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CSL Behring to Tackle Hemophilia B Using UniQure’s Gene Therapy Program
By Ruchi Jhonsa, Ph.D.
On June 24th, the Pennsylvania-based biopharma announced plans of acquiring exclusive global licensing rights of uniQure’s AMT-061 that is currently under late-stage development.
CSL Behring has years of experience in improving the life of hemophilia patients with the largest portfolio of treatments, including more than a dozen plasma-derived and recombinant coagulation factor concentrates. The company is now betting on uniQure’s gene therapy for the treatment of hemophilia B, which could potentially become the first treatment with long-term benefits with a single dosage.
Hemophilia B is a rare genetic blood disorder that affects 4000 males in the US and 26000 males worldwide. It is caused by the absence of blood clotting factor, Factor IX, which results in uncontrolled, spontaneous bleeding in different areas of the body. The current method of treatment includes intravenous administration of Factor IX, which can be time-consuming, and require multiple hospital visits. A near-permanent solution to this problem will be to replace the non-functional Factor IX gene with the functional one. For this, numerous companies are developing gene therapies, including Pfizer, Spark, Regeneron, and Intellia.
uniQure’s gene therapy has shown remarkable success in previous studies. Dubbed, AMT-061, the drug could increase the levels of Factor IX plasma levels in hemophilia patients to the degree that reduces or eliminates the bleeding tendency for many years. Currently, the drug is being tested in Phase III. If the drug were to be successful, it will bring down the need for frequent and ongoing replacement therapies for patients and will give a big push to CSL’s $1 billion a year hemophilia business.
“Our vision with hemophilia B patients is to offer transformational treatment paradigms that help free them from the lifelong burden of this disease,” said CSL’s CEO and Managing Director Paul Perreault. “With more than three decades of providing lifesaving innovations for the global bleeding disorders community, we are well-positioned to maximize the potential benefit of this therapy.”
The deal will grant uniQure a $450 million upfront payment for completing the Phase 3 trial and scaling up of the product for early commercial supply. Additionally, it will receive up to $1.6 billion for regulatory success and first commercial sales on top of tiered double-digit royalties.
UniQure’s Hemophilia Clinical Program
AMT-061 is an adenoviral vector-based gene therapy that contains the Padua variant of Factor IX, a missing protein in hemophilia patients. When injected in the body, adenovirus can attach to the cells and deliver a copy of the Factor IX gene, which can insert at a specific site in the genome. Phase 2b dose confirmation study of the drug showed that all three patients had a stable and sustained activity of Factor IX at the end of one year.
Interestingly, mean Factor IX activity in three patients reached 41% of normal, which is much higher than the levels considered sufficient to eliminate or significantly reduce the risk of bleeding events. Concurrent with this data, no patient exhibited bleeding events and remained free of any additional treatment after drug administration. Surprisingly, this therapy was found quite safe and well-tolerated with no occurrence of cytotoxic T cell-mediated immune response seen with almost all other AAV treatments.
Notable Gene Therapy Competitors
Pfizer and Spark’s SPK-9001
Currently, CSL faces stiff competition from Pfizer and Spark’s investigational gene therapy, SPK-9001 for hemophilia B, which the duo decided to jointly develop in 2014. The pair presented impressive data from 15 patients in 2018 that showed a reduction in the annual rate of bleeds from 8.9 to 0.2. All 15 participants achieved high activity of Factor IX, which led to discontinuation of routine administration of Factor IX concentrate.
Regeneron and Intellia’s CRISPR based Treatment
On June 1st, Regeneron and Intellia decided to jointly leverage their expertise in targeted gene therapy to develop a treatment for hemophilia A and B. In preclinical studies the companies demonstrated the first CRISPR/Cas9 mediated targeted transgene insertion in the liver of non-human primates, which generated normal or high circulating levels of human Factor IX. Although their efforts are still preclinical, it shows great potential as a hemophilia treatment.
UniQure’s Next Steps
uniQure is now conducting the Phase 3 HOPE-B trial of the drug for the treatment of patients with severe and moderately severe hemophilia B. In March this year, it finished the dosing of 54 patients in the trial and topline results from the study will be announced before the end of this year. Based on the data, the company is planning to support a BLA submission in 2021.
Editor: Rajaneesh K. Gopinath, Ph.D.
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