Boehringer Ingelheim invests in rare diseases with high unmet medical need. Volasertib* is in Phase III clinical development for acute myeloid leukaemia and nintedanib* is in Phase III clinical development for idiopathic pulmonary fibrosis
INGELHEIM, Germany I February 28, 2013 I With the enrollment of the first patient, Boehringer Ingelheim is pleased to announce on international Rare Disease Day, the initiation of a Phase III study (POLO-AML-2) investigating volasertib*, a selective and potent polo-like kinase (Plk) inhibitor, in combination with chemotherapy, in patients with acute myeloid leukaemia (AML) ineligible for intensive therapy.
Acute leukaemias are rare diseases, with AML being the most deadly acute leukaemia in adults.1 Today marks the sixth international Rare Disease Day, and more than 60 countries around the world will join to raise awareness for those affected by rare diseases. In Europe, rare disease is defined as a life-threatening or chronically debilitating disease which affects fewer than five people per 10, 000.2
Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim
Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim
"Rare diseases are often incorrectly diagnosed and even once they are correctly diagnosed, there is often a lack of viable treatment options" said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "The initiation of the POLO-AML-2 trial is a significant milestone as therapeutic options are limited in AML patients ineligible for intensive therapy."
AML is characterised by the rapid proliferation of abnormal blood precursor cells that accumulate in the bone marrow and interfere with the production of normal blood cells. The primary endpoint of POLO-AML-2 is objective response to the combination treatment compared to the chemotherapy alone. The main secondary endpoint of POLO-AML-2 is overall survival.
The study was initiated following positive results from a Phase II study which demonstrated higher rates of objective response and an improvement in event free survival in patients receiving volasertib* in combination with chemotherapy versus chemotherapy alone.3
"Boehringer Ingelheim is committed to developing innovative medications that improve patients’ lives and has put considerable effort into research and development of treatments for orphan† diseases." said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim.
In addition to AML, Boehringer Ingelheim is investigating therapeutic approaches for other rare diseases including idiopathic pulmonary fibrosis (IPF). IPF is a severely debilitating and fatal respiratory disease. It is characterised by progressive loss of lung function ultimately leading to the death of half of the patient population two to three years after diagnosis.
Nintedanib*, a small molecule tyrosine kinase inhibitor (TKI), targets growth factor receptors which have been shown to be potentially involved in the pathomechanism of pulmonary fibrosis. The pivotal INPULSISTM-1 and INPULSISTM-2 Phase III trials have completed recruitment and are ongoing in study centres worldwide to assess the clinical outcomes in IPF patients treated with nintedanib*. The Phase III INPULSIS trials aim to build upon the promising results of the Phase II TOMORROW trial, which demonstrated a positive trend in reducing lung function decline in IPF patients treated with 150 mg of nintedanib* twice daily when compared to placebo.4 Additionally, nintedanib* has received orphan-drug designation from the U.S. Food and Drug Administration in June 2011 and by the Ministry of Health, Labour and Welfare of Japan in September 2011.
For more information about Rare Disease Day, please visit www.rarediseaseday.org
Notes to Editors
About the POLO-AML-2 Study
For additional information on the trial, please visit http://clinicaltrials.gov./ct2/show/NCT01721876?term=Volasertib&rank=4
About volasertib*
Volasertib*, an inhibitor of Plk, is currently being evaluated in clinical trials for AML and is one of several late-stage compounds that Boehringer Ingelheim is currently evaluating in clinical trials for cancer.
Of the company’s ongoing research in cell cycle inhibition, the volasertib* clinical development programme is the furthest advanced. Boehringer Ingelheim is one of the first companies to advance Plk inhibitors into clinical development.
