February 1, 2012 (Vol. 32, No. 3)
- Amsterdam Molecular Therapeutics received orphan drug designation for its hemophilia B gene therapy program. The program consists of an adeno-associated viral (AAV) vector containing the human factor IX gene. Last month, AMT raised €2.5 million ($3.2 million) in new equity through a €0.34 ($0.43) per share private placement with three existing shareholders, Forbion Capital Partners, Gilde Healthcare Partners, and Advent Venture Partners. The new funds haven’t solved its potentially terminal financial problems. As of December 15, AMT was in a negative equity position, and mulling options that include selling all or part of the business, raising funds through backers and investors, securing nondilutive grants, or establishing new collaborations.
- Celladon was granted Fast Track designation by FDA for Mydicar® for treatment of advanced heart failure. Celladon’s Phase II CUPID trial met primary safety and efficacy endpoints at six months for high dose Mydicar versus placebo. Twelve months after receiving a single infusion of Mydicar, patients treated with the highest dose versus placebo had an 88% reduction of risk of major cardiovascular events such as death, need for left ventricular assist device or cardiac transplant, episodes of worsening heart failure, and number of heart failure-related hospitalizations. Heart failure symptoms, exercise tolerance, serum biomarkers and cardiac function essentially improved or remained the same while deteriorating substantially in patients with placebo and concurrent optimal drug and device therapy.
- Cystic Fibrosis Trust expects a formal decision from the board of the U.K.’s Efficacy and Mechanism Evaluation (EME) Programme to fund the Gene Therapy Consortium (GTC) to conduct a Phase IIb clinical trial into gene therapy for Cystic Fibrosis. From April 2011 through to the end of 2014, the Trust said, it will pay GTC nearly £5 million ($7.7 million) to cover their work, preparations for the trial, and manufacture of the drugs to be used. Discussions are continuing between the EME Programme and GTC, which consists of Imperial College London, and Edinburgh and Oxford Universities.
- A research team led by Amit C. Nathwani, Ph.D., of University College London successfully treated six hemophilia B patients through gene therapy. In results published in the The New England Journal of Medicine, the team recounted how it injected a single dose of an AAV vector expressing human factor IX into the patients, two of which were given high, intermediate, or low doses. In an accompanying editorial, Katherine P. Ponder, M.D., of Washington University in St. Louis said the results reflected “the first unequivocal evidence of successful gene therapy for hemophilia B—a major advance in this field. This success for hemophilia may translate into gene therapy for other blood protein deficiencies.”
- Two recent studies show how PCSK9 has emerged as a target to lower low-density lipoprotein cholesterol (LDL-C) levels. Alnylam Pharmaceuticals reported positive preliminary results from its ongoing clinical trial of ALN-PCS, an RNAi therapeutic targeting PCSK9 for severe hypercholesterolemia. ALN-PCS demonstrated statistically significant RNAi silencing of PCSK9 of up to 66%, and reductions of up to over 50%, in levels of “bad” or LDL-Cs. Alnylam’s Phase I study continues with planned dose escalation; additional results are expected in the first half of this year. Also, Regeneron and Sanofi reported preliminary Phase II trial results indicating that REGN727—a human PCSK9-specific monoclonal antibody co-developed by the companies—effectively and safely reduced LDL-C levels in patients with hypercholesterolaemia who were undergoing statin therapy.
Launching This Month: Human Gene Therapy Methods
The field of gene therapy is rapidly evolving and holds great promise for its applications in treating human diseases. Human Gene Therapy, the premier journal in the field, is launching Human Gene Therapy Methods to complement the flagship publication. HGT Methods answers the growing need for a central forum for nurturing, promoting, and advancing new technologies and methods that will ultimately pave the way for product development. The Editor in Chief is James M. Wilson, M.D., Ph.D.