Roche?s investigational treatment for asthma met its primary endpoint in a phase II study

Lebrikizumab has potential to be the first personalized treatment for asthma

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that a phase II study of its investigational treatment lebrikizumab, a humanized monoclonal antibody designed to block interleukin-13 (IL-13) cytokine, met its primary endpoint. In the study, lebrikizumab treatment resulted in a statistically significant increase in FEV1 (measure of lung function) in adults with asthma whose symptoms were inadequately controlled with inhaled corticosteriods (ICS). The overall frequency of adverse events was similar in both the placebo and the treatment group. The results of this study, known as ?MILLY?, are being published in the new England Journal of Medicine (NEJM) today.

IL-13 is a key contributor to the features of asthma and increases periostin, a protein which can be measured with a blood test. In the study, patients with high pre-treatment periostin levels had greater improvement in lung function with lebrikizumab compared to patients with low periostin levels.

?The findings of the MILLY study, and the development of a potential biomarker, have shown that we may be able to select appropriate asthma patients for lebrikizumab therapy,? said Richard Scheller, Executive Vice President, Genentech Research and Early Development (gRED). ?These results support further investigation of lebrikizumab as a personalized medicine for patients who suffer from moderate to severe uncontrolled asthma.?

The study also showed a trend towards a lower rate of severe asthma attacks (known as exacerbations) in patients treated with lebrikizumab, although the study was not powered to detect a reduction of these. these data are encouraging as severe asthma attacks, characterized by shortness of breath and chest tightness, are potentially life threatening.

Lebrikizumab may benefit patients with a high unmet medical need who have uncontrolled asthma with existing treatment options.

About lebrikizumab

Lebrikizumab, which was developed by Genentech Research and Early Development, is a treatment being investigated for patients with uncontrolled asthma. It is a humanized monoclonal antibody designed to block the IL-13 cytokine (proteins that serve as messengers between cells) and reduce inflammation in the lung. IL-13 overexpression results in airway inflammation which is a feature of asthma.

About the Phase II study (MILLY)

The MILLY trial (a global phase II randoMized, double blInd, placebo-controLled study to evaLuate the safetY, tolerability and efficacy of lebrikizumab in adult patients with asthma who are inadequately controlled on inhaled corticosteroids) is a Roche/Genentech sponsored study to evaluate the safety profile, tolerability and efficacy of lebrikizumab in adult patients whose asthma is inadequately controlled on inhaled corticosteroids, a common treatment for asthma. Lebrikizumab was dosed every 28 days subcutaneously at 250mg, for a total of six doses. a total of 219 patients were randomized, one patient was not treated. 106 patients were randomized to lebrikizumab and 112 patients were randomized to placebo.

The primary endpoint of the study was a measure of lung function called the ?pre-bronchodilator Forced Expiratory Volume 1 (FEV1)?. FEV1 is the volume of air that can be forced out in one second after taking a deep breath.

The primary endpoint of the trial showed that at week 12, lebrikizumab-treated patients had a 5.5% (95% CI, 0.8% to 10.2%; P=0.02) greater increase in pre-bronchodilator FEV1, from baseline than placebo-treated patients (lebrikizumab, 9.8%?1.9%; placebo, 4.3%?1.5%). Lebrikizumab-treated patients in the high-periostin subgroup experienced an 8.2% (P=0.03) relative increase from baseline FEV1, compared with placebo. Lebrikizumab treated patients in the low-periostin subgroup experienced a 1.6% (P=0.61) relative increase in FEV1, compared with placebo. Periostin was measured in serum using a protein assay.

Secondary pre-specified outcomes included the rates of protocol-defined exacerbations and severe exacerbations (worsening of asthma) through week 24. although the study was not powered to detect a reduction of exacerbations, there was a trend towards a lower rate of severe exacerbation in patients treated with lebrikizumab.

The overall frequency of adverse events was similar in both the placebo and the treatment groups. Serious adverse events (SAEs) were observed in 4 lebrikizumab treated patients; 2 events of patients experiencing an asthma attack, community acquired pneumonia and traumatic pneumothorax (a collection of air inside the chest, between the lung and inner chest wall, which causes the lung to collapse) related to a car accident.

