Amsterdam Molecular Therapeutics (AMT; Amsterdam, The Netherlands) received an orphan drug designation to its gene therapy program for hemophilia B from the FDA. 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 (43 cents) 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. AMT said on December 15 that it was in a negative equity position, and was 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 (La Jolla, CA) was granted Fast Track designation by the FDA for its investigational product candidate Mydicar for the treatment of advanced heart failure. Celladon's phase 2 CUPID Trial met primary safety and efficacy endpoints at 6 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 (Bromley, Kent, UK) said publicly it expects a formal decision from the board of the UK's Efficacy and Mechanism Evaluation (EME) Programme to fund the Gene Therapy Consortium (GTC) to conduct a phase 2b 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, MBChB, PhD, 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 whom were given a high dose, two an intermediate dose, and two a low dose. In an accompanying editorial, Katherine P. Ponder, MD, 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 LDL-C levels. Alnylam Pharmaceuticals (Cambridge, MA) 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 low-density lipoprotein cholesterol (LDL-C). Alnylam's phase I study continues with planned dose escalation; additional results are expected in the first half of this year. Also, Regeneron (Tarrytown, NY) and Sanofi (Paris, France) reported preliminary phase II trial results indicating that REGN727—a human PCSK9-specific monoclonal antibody codeveloped by the companies—effectively and safely reduced LDL-C levels in patients with hypercholesterolemia who were undergoing statin therapy.
