Monitoring International Trends
posted August 2015
The NBA monitors international developments that may influence the management of blood and blood products in Australia. Our focus is on:
- Potential new product developments and applications;
- Global regulatory and blood practice trends;
- Events that may have an impact on global supply, demand and pricing, such as changes in company structure, capacity, organisation and ownership; and
- Other emerging risks that could potentially put financial or other pressures on the Australian sector.
A selection of recent matters of interest appears below. Highlightsinclude:
Baxalta published data suggesting that BAX 855 has the potential to provide strong bleed prevention in haemophilia A patients with twice weekly dosing. (Section 1)
Baxalta reported that 100 per cent of the von Willebrand patients treated with BAX 111 achieved success in the management of bleeding episodes. (Section 1)
CSL is recruiting patients for a Phase IIB study of its drug CSL112 for acute coronary syndrome. (Section 1)
Researchers say they are nearing approval by the FDA for a small device that allows trauma medics to monitor rate of blood loss more precisely. (Section 1)
The US Food and Drug Administration (FDA) accepted for review CSL Behring's Biologics License Application for its recombinant factor VIII single-chain drug, CSL 627, designed for molecular stability in treating haemophilia A. (Section 2)
Swissmedic accepted for review a Marketing Authorization Application for CSL Behring’s long-acting fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP) for the prophylaxis and treatment of bleeding episodes in haemophilia B. This rIX-FP allows dosing intervals up to 14 days. (Section 2)
ADMA Biologics has submitted its Biologics License Application to the FDA seeking marketing authorization for RI-002. This is a plasma-derived, polyclonal, intravenous immune globulin derived from human plasma. (Section 2)
The FDA granted Fresenius Kabi approval for a labelling change that permits blood centres to use the Fenwal Amicus system for the storage of Amicus-derived platelets in plasma for up to seven days. (Section 2)
Remedium Technologies has FDA 510(k) clearance to market its Hemogrip patch. The patch controls bleeding occurring from access to veins or arteries during surgery. (Section 2)
Swedish Orphan Biovitrum (Sobi) decided to exercise its opt-in right to take over final development and commercialisation of Alprolix (long acting recombinant factor IX for haemophilia B) for Europe, North Africa, Russia and some Middle Eastern markets.Biogen has led development for Alprolix, has manufacturing rights, and has commercialisation rights in North America and other regions in the world excluding the Sobi territory. (Section 3)
Cerus Corporation announced that Unyts, headquartered in Buffalo, had signed a three-year purchase agreement for the INTERCEPT Blood System for platelets and plasma. `
Baxalta reported revenues for the second quarter and first half of 2015, which exceeded expectations. (Section 3)
Baxalta has a contract fractionation agreement with Sanquin Blood Supply Foundation to enhance supply and support growth in global demand for plasma-based therapies. Sanquin has submitted the production line for approval in Europe, which will provide additional manufacturing flexibility. (Section 3)
On 4 August, Shire went public with a $US 30 billion bid for Baxalta that had already been made privately and been rejected. Baxalta said later that day that Shire's
$US 45.23-per-share bid "significantly undervalues" the young company. (Section 3)
CSL announced that it had secured the necessary approvals required to proceed with the acquisition of the influenza vaccines business of Novartis. (Section 3)
Pfizer offered concessions in seeking EU regulatory approval for its $US 15 billion takeover of rival Hospira. (Section 3)
Therapure Biopharma received $C 20 million contribution from the Canadian government. Therapure has developed a proprietary technology called PlasmaCap Expanded Bed Adsorption, which it says increases protein yields from plasma, separates them faster, and costs less. (Section 4)
A biosafety level 4 laboratory in Tokyo is Japan’s first facility able to handle Ebola. (Section 4)
A Transylvanian electronic music festival offered its potential audience free or discounted tickets in exchange for blood donations to the National Institute of Blood Transfusion. (Section 4)
A Californian study showed that haemophilia accounted for the largest share of the State’s expenditure on outpatient drugs for publicly insured children with serious chronic illnesses. (Section 4)
A study found that patients who received an allogeneic blood transfusion during lumbar spine surgery were at higher risk for surgical site infection, urinary tract infection and overall postoperative infections. (Section 5)