Volasertib* is designed to inhibit the activity of Plk. Plk1 – the
best characterised of the five known human Plks – is an enzyme that regulates cell division (mitosis). This inhibition results in cell cycle arrest and ultimately cell death (apoptosis).5
About Acute Myeloid Leukemia (AML)
While AML is one of the most common types of leukaemia in adults, accounting for approximately one third of all adult leukaemias in the Western world, it is a rare cancer of the bone marrow and the blood.6,7 The yearly incidence of AML in European adults is 5-8 cases per 100,000 people, with yearly mortality figures of 4-6 cases per 100,000.8 AML has one of the lowest survival rates of all leukaemias.1
AML is primarily a disease of later adulthood; the average age of newly diagnosed patients is 65 years.1 In AML patients the prognosis worsens with increasing age, with a median survival of six months or less following diagnosis in older patients ineligible for intensive remission induction therapy.9 Older AML patients are often considered ineligible for intensive remission induction therapy (the most common treatment approach for younger patients) as it involves high doses of chemotherapy which many of them are unable to tolerate.9
About Idiopathic Pulmonary Fibrosis (IPF)
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are only limited treatment options available to date.10 IPF is characterised by progressive scarring of lung tissue and loss of lung function over time.11 Development of scarred tissue is called fibrosis.11 Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream, and vital organs do not get enough oxygen.11 As a result, individuals with IPF experience shortness of breath, cough and often have difficulty participating in everyday physical activities.12
About nintedanib*
Nintedanib* is an investigational small molecule tyrosine kinase inhibitor (TKI) in Phase III development by Boehringer Ingelheim for IPF.4 It targets growth factor receptors, which have been shown to be potentially involved in pathomechanisms of pulmonary fibrosis, most importantly the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR).4,13,14 By blocking these signaling pathways that are involved in fibrotic processes, it is believed that nintedanib* has the potential to reduce disease progression, slowing the decline of lung function.13 Nintedanib* is also in clinical development as a treatment option for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.13,15
About Boehringer Ingelheim in Oncology
The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition. Nintedanib* is currently in Phase III clinical development in non-small cell lung cancer (NSCLC) and ovarian cancer. In the area of signal transduction inhibition, afatinib** is currently in Phase III clinical development in NSCLC, breast cancer and head and neck cancer.
Boehringer Ingelheim’s oncology pipeline is evolving and demonstrates the company’s continued commitment to advance the disease area.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act with social responsibility. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.
In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.
For more information please visit:
www.thewhiteroom.info and www.newshome.com
*Volasertib and nintedanib are investigational compounds and are not yet approved. Their safety and efficacy have not yet been fully established.
†An orphan disease is usually a rare disease or condition with limited treatment options.
**Afatinib is an investigational compound and is not yet approved. Its safety and efficacy have not yet been fully established.
References
1 Deschler B, et al. Acute Myeloid Leukemia: Epidemiology and Etiology. Cancer. 2006. 2009-2107
2 European Commission. Available at: http://ec.europa.eu/health/ph_information/documents/ev20040705_rd05_en.pdf. [Last accessed: February 2013]
3 Döhner H, Phase I/II study of volasertib (BI 6727), an intravenous Polo-like kinase (Plk) inhibitor, in patients with acute myeloid leukemia (AML): results from the randomized phase II part for volasertib in combination with low-dose cytarabine (LDAC) versus LDAC monotherapy in patients with previously untreated AML ineligible for intensive treatment. Oral Presentation at ASH Annual Meeting and Exposition 2012
4 Richeldi L, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079-87
5 Schöffski P. Polo-Like Kinase (PLK) Inhibitors in Preclinical and Early Clinical Development in Oncology. Oncologist. 2009;14(6):559-570
6 Jemal A, et al. Cancer Statistics, 2009; CA Cancer J Clin 2009;59:225-249
7 American Society of Hematology. http://www.hematology.org/patients/Blood-Disorders/Blood-Cancers/5229.aspx [Last accessed: February 2013]
8 Fey MF, et al. Acute myeloblastic leukaemias and myelodysplastic syndromes in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, 2010
9 Juliusson G, et al. Age and acute myeloid leukemia real world date on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009. Apr 30;113(18):4179-87
10 Raghu G, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788-824
11 Pulmonary Fibrosis Foundation. What is IPF? 2011. Available at: http://www.pulmonaryfibrosis.org/ipf. [Last accessed February 2013]
12 Pulmonary Fibrosis Foundation. Symptoms. 2011. Available at: http://www.pulmonaryfibrosis.org/Symptoms. [Last accessed February 2013]
13 Selman M, King TE, Pardo A, et al. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 2001;134(2):136-51
14 Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 2008; 68(12):4774-4782
15 U.S. National Institutes of Health. Clinicaltrials.gov BIBF 1120. Available at: http://clinicaltrials.gov/ct2/results?term=BIBF+1120. [Last accessed February 2013]
SOURCE: Boehringer Ingelheim
