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Wed05222013

Last update 09:59:07 PM EST

Cystic Fibrosis

Pharmaxis' Cystic Fibrosis Drug is not Recommended for Approval by the FDA Advisory Committee

Yesterday a Food and Drug Administration (FDA) advisory committee met to review a cystic fibrosis drug and provide the FDA with a recommendation of whether or not to approve the drug. After review, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 14-0 against approval of Pharmaxis’ New Drug Application (NDA) for Bronchitol (mannitol) to improve pulmonary function in cystic fibrosis patients six years and older.

Additionally, the committee voted 11-3 in two separate votes stating that Pharmaxis had not provided sufficient evidence of efficacy and safety for the drug. Although the first study met its primary efficacy endpoint, the committee raised concerns regarding missing data. The committee was also concerned that the second study did not show significant effect on FEV1.

Committee members were especially concerned with the lack of evidence that the drug had significant effects in children. Some members noted that they would support approval of the drug in adult patients who were at least 18 years old.

Both studies had a high amount of treatment-related early discontinuations, raising safety concerns. The increased risk of hemoptysis in children was a major point. Some committee members thought that a smaller dose of the medication may be more beneficial.

“The Committee vote is disappointing, however, we are aware that these recommendations are not binding on the FDA and we will continue the process of working with the FDA to bring Bronchitol to patients in the US. It is important to remember that we are in a process and that opportunities remain to discuss the issues that were raised by the Committee before the FDA makes its final decision on 18 March 2013,” Alan Robertson, CEO of Pharmaxis stated.

Bronchitol is currently approved for marketing for patients six years and older in Australia and for patients 18 years and older throughout the European Union.

Separately than the decision by the panel, NovaQuest Pharma Opportunities Fund III LP has agreed to invest up to $40 million to support development of Bronchitol in the EU and the US. Under the terms of the agreement, Pharmaxis will receive $20 million initially; however NovaQuest is eligible for undisclosed payments that will be based on potential product sales.

“Pharmaxis explored a range of options to leverage its Bronchitol asset. The NovaQuest investment was selected because it is tailored to the expected growth of the business, it offers flexibility in the total investment amount, the investment returns to NovaQuest are based solely on the sales of Bronchitol, Pharmaxis retains the vast majority of expected sales revenue over the term of the agreement, and the strategic and operational control of the Bronchitol business remains with the Company,” Robertson said in a statement.

Source: Pharmaxis Ltd

Last Updated: 1/31/13; 12:15PM EST

Orlando to Host World's Largest Cystic Fibrosis Medical Meeting

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Conference Follows FDA Approval of Historic Drug to Treat Underlying Cause of CF – A Fatal Disease

BETHESDA, Md., Oct. 9, 2012 - In the largest meeting of its kind, nearly 4,000 doctors, scientists and clinicians from diverse disciplines will meet in Orlando, Fla., Oct. 11 – 13, 2012, to present the latest advancements in cystic fibrosis research, care and drug development.

Highlighted topics of the 26th annual North American Cystic Fibrosis Conference include:

Accelerating discovery of potential new therapies that target the basic genetic defect in CF.
Updates on the diagnosis and management of pulmonary disease.
Overcoming barriers to CF medication adherence.
Partnering with patients and families to improve CF care.

Sponsored by the Cystic Fibrosis Foundation, the meeting takes place at a time of tremendous advances in CF research and care. In January, the U.S. Food and Drug Administration approved Kalydeco™, the first drug to treat the underlying cause of CF in a small group of people with the disease. This milestone opens the door to research that may eventually lead to similar treatments for all who have CF.

Cystic fibrosis is a fatal genetic disease that causes life-threatening lung infections and premature death. Fifty years ago, most children with CF died before reaching Kindergarten. Today, due to Cystic Fibrosis Foundation-supported drug research and care, people with CF are living into their 30s, 40s and beyond.

WHAT:

The 26th Annual North American Cystic Fibrosis Conference, the largest international gathering of cystic fibrosis research scientists and clinicians.

WHEN & WHERE:

Thursday, Oct. 11 – Saturday, Oct. 13, 2012, at the Orange County Convention Center.