The most common side effects were infections (lebrikizumab 48.1%, placebo 49.1%), which included upper respiratory infections (lebrikizumab 12.3%, placebo 14.3%) and sinus infections (lebrikizumab 9.4%, placebo 8.0%). The overall frequency of adverse events was similar in both treatment groups (lebrikizumab, 74.5%; placebo, 78.6%), as were the frequencies of serious adverse events (lebrikizumab, 3.8%; placebo, 5.4%). Musculoskeletal events were more common with lebrikizumab (lebrikizumab, 13.2%; placebo, 5.4%). Twenty-five patients (11.5%) discontinued the study early, including 12 placebo and 13 lebrikizumab-treated patients.

About asthma

Asthma is a chronic disease of the airways that makes breathing difficult and is a major public health problem affecting millions of people worldwide.1 a feature of asthma is inflammation of the air passages resulting in a variable airflow to the lungs. This results in recurrent attacks of coughing, wheezing, shortness of breath, and chest tightness thus requiring continuous medical care. Therapies such as inhaled corticosteroids are intended to ease airway inflammation and airway narrowing. Despite treatment with inhaled glucocorticosteroids (ICS), many patients continue to have uncontrolled asthma that requires the use of more intensive therapy. 2

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world?s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche?s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2010, Roche had over 80,000 employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. for more information: roche.com.

CSL Behring announced today it has been granted national marketing authorization in Israel to market Berinert® for the treatment of acute hereditary angioedema (HAE) attacks in any body location. with this most recent approval, Berinert is now licensed in 30 countries, including Europe, Japan, North America, South America and Australia.

CSL Behring completed a European Mutual Recognition Procedure (MRP) for Berinert for the treatment of acute attacks of HAE, a rare and serious genetic disorder, in 23 European countries in December 2008. It was subsequently granted all respective national licenses. in October 2009, the United States Food and Drug Administration approved Berinert for the treatment of acute abdominal or facial attacks of HAE in adolescent and adult patients in the United States. National marketing authorizations were also granted for Berinert in Australia in January 2010 and Canada in June 2010. CSL Behring has marketed its C1-esterase inhibitor concentrate in Germany for more than 30 years. CSL Behring also markets it in Argentina, Japan and Switzerland.

The approvals for Berinert are mainly based on the results of the phase II/III prospective, double-blind placebo-controlled International Multi-center Prospective Angioedema C1-Inhibitor Trial (I.M.P.A.C.T.1), the largest single placebo-controlled HAE trial ever, that studied the efficacy of a C1-esterase inhibitor (C1-INH) concentrate.

“The approval of Berinert in Israel is a very important step toward optimal treatment of patients with HAE, many of whom have suffered with the symptoms of this debilitating disease for years,” said Dr. Avner Reshef, Head of the Allergy & Immunology Unit of Sheba Medical Center, Israel. “Because it is rare, and symptoms can appear similar to other medical conditions, HAE is often misdiagnosed. Swellings are wrongly treated as allergic reactions and abdominal pain can often lead to unnecessary surgery.”

“For years, most HAE patients in Israel had to rely on therapy with drugs that are associated with severe side-effects or which were not effective enough in treating symptoms. other patients had no therapy at all and were forced to endure often very painful or disfiguring attacks,” explained Tali Levy, head of the national patient association EDEMA. “However, a patient’s biggest fear is usually the prospect of having an attack of the larynx or throat, which can be life-threatening. Only the assurance that an effective treatment such as Berinert is immediately available can remove this fear and allow such people to live a normal life.”

About Hereditary Angioedema

HAE is a rare genetic disorder caused by a deficiency of C1-INH. It is inherited in an autosomal dominant manner. Symptoms of HAE include episodes of edema, or swelling, in the hands, feet, the face, the abdomen, and/or the larynx. Patients who have abdominal attacks of HAE can experience episodes of extreme pain, diarrhea, nausea, and vomiting caused by swelling of the intestinal wall. HAE attacks that involve the face or throat can result in airway closure, asphyxiation, and, if untreated, death. Diagnosis of HAE requires a blood test to confirm low or abnormal levels of C1-INH. For further information about HAE, please visit the website of the International HAE Patient Organization: HAEI.org, the website of the national patient organization in Israel: edema.co.il and the disease information website allabouthae.com.

