1/28/2015 6:30:15 AM
A way to eradicate cancer stem cells, using the side-effects of commonly used antibiotics, has been discovered by a University of Manchester researcher following a conversation with his young daughter.
Professor Michael P. Lisanti, Director of the Breakthrough Breast Cancer Unit, led the research. He was inspired to look at the effects of antibiotics on the mitochondria of cancer stem cells by a conversation with his daughter Camilla about his work at the University’s Institute of Cancer Sciences. Camilla is currently a student at the Moor Allerton Preparatory School.
His new paper, published in Oncotarget, opens up the possibility of a treatment for cancer, which is highly effective and repurposes drugs which have been safely used for decades.
Mitochondria are the ‘engine’ parts of the cells and are the source of energy for the stem cells as they mutate and divide to cause tumours. Cancer stem cells are strongly associated with the growth and recurrence of all cancers and are especially difficult to eradicate with normal treatment, which also leads to tumours developing resistance to other types of therapy.
Professor Lisanti said: “I was having a conversation with Camilla about how to cure cancer and she asked why don’t we just use antibiotics like we do for other illnesses. I knew that antibiotics can affect mitochondria and I’ve been doing a lot of work recently on how important they are to the growth of tumours, but this conversation helped me to make a direct link.”
Professor Lisanti worked with colleagues from The Albert Einstein College of Medicine, New York and the Kimmel Cancer Centre, Philadelphia. The team used five types of antibiotics – including one used to treat acne (doxycycline) – on cell lines of eight different types of tumour and found that four of them eradicated the cancer stem cells in every test. This included glioblastoma, the most aggressive of brain tumours, as well as lung, prostate, ovarian, breast, pancreatic and skin cancer.
Mitochondria are believed to be descended from bacteria which joined with cells early on in the evolution of life. This is why some of the antibiotics which are used to destroy bacteria also affect mitochondria, though not to an extent which is dangerous to people. When they are present in stem cells, mitochondria provide energy for growth and, crucially, for division, and it is this process going wrong which leads to cancer.
In the lab, the antibiotics had no harmful effect on normal cells, and since they are already approved for use in humans, trials of new treatments should be simpler than with new drugs – saving time and money.
Professor Lisanti said: “This research makes a strong case for opening new trials in humans for using antibiotics to fight cancer. Many of the drugs we used were extremely effective, there was little or no damage to normal cells and these antibiotics have been in use for decades and are already approved by the FDA for use in humans. However, of course, further studies are needed to validate their efficacy, especially in combination with more conventional therapies.”
Dr Matthew Lam, Senior Research Officer at Breakthrough Breast Cancer, said: “The conclusions that the researchers have drawn, whilst just hypotheses at this stage, are certainly interesting. Antibiotics are cheap and readily available and if in time the link between their use and the eradication of cancer stem cells can be proved, this work may be the first step towards a new avenue for cancer treatment.
“This is a perfect example of why it is so important to continue to invest in scientific research. Sometimes there are answers to some of the biggest questions right in front of us but without ongoing commitment to the search for these answers, we’d never find them.”
Importantly, previous clinical trials with antibiotics - intended to treat cancer-associated infections, but not cancer cells - have already shown positive therapeutic effects in cancer patients. These trials were performed on advanced or treatment-resistant patients.
In the lung cancer patients, azithromycin, the antibiotic used, increased one-year patient survival from 45% to 75%. Even lymphoma patients who were ‘bacteria-free’ benefited from a three-week course of doxycycline therapy, and showed complete remission of the disease. These results suggest that the antibiotic’s therapeutic effects were actually infection-independent.
“As these drugs are considerably cheaper than current therapies, they can improve treatment in the developing world where the number of deaths from cancer is predicted to increase significantly over the next ten years,” said Dr Federica Sotgia, another leader of the study.
The research was published in the journal Oncotarget and part-funded by Breakthrough Breast Cancer.