About the Cystic Fibrosis Foundation
The Cystic Fibrosis Foundation is the world's leader in the search for a cure for cystic fibrosis. The Foundation funds more cystic fibrosis research than any other organization, and nearly every CF drug available today was made possible because of Foundation support. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. The Cystic Fibrosis Foundation is a donor-supported nonprofit organization. For more information, go to www.cff.org.

SOURCE Cystic Fibrosis Foundation

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OrPro Therapeutics Receives NIH Grant Award to Advance Development of Recombinant Thioredoxin for Treatment of Cystic Fibrosis

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SAN DIEGO, July 31, 2012 - OrPro Therapeutics, Inc. today announced that the company has been awarded a National Heart, Lung and Blood Institute Small Business Innovation Research (SBIR) grant from the National Institutes of Health (NIH). The grant enables OrPro to advance development of its lead product, ORP-100, for the treatment of cystic fibrosis (CF), an inherited genetic disease that affects approximately 80,000 people worldwide.

"This award focuses on an inhaled formulation of ORP-100 for topical delivery to the lung surface, a key milestone in our preclinical development program," said Peter B. Heifetz, Ph.D., OrPro president and chief technology officer. "NIH grants are highly competitive, and our proposal received excellent reviews and scores acknowledging OrPro's strong team and innovative approach to CF therapy."

ORP-100 is a recombinant engineered variant of thioredoxin, a human lung protein that has demonstrated in laboratory studies a potent ability to increase the fluidity of mucus. Clearance of the thickened mucus that is characteristic of CF remains a central and poorly met treatment objective. ORP-100 will be administered through an advanced aerosol delivery system, and in contrast to DNA-degrading mucolytics, targets the adhesive protein gel network that is common to all patients with obstructive mucus.

"We are excited about the potential for ORP-100 to be a next-generation mucus-thinning (mucolytic) drug that will offer a convenient, safe and effective treatment alternative to the people who suffer from CF," said Jeff Raser, chief operating officer. "New therapeutic strategies to correct underlying CF defects have promise, but there still remains a critical need for superior mucolytic therapies in CF and other obstructive pulmonary diseases such as bronchiectasis."

The mucolytic properties of thioredoxin were discovered at leading respiratory hospital National Jewish Health (NJH) in Denver, CO by pediatric pulmonologist Dr. Carl White, M.D. In 2011, OrPro licensed from NJH an intellectual property portfolio claiming compositions and uses of the thioredoxin active site for the treatment of pulmonary disease. Dr. White (now at University of Colorado Denver/Children's Hospital Colorado), and his NJH colleague Dr. David Nichols are medical advisors to the company, and will collaborate on the NIH-funded project.

"We have assembled a world-class team of experts in research, preclinical/clinical development, biologics manufacturing, and finance to help guide OrPro in the development of this exciting new product candidate," said Heifetz, who is also principal investigator on the SBIR grant. "We believe the support from NIH will act as a catalyst for the company and we look forward to completing an initial round of financing to accelerate our development efforts."

About OrPro

OrPro Therapeutics, Inc. is a pre-clinical stage biopharmaceutical company headquartered in San Diego, CA.The company's goal is to develop a breakthrough class of safe, well-tolerated and more effective inhaled non-systemic drugs based on the thioredoxin active site for the treatment of patients with cystic fibrosis (CF), COPD/emphysema, bronchiectasis, severe asthma, and other serious obstructive pulmonary diseases. These diseases are characterized by thickened mucus resulting in impaired lung function. Poor clearance of abnormal, sticky mucus is associated with chronic infection and premature death, especially in CF. Despite advances in antibiotic therapy and other treatments there remains a large unmet medical need for improved mucus-reducing (mucolytic) drugs which in many cases are the most efficacious means of mitigating disease symptoms. Effective new treatments for CF are forecast to achieve peak annual sales in excess of $1 billionannually. OrPro's lead product, ORP-100, an aerosolized variant of recombinant human thioredoxin, will target abnormal viscosity due to excess protein gels in CF and has the potential for broader clinical efficacy than existing mucolytic approaches.

About National Jewish Health

National Jewish Health is known worldwide for treatment of patients with respiratory, cardiac, immune and related disorders, and for groundbreaking medical research. Founded in 1899 as a nonprofit hospital, National Jewish Health remains the only facility in the world dedicated exclusively to these disorders. Since 1998, U.S. News & World Report has ranked National Jewish the #1 respiratory hospital in the nation.

