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Hemab Therapeutics Presents New Preclinical Research Demonstrating Effects Of Its Bispecific Antibody HMB-001 In Factor VII Deficiency
Hemab Therapeutics Presents New Preclinical Research Demonstrating Effects of Its Bispecific Antibody HMB-001 in Factor VII DeficiencyPR Newswire
COPENHAGEN, Denmark and BOSTON, June 24, 2023
HMB-001 recognizes and binds to factor VII (FVII) protein variants associated with moderate/severe FVII deficiency and drives accumulation of endogenous FVII/FVIIa to normal ranges in in-vivo models
COPENHAGEN, Denmark and BOSTON, June 24, 2023 /PRNewswire/ -- Hemab Therapeutics, a clinical-stage biotechnology company developing the first prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, announced results today from preclinical research of HMB-001 in models of factor VII (FVII) deficiency at the International Society on Thrombosis and Haemostasis (ISTH) 2023 Congress in Montreal.
"We believe that HMB-001 has the potential to transform treatment in several serious bleeding disorders and have already initiated a Phase 1/2 study in Glanzmann Thrombasthenia," said Benny Sorensen, MD, PhD, CEO and President of Hemab. "The new preclinical data presented today show HMB-001 successfully targeted and accumulated endogenous FVIIa to levels that would be expected to provide clinical benefit in FVII deficiency, supporting the potential for HMB-001 in an additional underserved bleeding disorder."
FVII is a protein necessary in the formation of hemostatic plugs to control bleeding. FVII deficiency can cause spontaneous or excessive and prolonged bleeding after injury or surgery; heavy or prolonged menstrual bleeding in women; and in very severe cases, life-threatening bleeding inside the skull or digestive tract.
HMB-001, Hemab's lead candidate, is a bispecific antibody that binds to and stabilizes endogenous activated FVII (FVIIa) with one antibody arm and localizes FVIIa to the surface of activated platelets by binding to TLT-1 with the other arm. This allows for accumulation of FVIIa in the body and recruitment of FVIIa directly to the surface of activated platelets at the site of vascular injury where FVIIa is known to facilitate the formation of protective hemostatic plugs to stop bleeding.
The preclinical research presented at ISTH, "HMB-001, a Bispecific anti-FVIIa/anti-TLT-1 Antibody Demonstrates Effect in Models of FVII Deficiency," assessed key requirements for HMB-001 to function in FVII deficiency, specifically its ability to bind with FVII protein variants associated with moderate/severe deficiency and the potential of HMB-001 to accumulate FVIIa in an in-vivo non-human primate model of FVII deficiency.
A panel of 12 FVII variants from the European Association for Haemophilia and Allied Disorders (EAHAD) database was produced based on high prevalence and association with moderate/severe FVII deficiency phenotype as well as proximity to the HMB-001 binding site. In subsequent binding studies, HMB-001 was shown to bind to all FVII variants at clinically relevant concentrations.
The ability of HMB-001 to accumulate endogenous FVIIa in FVII deficiency was assessed using small interfering RNA (siRNA) to knock down FVII/FVIIa to levels between 10 to 30 percent of normal in animal models (n=3). After continuous, stable knock down, HMB-001 (5 mg/kg) was administered. The total accumulation of FVIIa observed with HMB-001 was comparable to the normal range seen in healthy animals. These initial results suggest HMB-001 may have potential application as a treatment for FVII deficiency.
About HMB-001
HMB-001 is bispecific antibody that binds and stabilizes endogenous factor VIIa (FVIIa) with one antibody arm and TLT-1 on activated platelets with the other arm. This allows for accumulation of FVIIa in the body, recruitment of FVIIa directly to the surface of the activated platelets where it is known to facilitate clotting, and avoidance of clotting activity in the absence of tissue damage. HMB-001 was designed to be a first-in-class prophylactic treatment for Glanzmann Thrombasthenia (GT) with potential for other debilitating rare bleeding disorders, including factor VII deficiency.
About Hemab Therapeutics
Hemab is a clinical-stage biotech company developing the first prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in the US and Denmark, Hemab is progressing a pipeline of monoclonal and bispecific antibody-based therapeutics to transform the treatment paradigm for patients with high unmet need. The company's strategic guidance, Hemab 1-2-5™, targets the development of 5 clinical assets by 2025 to deliver long-awaited innovation for patients with high unmet need blood clotting disorders like Glanzmann Thrombasthenia, factor VII deficiency, Bernard Soulier Syndrome, Von Willebrand Disease and other serious disorders. Learn more at hemab.Com.