January 1, 2015 at 9:06 am
This is a horrible article, you need to Lear more about fuel cells and hydrogen production. There are two ways to produce hyrdogen, the first being electrolysis. Electrolysis would require a $200k setup to generate and compress enough hydrogen to fill two cars a day. It uses a high voltage and current to split water into hydrogen and oxygen. This is not something you are doing at home because everyone would need a $200k machine and 480v 3-phase electric service upgrades. This means we need more gas stations equipped with electrolysis setups at a tremendous cost to the gas stations. This will not be cheap or easy to create the infrastructure. Additionally, electrolysis wastes 50% of the energy as heat, then the fuel cells themselves are only 50% efficient. So your car only gets a total of 25% of the energy used to create the hydrogen.
The other process to create hydrogen is high temperature steam reformation using fossil fuels. This process is even more expensive, creates a lot of pollution, and is not very pure. There will be carbon monoxide mixed in with the hydrogen. Carbon monoxide poisons the platinum catalysts used in fuel cells and quickly and irreversibly damages the $10k fuel cell in a car.
On the other hand you can charge a battery with 95% efficiency from a $500 or less outlet installed in any home (mine cost $30 because my electric panel is already in the garage). No more stopping at gas stations, no more worrying about gas price fluctuations, and your car only uses $.02 of electricity per mile versus the roughly $.08 that gasoline costs.
Until we come up with new ways of producing hydrogen, fuell cells will always be 10 years away like we were told back in the 70′s.
Tesla’s (TSLA) Fuel Cell Threat
You guessed it. Narrative from Wall Streett Pitt .
Storytelling among humans is at least 40,000 years old, and it remains the most developed interface for transferring information. Storytelling makes investing compelling, understandable and fascinating. Last month, you may have read my story about a breakthrough idea about how two different fuel cells could complement each other.
It had nothing to do with any specific stock, and I mentioned none at the end of the article, but I am confident fuel cells are going to be very big in your life as we move away from petroleum-based energy. I want you to know about the trend toward fuel cells. It will make you a better investor.
As it turned out, my timing was fortunate. Honda Motor Co. recently showed off a sexy new prototype automobile that runs on the most plentiful element in the universe — hydrogen. But it doesn’t burn hydrogen in an internal-combustion engine the way a prototype Mazda did 15 years ago. That technology is old.
Honda’s surprise wasn’t the technology itself — auto companies like Mercedes and independent firms such as Ballard Power Systems have been experimenting with fuel cells for decades — it was the announcement that Honda will introduce a fuel cell auto you can buy in two years.
Tetsuo Iwamura, CEO of American Honda, said his concept car “hints at” a new direction for the company. Just when you thought the Nissan Leaf and the Chevy Volt and Tesla (TSLA) cars were the future, a Honda with a small tank of hydrogen shows up that can go 300 miles before it needs refueling, which takes three minutes.
The disruptive technology you think you see — the conversion of automobiles from internal-combustion engines to electrics — is not the big picture. That is yesterday’s big picture. Technology has already moved past the electric vehicle.
The truly disruptive trend is where the electricity to power these vehicles will come from. Who wants to rely on batteries? Who wants trely on batteries? Who wants to wait for a charge cycle? Who wants to worry about building enough new power plants or installing 50-amp, 220-volt circuits in our garages? Wouldn’t you rather make your own electricity on the fly? You can with fuel cells.
About ORBACTIVTM (oritavancin)
ORBACTIVTM (oritavancin) for injection received FDA approval in the U.S. in August 2014. ORBACTIV™ is the first and only FDA-approved single-dose IV antibiotic for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused or suspected to be caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin–resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis (vancomycin-susceptible isolates only).
