Advances and Challenges in Hemophilia Management

Bayer Schering Pharma Media Event “Lighting the Torch”

Athens, – Hemophilia remains a condition associated with a great human and socio-economic burden. It is a disorder that requires lifelong therapy as well as education and support. The introduction of new management strategies over the last decades has improved significantly the life expectancy and quality of life of people living with hemophilia. In turn, this progress generates new challenges, such as the age-related chronic conditions that are also diagnosed in the general population as they age. Over 400 international experts met to review advances in the hemophilia treatment area during the Bayer Schering Pharma Hematology Conference 2010 and the Media Event “Lighting the Torch” in Athens, Greece.

“For over 20 years Bayer Schering Pharma has been committed to developing innovative hemophilia A therapies, such as the Factor VIII product Kogenate® Bayer. We also aim to expand scientific knowledge and clinical skills that may improve the lives of patients living with hemophilia”, said Dr Georg Lemm, Head of Clinical Development for the Hematology product line of Bayer Schering Pharma. To continue to advance the management of patients with hemophilia, Bayer Schering Pharma has initiated an extensive research and development program with three goals: to build on the proven efficacy and safety of marketed recombinant FVIII-FS with a full-length FVIII successor product (BAY 81-8973), to optimize prophylaxis therapy with long-acting products while preserving efficacy to treat acute bleeds or breakthrough bleeds, and to optimize bypass therapy for people with hemophilia who develop inhibitors.

In the current focus of Bayer’s research and development activities are a rFVIIa compound (BAY 86--6150), and a site-directed PEGylated BDD-rFVIII (BAY 94-9027).

A phase I human study with the modified FVIIa product, BAY 86-6150, for effective treatment of bleeds in hemophilia patients with inhibitors was completed successfully. The goal of the study was to demonstrate increased thrombin burst generation and reduced clearance. A pivotal phase II/III study is in preparation now and may start in the next months. If the clinical program is successful, it would enable effective therapy for patients with inhibitors to FVIII or FIX.

In animal studies, BAY94-9027 showed extended half-life and efficacy in hemophilic mice and dogs. A “proof of concept” phase I study for BAY 94-9027 in humans is projected to start in the fourth quarter of 2010.

Change in Hemophilia Management

Due to continuing improvements in hemophilia care over the last decades, the goal of treatment has changed. Historically, the clinical management of hemophilia was dominated by the risks of acute bleeding, chronic arthropathy and transfusion-transmitted infections, said Professor Erik Berntorp, Lund University, Sweden. Improvements in care of hemophilia were made possible through the availability of safe and effective factor concentrates and the adoption of prophylaxis. In this context, the life expectancy estimates for patients with severe hemophilia not infected with HIV in the period 1977 – 2001 ranged from 63 years in the UK to 70 years in the Netherlands and 73 years in Canada. Others estimate that the life expectancy of people with hemophilia will eventually be similar to that of the general population.

This development may generate other concerns, because the risk of developing chronic diseases increases as we age, and it is likely that many patients with hemophilia will develop these same chronic illnesses, and will need medications and surgical interventions that may have complex interactions with their bleeding disorder. This is particularly relevant for cardiovascular diseases, including ischemic heart disease, hypertension and renal disease, which are leading causes of morbidity and mortality in older individuals. Therefore, “it is important that proper screening and preventive medical interventions are introduced into the comprehensive care of patients with hemophilia”, commented Dr Gerry Dolan, Nottingham University Hospital, UK.

Improvement of Quality of Life

Besides a longer life expectancy, improvement in quality of life with prophylactic treatment is a main goal of therapy. “Prophylaxis means the regular infusion of clotting factor concentrate in order to prevent bleeding”, said Professor Manuel O. Carcao, from The Hospital for Sick Children, Toronto, Canada. Prophylactic management has been shown to greatly improve musculoskeletal outcome (less joint bleeding, less life threatening bleeds) and quality of life in pediatric patients with severe hemophilia, leading to improved participation in daily life activities including sports and better social interactions.

The use of prophylactic treatment is widespread in Europe, although practice varies between countries. “However, despite the many benefits of prophylaxis, most of the severe hemophilia patients in the world, especially in developing countries, do not receive this regimen”, Carcao pointed out. “How to make prophylaxis more widely available for the vast majority of hemophilia patients in the world remains a key goal for the 21st century”. Referring to the original Marathon run in ancient Greece, the conference chairman Professor Erik Berntorp, Lund University, Sweden, added: “Prophylaxis is a Marathon, not a sprint.”

A satisfying sexual life is also a component of a good quality of life. In people with hemophilia, “sexual dysfunction may be exacerbated by the special medical issues and psychological problems associated with the bleeding disorder”, said Professor Natan Bar-Chama, Mount Sinai School of Medicine, New York, USA. Potential sexual problems include a loss of sexual desire, ejaculatory difficulties, and erectile dysfunction (ED). Physicians treating men with hemophilia should be familiar with these problems and proactively address the topic with their patients. The use of phosphodiesterase-5-inhibitors as first-line treatment for ED could be considered. If sexual difficulties persist with treatment, referral to sexual specialists is indicated.

“In younger men with hemophilia, iliopsoas muscle bleeding may result from vigorous movements during intercourse or too vigorous muscular tension during masturbation”, stated Dr Woet Gianotten, Utrecht, The Netherlands.

Practical Challenges in Hemophilia Management

“There are many other challenges in hemophilia care. Modern treatments for children include regular prophylaxis and immune tolerance induction therapy. Both regimens are based on frequent infusions, thus, an adequate venous access is essential”, said Professor Elena Santagostino, University of Milan, Italy. In this context, the arteriovenous fistula has shown to be easy to use in the home setting and well accepted by children. Possible complications are postoperative hematoma and transient symptoms of distal ischemia. To manage therapy in the home setting, appropriate education of family members is necessary.

Another challenge is the understanding of the factors that contribute to the development of inhibitors in hemophilia A patients. “Inhibitor pathogenesis is complex and involves numerous product and patient-related factors”, said Professor Tom Howard, David Geffen School of Medicine, Los Angeles, USA. There is evidence to support the potential effect of nonsynonymous (ns)-single nucleotide polymorphisms (SNPs) on the development of this adverse alloimmune treatment outcome. SNPs mean slight differences in the human FVIII gene which code for single amino acid substitutions. They do not cause hemophilia A but create structurally distinct wild-type FVIII proteins. This information is necessary for the development and validation of predictive strategies to establish personalized approaches for FVIII replacement, immune tolerance induction and ultimately curative gene-based therapies.

About Bayer Schering Pharma
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals divisions. The pharmaceuticals business operates under the name Bayer Schering Pharma. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Find more information at www.bayerhealthcare.com.

Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company. Its research and business activities are focused on the following areas: Diagnostic Imaging, Hematology/Cardiology, Oncology, Primary Care, Specialized Therapeutics and Women’s Healthcare. With innovative products, Bayer Schering Pharma aims for leading positions in specialized markets worldwide. Using new ideas, Bayer Schering Pharma aims to make a contribution to medical progress and strives to improve the quality of life. Find more information at www.bayerscheringpharma.de.