About I.M.P.A.C.T.

I.M.P.A.C.T. 1 was a randomized controlled trial of 124 HAE patients with acute, moderate, or severe abdominal or facial attacks. C1-INH concentrate was administered at two different dose levels and compared to placebo. The main study endpoints were: time to onset of symptom relief from HAE attacks, proportion of subjects with worsening clinical HAE symptoms, and safety.  

The I.M.P.A.C.T. 1 study found that C1-esterase inhibitor concentrate (C1-INH) is effective and safe in rapidly treating acute abdominal and facial skin swellings in patients with HAE.  The study found that the median time to symptom relief was 30 minutes after receiving C1-INH compared to 1.5 hours with a placebo.

I.M.P.A.C.T. 2 was an open-label extension study conducted in North-America. The results showed the efficacy and safety of multiple open-label treatments with C1-INH concentrate for HAE attacks at any body location. A total of 1,085 attacks in 57 patients were successfully treated with C1-INH, including 48 laryngeal attacks in 16 patients. The median time to onset of symptom relief was 22 minutes and the median time to complete resolution of all HAE symptoms was 14.3 hours (per-attack analysis). Across all types of attack, median times to onset of relief ranged from 15 minutes (laryngeal attacks) to 30 minutes (peripheral attacks) and median times to complete resolution ranged from 8.4 hours (laryngeal attacks) to 28.3 hours (facial attacks).  A single dose of 20 U/kg plasma-derived C1-INH was sufficient to effectively treat 99 percent of all HAE attacks in this study.

About Berinert ®

Berinert® is a highly purified, human, plasma-derived C1-esterase inhibitor concentrate. As intravenous therapy, it rapidly treats the fundamental cause of hereditary angioedema (HAE) symptoms by providing C1-INH deficient patients with the missing human protein. Berinert is a unique HAE therapy because of its reliable record of proven efficacy and safety in over 30 years of international clinical use in more than 500,000 treatments. in Israel, Berinert is distributed exclusively by Mediline ltd. (mediline.co.il).

About CSL Behring

CSL Behring is a global leader in the plasma protein biotherapeutics industry. Passionate about improving the quality of patients’ lives, CSL Behring manufactures and markets a range of safe and effective plasma-derived and recombinant products and related services. The company’s therapies are used in the treatment of immune deficiency disorders, hereditary angioedema, hemophilia, von Willebrand disease, other bleeding disorders and inherited emphysema. other products are used for the prevention of hemolytic diseases in the newborn, in cardiac surgery, organ transplantation and in the treatment of burns. The company also operates one of the world’s largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited, a biopharmaceutical company with headquarters in Melbourne, Australia. For more information, visit cslbehring.com.

Roche Holding, AG, a major pharmaceutical company, has released results of an eight-week phase II clinical trial for a schizophrenia drug it has tentatively named RG1678. According to a report by the Wall Street Journal online, volunteers who took the drug plus a second-generation FDA-approved antipsychotic experienced a significant reduction in the negative symptoms of schizophrenia. Negative symptoms include lack of interest, lack of motivation and social isolation to the point that work is not possible. no currently approved drugs treat the negative behavioral symptoms of schizophrenia.

The researcher administered several different drug dosages during the trial and found that the 10 mg and 30 mg doses were more effective than the 60 mg doses. According to the article, the drug has a good safety profile and is generally well-tolerated.

A stage III clinical trial is currently underway. if RG1678 performs well in this trial, which involves a larger number of volunteers being tested for a longer period of time, it could be approved and available for use in 2013 or 2014. Meanwhile, schizophrenia drugs that treat the positive symptoms are available, lessening the effects of delusions and hallucinations in symptomatic patients. Monitor this website and other news outlets for future results regarding RG1678.

Read more: online.wsj.com/article/BT-CO-20101206-703306.html