The Marketing Authorization Application (MAA) submission for ORBACTIVTM to the EMA was based on the results of the SOLO I and SOLO II clinical trials which were randomized, double-blind, multi-center trials that evaluated a single 1200 mg IV dose of ORBACTIV™ for the treatment of ABSSSI in 1,987 patients, and assessed a large subset of patients with documented MRSA infection (405 patients). These trials demonstrated non-inferiority for the primary and secondary endpoints evaluating 1200 mg once-only IV ORBACTIV™ dose infusion, versus 7-to-10 days of twice-daily vancomycin (1 g or 15 mg/kg). ORBACTIV™approval in the US was also based on the results of the SOLO I and SOLO II clinical trials.
» Mechanism of action studies showed that Kevetrin strongly induced apoptosis by activation of Caspase 3 and cleavage of PARP. Kevetrin induced phosphorylation of p53 at Ser15 leading to a reduced interaction between p53 and MDM2, an ubiquitin ligase for p53 that plays a central role in p53 stability. Stabilized wild type p53 induced apoptosis by inducing the expression of PUMA. In addition, Kevetrin increased expression of p53 target genes such as p21 (Waf1), an inhibitor of cell cycle progression.
» Kevetrin also induced transcription-independent p53 mediated apoptosis. Kevetrin enhanced the phosphorylation of MDM2. Phosphorylation of MDM2 alters the E3 ligase processivity. Stable monoubiquitinated form of wild type p53, accumulates in the cytoplasm and interacts with BAK or BAX proteins in mitochondria to induce apoptosis Thus Kevetrin activates both transcription dependent and transcription independent pathways to promote apoptosis.
Also: from The University of Texas MD Anderson Cancer Center
xosomes, tiny, virus-sized particles released by cancer cells, can bioengineer micro-RNA (miRNA) molecules resulting in tumor growth. They do so with the help of proteins, such as one named Dicer. New research from The University of Texas MD Anderson Cancer Center suggests Dicer may also serve as a biomarker for breast cancer and possibly open up new avenues for diagnosis and treatment. Results from the investigation were published in Cancer Cell.
"Exosomes derived from cells and blood serum of patients with breast cancer, have been shown to initiate tumor growth in non-tumor-forming cells when Dicer and other proteins associated with the development of miRNAs are present," said Raghu Kalluri, M.D., Ph.D., chair of the department of cancer biology at MD Anderson. "These findings offer opportunities for the development of exosomes-based biomarkers and shed insight into the mechanisms of how cancer spreads."
Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review.
Trafficking of biological material across membranes is an evolutionary conserved mechanism and is part of any normal cell homeostasis. Such transport is composed of active, passive, export through microparticles, and vesicular transport (exosomes) that collectively maintain proper compartmentalization of important micro- and macromolecules. In pathological states, such as cancer, aberrant activity of the export machinery results in expulsion of a number of key proteins and microRNAs resulting in their misexpression. Exosome-mediated expulsion of intracellular drugs could be another barrier in the proper action of most of the commonly used therapeutics, targeted agents, and their intracellular metabolites. Over the last decade, a number of studies have revealed that exosomes cross-talk and/or influence major tumor-related pathways, such as hypoxia-driven epithelial-to-mesenchymal transition, cancer stemness, angiogenesis, and metastasis involving many cell types within the tumor microenvironment. Emerging evidence suggests that exosome-secreted proteins can also propel fibroblast growth, resulting in desmoplastic reaction, a major barrier in effective cancer drug delivery. This comprehensive review highlights the advancements in the understanding of the biology of exosomes secretions and the consequence on cancer drug resistance. We propose that the successful combination of cancer treatments to tackle exosome-mediated drug resistance requires an interdisciplinary understanding of these cellular exclusion mechanisms, and how secreted biomolecules are involved in cellular cross-talk within the tumor microenvironment.
Bao Sarkar, Department of Pathology, Wayne State University School of Medicine, 4100 John R, HWCRC 740, Detroit, MI, 48201,
PMID: 23709120 [PubMed - indexed for MEDLINE] PMCID: PMC3843988
The deal, with Meiji Seika Pharma and Fedora, gives Roche the ex-Japanese rights to OP0595, a Phase I beta-lactamase inhibitor. The drug works in tandem with traditional antibiotics to break down treatment resistance and fight severe infections caused by Enterobacteriaceae, Roche said.
