine, 1985, 313:1315.
5. Hypertension, 2006, 47:149.
6. Hypertension Research, 2006, 29:581.
7. American Journal of Hypertension, 2004, 17:347.
8. Hypertension, 2003, 42:1137.
This foregoing press release may contain forward-looking statements that include words or phrases such as “designed”, “potential”, “would”, “should”, “could”, “promising”, “suggest”, “aim”, “intend” 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 forward-looking statements. The company assumes no responsibility to update forwardlooking 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.
Posted: November 2007