Researchers found that theclinical benefits of minimally invasive aortic valve replacement via lower hemi-sternotomy include decreased transfusion requirements, decreased ventilation times, and shorter ICU and hospital stays. (Section 5)
A report suggested patients who experienced simultaneous bilateral anterior approach total hip arthroplasty enjoyed low rates of perioperative complications and excellent clinical outcomes. (Section 5)
Researchers found that iron bio-fortified pearl millet resolved iron deficiency in a group of school-aged children in India within four to six months (Section 5)
A randomized study confirmed that CSL Behring’s Kcentra (4-factor prothrombin complex concentrate) reversed the anticoagulation effects of vitamin K antagonists (VKA) at a faster rate than plasma in patients requiring emergency invasive procedures. (Section 5)
Scientists funded by Australia’s National Heart Foundation have been working towards a revolutionary treatment for blood clots that could be administered by paramedics without the need for specialised equipment. (Section 5)
St. Teresa Medical enrolled the first patient in its UK clinical trial of its Surgiclot wound dressing to reduce blood loss.(Section 5)
BioLife Solutionsannounced that manufacturing process validation has begun to support a new product, directed towards cryopreservation, including freezing of platelets for subsequent clinical use.(Section 5)
The adoption of new reporting standards may have reduced the proportion of studies reporting positive research findings among large-budget clinical trials funded by the US National Heart, Lung and Blood Institute. (Section 6)
At Stanford University’s School of Medicine, infusions of blood plasma from young people are being given to patients with mild to moderate Alzheimer’s disease. Doctors are looking for cognitive improvements. (Section 6)
Researchers have developed a system that mimics the human circulatory system. They coupled it with an optical technique that can provide quantitative in vivo information on individual red blood cells. (Section 6)
A group of downhill skiers have been trying to verify whether endurance performance can be improved by living at high altitudes while training at lower levels, (Section 6)
Scientists at the University of Pennsylvania have been investigating a new approach to vaccines, creating immunity without vaccination. (Section 7)
European drug regulators recommended GlaxoSmithKline's Mosquirix (malaria vaccine) as safe and effective to use in at risk babies in Africa. (Section 7)
The United Nations Food and Agriculture Organization (FAO) warned in late July that timely intervention was essential to prevent the highly virulent avian flu virus H5N1(which had already spread to five West African countries in six months) from spreading further. (Section 7)
A study found that two doses of H7N9 avian flu vaccine produced an adequate immune response in 2 per cent of adults vaccinated, but two distinct adjuvants increased that to 57 per cent and 84 per cent respectively. (Section 7)
Scientists found significantly fewer serious cardio-respiratory events possibly related to influenza in study participants 65 years of age and older who received a higher-dose split-virus inactivated influenza vaccine compared with a standard-dose split-virus inactivated influenza vaccine. (Section 7)
On 27 July, the final South Koreans suspected of possibly being infected with MERS were released from self or mandatory quarantine.(Section 7)
The Kingdom of Saudi Arabia continues to notify the World Health Organisation (WHO) of MERS cases. A surge in numbers has been observed ahead of the Hajj pilgrimage.
Scientists in Switzerland have found an antibody that neutralises multiple strains of Mers-CoV. They found in mice that the antibody could be used both prophylactically and therapeutically. (Section 7)
After a delay awaiting approval, plasma donated by Ebola survivors was administered to Ebola patients in West Africa. (Section 7)
The US Department of Health and Human Services (HHS) has issued a two-year
$US 19.7 million task order to Emergent BioSolutions’ Baltimore Bayview Center for Innovation in Advanced Development and Manufacturing (CIADM) to produce a novel therapeutic drug to treat Ebola virus disease. (Section 7)
The FDA awarded OraSure Technologies' rapid Ebola test special status, allowing marketing of the test for use in areas where the virus is still circulating while the company works toward final approval. (Section 7)
A vaccine against Ebola was reported to be 100 per cent successful in trials in Guinea. The vaccine is made by Merck.(Section 7)
Research has found that urine from black flying foxes poses biggest Hendra virus risk to horses, following a confirmed Hendra case in far north Queensland. (Section 7)
Contents
1.Products
Clotting factors
Other
2.Regulatory
Plasma and recombinant products
Other
3.Market structure and company news
4.Country-specific events
5.Safety and patient blood management
Appropriate transfusion
Treating iron deficiency
Other.