PR Newswire (http://s.tt/1jwxL)

Grifols Initiates Safety Study Following Orphan Drug Designation for their CF Drug

RESEARCH TRIANGLE PARK, N.C., July 17, 2012 /PRNewswire/ -- Grifols, a global healthcare company based in Barcelona, Spain, today announced plans to initiate a safety trial of a novel, inhaled formulation of alpha1-proteinase inhibitor [Human] later this year. In April, the U.S. Food and Drug Administration (FDA) granted orphan drug designation for Grifols' inhaled alpha1 formulation as a treatment for cystic fibrosis, an inherited disease that can cause life-threatening lung infections. Orphan drug designation is granted to encourage the development of treatments that prevent, diagnose or treat rare diseases that affect fewer than 200,000 people per year in the U.S.

"Grifols is committed to developing new therapies that address the debilitating symptoms of chronic lung disease," said Kim Hanna, vice president of clinical research development at Grifols. "The orphan drug designation represents another milestone in the growth of our alpha1 program, and we're excited to pursue clinical trials with an aerosol formulation of this important therapy."

Grifols currently leads the market in alpha1-proteinase inhibitors with its intravenous therapy PROLASTIN®-C (Alpha1-Proteinase Inhibitor [Human])(A1-PI), indicated for the treatment of alpha1-antitrypsin (AAT) deficiency. This rare, genetic disorder can result in the development of emphysema due to low circulating levels of the alpha1 protein in the lungs.

PROLASTIN®, the predecessor to PROLASTIN-C, was the first FDA-approved product to treat AAT deficiency and remained so for nearly 17 years. Grifols is developing its next-generation alpha1-proteinase inhibitor as an inhaled formulation.

About Orphan Drug Designation

Orphan drug designation is granted to companies to encourage the development of treatments that prevent, diagnose or treat rare conditions that affect fewer than 200,000 people per year in the U.S. The designation provides incentives such as tax credits and potentially seven years of market exclusivity to companies willing to support the costly research and development programs associated with developing specialized drugs for a small population of individuals. The goal is to provide patients who have rare diseases with access to the same quality of treatment as other patients.

About Grifols

Grifols is a global healthcare company that produces plasma-derived therapies and manufactures hospital pharmacy products, intravenous solutions, diagnostic tools and medical devices. As the third largest global producer of plasma therapies, Grifols has a presence in more than 90 countries and is the world leader in plasma collection, with 150 plasma donation centers across the U.S. The centers collect protein-rich plasma, which is then tested and manufactured into life-saving medicines used to treat rare conditions such as bleeding disorders, immune deficiencies and genetic emphysema. The company's class A shares have been listed on the Spanish Stock Exchange (MCE:GRF) since 2006 and have been part of the Ibex-35 since 2008. In 2011, the company listed non-voting class B shares on the Mercado Continuo (MCE:GRF.P) and on the U.S. NASDAQ via ADRs (NASDAQ: GRFS).

Important Safety Information
PROLASTIN-C, Alpha1-Proteinase Inhibitor (Human) is indicated for chronic augmentation and maintenance therapy in adults with emphysema due to deficiency of alpha1-proteinase inhibitor (alpha1-antitrypsin deficiency). The effect of augmentation therapy with any alpha1-proteinase inhibitor (alpha1-PI) on pulmonary exacerbations and on the progression of emphysema in alpha1-antitrypsin deficiency has not been demonstrated in randomized, controlled clinical trials. PROLASTIN-C is not indicated as therapy for lung disease in patients in whom severe alpha1-PI deficiency has not been established.

PROLASTIN-C may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. PROLASTIN-C is contraindicated in patients with antibodies against IgA.

The most common drug related adverse reactions during clinical trials in >1% of subjects were chills, malaise, headache, rash, hot flush, and pruritus. The most serious adverse reaction observed during clinical studies with PROLASTIN-C was an abdominal and extremity rash in one subject.

PROLASTIN-C is made from human plasma. Products made from human plasma may carry a risk of transmitting infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Please see accompanying PROLASTIN-C full Prescribing Information for complete prescribing details.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.