Media Contact: Lia Dangelicoldangelico@vergescientific.Com 540-303-0180
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SOURCE Hemab Therapeutics
US Regulator Approves First Ever Gene Therapy For People With Hemophilia A
A life-changing treatment for people with hemophilia A, which was developed at UCL and licensed by UCLB to BioMarin Pharmaceuticals Inc., has been approved by the United States' Food and Drug Administration (FDA).
Roctavian (valoctocogene roxaparvovec) has become the first ever gene therapy for adults with severe hemophilia A to be approved by the FDA, meaning it can be sold as a treatment for patients with the disease. It follows a similar approval in August 2022 by the European Commission.
Hemophilia A is a rare genetic bleeding disorder, where a genetic mutation results in a deficiency of Factor VIII, a blood clotting protein normally produced by the body, which can mean bleeding is harder to control and is life-threatening in severe cases. Hemophilia A can seriously impact on quality of life because of the harm from bleeding, the need to manage the risk caused by physical activity, and the limitations of previous treatments.
Currently, hemophilia A requires ongoing treatment throughout patients' lives, with regular injections to replace the missing Factor VIII.
Roctavian is ground-breaking because it is a one-time, long-term treatment, using a gene therapy approach to treat the disease and enable people with hemophilia A to increase their levels of Factor VIII. The active Factor VIII gene is delivered by an engineered adeno-associated virus to deliver genetic material into cells. The gene is then expressed in the liver, which produces the Factor VIII protein, improving the ability of the body to control bleeding without regular injections.
The technology was developed by Professor Amit Nathwani (UCL Cancer Institute and Institute of Immunity & Transplantation) and his team at UCL and St. Jude Children's Research Hospital, U.S. It was licensed by UCLB, the commercialization company for UCL, to BioMarin Pharmaceuticals Inc. In 2013.
Professor Nathwani said, "It is humbling to be involved in the creation of the first gene therapy for patients with severe hemophilia A. Current treatment is effective but highly demanding requiring regular lifelong injections. Most severe hemophilia A patients suffer recurrent break-through bleeding into joints despite treatment that ultimately leads to disability and chronic pain. The approval of Roctavian, is an important and long-awaited advance that addresses the genetic cause of the condition. Roctavian is a one-time gene therapy that offers patients long term protection from bleeds and avoids the burden of regular infusions."
Biomarin's GENEr-8, the longest global Phase 3 study to date for any gene therapy in hemophilia, was key to achieving the approval of Roctavian by the FDA. It found that the therapy was effective in reducing the rate of bleeding in a cohort of 134 patients for at least three years.
Professor Geraint Rees, UCL Vice-Provost (Research, Innovation and Global Engagement) said, "Creating the first long-term treatment for severe hemophilia A will change lives, and proving its effectiveness and achieving FDA approval is a major achievement. It is a prime example of how our approach to industry-academic engagement is directly benefitting society."
UCL is a recognized leader in transformative gene therapies. The success of Roctavian follows a number of recent milestones for UCLB's gene therapy spinouts, including Freeline's first patient dosed with a novel gene therapy candidate for Gaucher Disease, and the use of spinout Orchard Therapeutic's Libmeldy by the NHS to treat children with metachromatic leukodystrophy, an otherwise fatal disorder.
Richard Fagan, Director of BioPharm at UCLB, said, "Our partnership with BioMarin has spanned over a decade. Since licensing the technology to BioMarin, the company has taken forward Roctavian's pioneering clinical development, and undertaken some of the most extensive clinical trials for a gene therapy in the world. The successful FDA approval is a significant achievement for UCL and UCLB and ultimately Hemophilia patients."
Provided by University College London
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FDA Approves BioMarin Pharma's Gene Therapy, The First For Hemophilia A
A one-time BioMarin Pharmaceutical treatment that fixes the problem at the root of hemophilia A has finally won FDA approval, making it the first gene therapy authorized for the inherited bleeding disorder.