6.Research
7.Infectious diseases
Mosquito-borne diseases: dengue, malaria and West Nile virus
Influenza: strains, spread, prevention and treatment
Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Ebola Virus Disease
Hendra virus
1.Products
Here the NBA follows the progress in research and clinical trials that may within a reasonable timeframe make new products available, or may lead to new uses or changes in use for existing products.
Clotting factors
a)Pivotal data for Baxalta’s BAX 855 was published in the journal Blood. The company says the drug has the potential to provide strong bleed prevention in haemophilia A patients with twice weekly dosing. The drug is based on Advate and when approved by the FDA will be marketed in the US as Adynovate. The trial showed a mean half-life extension of 1.4 to 1.5fold compared with Advate. Baxalta expects to file for marketing authorization with the European Medicines Agency in 2016. A regulatory application was filed in Japan earlier this year.
b)Baxalta announced the publication[1] of pivotal phase III data for BAX 111, a highly purified recombinant von Willebrand factor (rVWF) candidate. The data showed that 100 per cent of the patients treated with BAX 111 achieved success in the management of bleeding episodes[2].BAX 111 is currently under review by the US Food and Drug Administration (FDA). If approved, BAX 111 would become the first recombinant replacement treatment for managing bleeding episodes for von Willebrand patients. BAX 111 was developed using a plasma- and albumin-free manufacturing method.Both the FDA and the European Medicines Agency granted orphan drug designation in November 2010, which is reserved for products that meet medical needs for a disease that is classified as rare.
Other
a)CSL is recruiting 1200 patients for a Phase IIB study of its drug CSL112 for acute coronary syndrome, designed to prevent a second heart attack after a patient has already suffered the first.
b)A study conducted at the Royal Free Hospital in Kuala Lumpur suggested that patients with gastrointestinal symptoms related to systemic sclerosis may benefit from treatment with intravenous immunoglobulin[3]
c)Researchers from Pohang University of Science and Technology reported “a new light-activated, mussel protein-based bioadhesive (LAMBA) inspired by mussel adhesion and insect dityrosine crosslinking chemistry. LAMBA exhibited substantially stronger bulk wet tissue adhesion than commercially available fibrin glue and good biocompatibility in both invitro and invivo studies”[4]. The researchers praised the potential of their product assurgical glue for sutureless wound closures, both internal and external.
d)Israeli startup LifeBond has developed a firm but elastic hydrogel matrix using a combination of gelatin and microbial transglutaminase (mTG) enzyme. Investors have now made $US 27 million available to fund a US trial of this LifeSeal Surgical Sealant in minimizing postoperative complications such as staple-line leakage in gastro-intestinal and bariatric surgeries. The product has previously undergone a multinational, randomized controlled pilot in Europe and is expected to be granted a CE mark.
e)Vic Convertino (senior scientist for the US Army Combat Casualty Care Research program at Joint Base San Antonio in Texas) and his fellow researchers say they are nearing approval by the FDA for a small device[5] that allows trauma medics to monitor precisely the rate at which a bleeding patient will reach “decompensation,” the point when the body can no longer offset blood loss, shock sets in and death soon follows. Such a device could be of use on the battlefield, where a blood pressure monitor may not indicate much change even when a soldier is losing a significant amount of blood.
2.Regulatory
The NBA monitors overseas regulatory decisions on products, processes or procedures which are or may be of relevance to its responsibilities.
