Abstract
“Investment and interest in development will surge for these diseases with very low prevalence if there is an opportunity to access to the Accelerated Approval pathway,” said Emil Kakkis, M.D., Ph.D., president, EveryLife Foundation for Rare Diseases, adding: “We are thrilled the language to improve access to the FDA's Accelerated Approval pathway for rare diseases has been included in FDASIA.”
The foundation lauded House Energy and Commerce Committee Chairman Rep. Fred Upton (R-MI) and ranking member Rep. Henry Waxman (D-CA) for including the provision in the final version of the bill, which Dr. Kakkis said “will unlock lifesaving treatments that have been stalled early in the development process.”
Also recognized were Representatives Cliff Stearns (R-FL) and Ed Towns (D-NY) for introducing two predecessor bills with key components incorporated into FDASIA. One of those components accelerates approval for products that affect “a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit”—taking into account severity, rarity, or prevalence of conditions, and availability of alternative treatments.
On the basis of preclinical data, the companies anticipate that a single application of StarGen or UshStat to the retina could potentially provide either long-term or permanent therapeutic benefit for patients. There are currently no approved treatments available for Stargardt disease or Usher syndrome type 1B. Both products have received E.U. and U.S. Orphan Drug Designation.
Under a 2009 agreement with Sanofi, Oxford BioMedica will receive a total option exercise payment of $3 million, and is eligible for further development and commercialization milestone payments and royalties on any future sales of the products. Oxford BioMedica is conducting ongoing phase 1/2a trials for StarGen and UshStat, while working with Sanofi to plan the next stages of development and finalize terms of the worldwide license agreements.
“Sanofi's commitment to these innovative gene therapies bolsters the opportunity to save vision in people with diseases for which there are no treatments,” Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness, said in a statement.
Also known as Lorenzo's oil disease, ALD is estimated to affect 1 in every 21,000 boys worldwide.
bluebird bio's childhood cerebral ALD (CCALD) product program has the potential to halt the progression of the disease by providing a functional ABCD-1 gene to a patient's own stem cells, which then proliferate and ultimately become normal microglial cells incorporating the corrective ABCD-1 gene. Data from the first clinical study treating patients with X-linked CCALD with the company's lentiviral gene therapy product demonstrated continued stable expression of the transgene and the corresponding ABCD-1 protein for more than 4 years in two patients with CCALD, resulting in prolonged disease stabilization.
The agreement, announced in June, came 3 months after Chatham won a nonexclusive license from ReGenX to use NAV rAAV8 I vectors in its research and preclinical development of therapeutics that deliver DNA, RNA, or other sequences for hemophilia A. Rights granted to Chatham include use in methods for protein replacement, modulation of gene expression, and gene-editing approaches. In addition, Chatham had rights to exercise an option for an exclusive worldwide license, with rights to sublicense, ReGenX's NAV rAAV8 vectors for the treatment of hemophilia A in humans, subject to certain limitations.
Last December, ReGenX announced publication in The New England Journal of Medicine of data from groups at St. Jude Children's Research Hospital and University College London describing a combined phase 1/2 clinical trial that used NAV rAAV8 vectors to express a crucial, missing clotting factor in patients with hemophilia B. “Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B” described six patients with hemophilia B receiving a single intravenous injection of NAV rAAV8 vectors encoding a normal copy of the defective gene, factor IX. Four of the six patients were able to discontinue use of prophylactic, recombinant factor IX and have not experienced spontaneous bleeding since receiving the therapy. The other two patients have been able to extend the time between prophylactic treatments.
In a paper published in Science Translational Medicine, researchers from Weill Cornell Medical College, Cornell University and The Scripps Research Institute reported results from constructing an AAVrh.10 vector that expressed a full-length, high-affinity, anti-nicotine antibody derived from the Fab fragment of the anti-nicotine monoclonal antibody NIC9D9 (AAVantiNic). In mice treated with the vector, the antibody showed high specificity and affinity for nicotine, while shielding the brain from systemically administered nicotine, reducing brain nicotine concentrations to 15% of those in naive mice.
Nine of the 12 coauthors on the STM nicotine paper jointly published research results in Human Gene Therapy earlier this year (23:451–459 [May 2012]) showing that a single administration of an AAVrh.10 gene transfer vector in mice effectively developed a gene expressing the heavy and light chains of the high-affinity anti-cocaine monoclonal antibody in vivo, which sequestered cocaine in the blood, preventing access to cognate receptors in the brain. Despite repeated intravenous cocaine challenge, the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to cocaine, whereas naive mice exhibited hyperactivity.