The Thursday regulatory decision for the gene therapy, Roctavian, covers adults with severe hemophilia A. BioMarin set a $2.9 million wholesale price for the product. But the San Rafael, California-based drugmaker is also giving the hemophilia community and insurance companies assurances that the gene therapy will work. BioMarin is offering a warranty program that will pay back the therapy's price if a patient's disease does not respond to the treatment.
In hemophilia A, patients have an inherited deficiency of factor VIII, a clotting protein. This deficiency makes patients more susceptible to painful bleeding episodes that can happen spontaneously. Standard treatment includes regular infusions of engineered versions of the factor VIII protein that patients lack, which are intended to prevent these episodes. Another option is Hemlibra, a Roche antibody drug that mimics the function of the deficient clotting protein.
Roctavian consists of a functioning version of the gene that provides instructions for making factor VIII. Administered as an intravenous infusion, the gene therapy reaches a patient's cells aboard an engineered virus called adeno-associated virus serotype 5. FDA approval of Roctavian covers patients who don't have pre-existing antibodies to this virus that would render the therapy ineffective. Patients who meet this eligibility requirement are identified with a companion diagnostic that was also approved by the FDA on Thursday. By BioMarin's count, about 6,500 adults in the U.S. Have severe hemophilia A. Of those, the company estimates 2,500 are eligible for Roctavian under the current approval.
The Roctavian regulatory decision comes nearly three years after the FDA rejected the gene therapy, citing data discrepancies between Phase 1/2 testing and the pivotal Phase 3 study. The company continued to follow patients in the study to accrue more data. Approval of Roctavian is based on the results of a Phase 3 study that has more than three years of patient data. Of 134 patients who received the gene therapy, 112 had annualized bleeding rate data collected for six months prior to receiving Roctavian. During this period, they received factor VIII therapies. The remaining 22 patients had their baseline data collected retrospectively.
The trial results showed that following dosing with Roctavian, patients' annualized bleeding rate dropped to 2.6 episodes per year, a 52% decline from baseline. In addition, patients also reported a reduction in the rate of spontaneous bleeds and joint bleeds compared to baseline. The most common adverse reactions included nausea, fatigue, and headache. But laboratory testing also showed higher levels of liver enzymes, which can be a sign of toxic effects on the liver. This problem can be addressed with corticosteroids. The drug's label tells physicians to monitor a patient's liver enzymes weekly for at least 26 weeks after dosing, and to monitor and manage for the any adverse effects associated with corticosteroid treatment.
Earlier this week, during the annual meeting of the International Society on Thrombosis and Haemostasis, BioMarin presented three-year data showing that participants in the Phase 3 study had an 82.9% reduction in treated bleeds overall compared with baseline. The study also found the gene therapy led to a 96.8% reduction in factor VIII usage overall compared with baseline.
"Spontaneous bleeds and joint bleeds are medically important events that define severe hemophilia A as a bad condition, and the fact that those are dramatically affected by Roctavian is Roctavian's superpower," Hank Fuchs, BioMarin's president of worldwide research & development said, speaking during a conference call Thursday.
The European Commission granted Roctavian conditional marketing authorization last August, based on two-year clinical trial data. While Roctavian is the first gene therapy approved for hemophilia A, it is not the first hemophilia gene therapy. Last November, the FDA approved Hemgenix, a CSL Behring gene therapy for the rare hemophilia B. Hemgenix carries a $3.5 million price, but CSL Behring has pledged to offer value-based agreements to commercial payers. These agreements tie the reimbursement of a therapy to predetermined outcomes that show the treatment worked.
Under the warranty for Roctavian, BioMarin will reimburse up to 100% of the therapy's wholesale acquisition cost for those who don't respond to the therapy. BioMarin Chief Commercial Officer Jeff Ajer said this four-year warranty will be offered to all U.S. Insurers, both public and private. If a treated patient loses response to the therapy within the four-year period, Ajer said BioMarin will reimburse payers on a prorated basis. But he added that continued benefit beyond four years represents savings to the healthcare system.
Ajer said Roctavian will become commercially available in the U.S. In about two months. But prior to receiving the therapy, patients will need to go through several steps that include determining if their insurance will cover the therapy, taking the test to determine eligibility for the treatment, and testing to establish a baseline for liver enzyme levels. Patients should expect that the various steps will take anywhere from two to five months, Ajer said.
Public domain image by Flickr user SciTechTrend
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