Plasma and recombinant products
a)Baxalta announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency expressed a positive opinion for the marketing authorization of Obizur [Antihaemophilic Factor (Recombinant), Porcine Sequence]. Baxalta requested authorization for the treatment of bleeding episodes in adult patients with acquired haemophilia[6] caused by antibodies to Factor VIII (FVIII).The European Commission has yet to announce its decision on the recommendation[7]. John Orloff, head of Research & Development and chief scientific officer, Baxalta, said: “The marketing authorization anticipated later this year for Obizur will be an important milestone, offering patients with acquired haemophilia A in Europe a treatment option that transforms their care by allowing physicians to monitor treatment response”. The CHMP positive opinion follows a global, prospective, controlled, multi-centre Phase II/III open-label clinical trial testing the efficacy of Obizur in treating serious bleeding episodes in adults with acquired haemophilia A. All 28 patients treated with Obizur had their bleeding stopped or decreased. Adverse reactions were development of inhibitors to porcine FVIII. Obizur is already approved in the US and is being reviewed by regulators in Australia, Canada, Switzerland, and Colombia.
b)The FDA accepted for review CSL Behring's Biologics License Application (BLA) for its recombinant factor VIII single-chain (rVIIISingleChain or CSL 627), designed for molecular stability in treating haemophilia A. The product met all primary endpoints in the pivotal trial. The BLA relies on the AFFINITY clinical development program, including a phase I/III open-label, multi-centre trial examining safety and efficacy. Pharmacokinetics were compared with a current standard of care, recombinant human anti-haemophilic factor VIII (octocog alfa). CSL627 has a strong affinity for von Willebrand factor, leading to greater stability and integrity of FVIII in circulation.
c)Swissmedic accepted for review a Marketing Authorization Application for CSL Behring’s long-acting fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP) for the prophylaxis and treatment of bleeding episodes in haemophilia B. This rIX-FP allows dosing intervals up to 14 days.
d)Baxalta announced in the US that the Centers for Medicare and Medicaid Services (CMS) have expanded coverage to include in-home use of Hyqvia [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase], a treatment for adults with primary immunodeficiency (PI). After the FDA approved Hyqvia in 2014, CMS covered both provider facility and in-office treatment with Hyqvia. This new decision expands its provisions to include durable medical equipment coverage of the infusion pump required to administer Hyqvia, facilitating the self-administration (at home) option for patients. In the clinical trial for Hyqvia, the majority of PI patients expressed a desire for the ability to administer infusions at home.
e)ADMA Biologics has submitted its Biologics License Application to the FDA seeking marketing authorization for RI-002. This is a plasma-derived, polyclonal, intravenous immune globulin derived from human plasma containing naturally occurring polyclonal antibodies (Streptococcus pneumoniae, H. influenza type B, cytomegalovirus (CMV), measles, tetanus, etc.) as well as standardized, high levels of antibodies to respiratory syncytial virus (RSV)[8]. In a Phase III study in patients with primary immunodeficiency, RI-002 met its primary endpoint of no serious bacterial infections (SBI). The requirement specified by FDA guidance is ≤ 1 SBI per patient-year.
Other
a)FDA officials have met with Google to “begin a discussion on how we might collaborate with Google on identifying adverse event data, using Google’s technologies and data.”[9]
b)The FDA granted Fresenius Kabi approval for a labelling change that permits blood centres to use the Fenwal Amicus system for the storage of Amicus-derived platelets in plasma for up to seven days. Where blood centres do store apheresis-derived platelets for seven days they must label each product with a statement that the product must be tested with a bacterial detection device cleared by FDA and labelled as a “safety measure”. Fresenius Kabi is the sole distributor of the Verax Platelet PGD test, a rapid test approved by the FDA as a “safety measure” for leukoreduced apheresis platelets within 24 hours prior to transfusion.
c)Hospira received approval from the FDA to launch bivalirudin for injection, a generic version of The Medicines Company's Angiomax. Bivalirudin is a direct thrombin inhibitor indicated amongst other things for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty.
d)The FDA, the US Department of Homeland Security’s Industrial Control Systems Cyber Emergency Response Team, and Hospira announced that Hospira’s Symbiq Infusion System could be accessed remotely through a hospital’s network. An unauthorized user could control the device and change the dosage the pump delivers. While neither the FDA nor Hospira are aware of any unauthorized access of a Symbiq Infusion System in a US health care setting, the FDA urged health care facilities to discontinue use of these pumps.