In exchange, Meiji and Fedora are getting an undisclosed up-front sum plus the promise of milestone payments tied to development and regulatory success, totaling as much as $750 million.
For Roche, buying into OP0595 is the latest move in its high-profile return to antibiotics. Like much of Big Pharma, the company gradually lost interest in the field years ago thanks to diminishing returns in R&D. But, considering the of-late escalation in hospital-acquired infections around the world and an alarmingly sparse pipeline across the industry, the drugmaker is splashing back into the space with multiple deals and development programs.
"There is an urgent need for new antibiotics able to combat the increasing resistance to antibiotics that is being seen worldwide," Janet Hammond, head of infectious diseases at Roche's pRED research operation, said in a statement. "Roche has a strong legacy in antibiotics and this collaboration demonstrates we are continuing to execute on our commitment. This beta-lactamase inhibitor has the potential for an expanded spectrum against multi-drug resistant bacteria and could be a much needed option for patients suffering from difficult-to-treat infections."
The latest deal follows a 2013 agreement with Polyphor in which Roche paid $40 million up front and promised up to $520 million more for a Phase II anti-infective. Last year, the company struck a deal with Discuva, borrowing the biotech's informatics-enabled discovery platform and pledging to pay up to $175 million per resulting drug.
As med tech companies home in on innovative ways to quell the growing Ebola outbreak, Aethlon Medical ($AEMD) snagged FDA approval for a clinical trial of its biofiltration device in patients with the virus.
The San Diego, CA-based company's Hemopurifier product filters viruses and toxins from the blood of individuals infected with Ebola, targeting antiviral drug resistance and serving as a first-line defense against the virus, the company said in a statement. Aethlon plans to launch an investigational study of the device at up to 10 U.S. clinical sites and enroll as many as 20 U.S. subjects in the trial. Therapy with the Hemopurifier will be administered to patients for 6 to 8 hours daily until their Ebola viral load drops below 1,000 copies/ml of blood.
Aethlon has already chalked up some promising results for its biofiltration therapy for Ebola, touting data presented in November at the American Society of Nephrology Annual Meeting that showed 242 million Ebola viruses were captured with the Hemopurifier during the treatment of a critically ill patient. The treatment also reduced the patient's Ebola viral load from 400,000 virus copies/ml of blood to 1,000 copies/ml of blood with no reported adverse events, the company said in a statement.
But the FDA's approval of a clinical study of the device does not come without a catch; in order to test its Hemopurifier in individuals with Ebola, Aethlon will have to distinguish results from a co-current trial of the product, which is being tested in individuals with hepatitis C who receive chronic dialysis. The company must report any adverse events from the new Ebola trial to the FDA within 10 working days of the device's use, Aethlon said in a statement.
CNIO Researchers Activate Hair Growth By Modifying Immune Cells
How to restore hair loss is a task not undertaken exclusively by beauty practitioners. The discovery, now published by a group from the Spanish National Cancer Research Centre (CNIO), reveals a novel angle to spur hair follicle growth. This also adds new knowledge to a broader problem: how to regenerate tissues in an adult organism, especially the skin.
The group has discovered an unexpected connection--a link between the body's defense system and skin regeneration. According to the authors of the study published today in PLOS Biology, cells from the immune system called macrophages-- those in charge of devouring invading pathogens, for example--are also responsible for activating skin stem cells and induce hair growth.
The regenerative ability of stem cells allows skin replenishment during a lifetime. But different factors can reduce their regenerative properties or promote their uncontrolled growth. When things go wrong, this can lead to aging and disease, including skin carcinomas. The discovery that macrophages activate skin stem cells may also have further implications beyond the possibility to develop therapeutic approaches for hair loss, but may also be relevant for cancer research.
The authors of the study are Mirna Perez-Moreno and Donatello Castellana, from the Epithelial Cell Biology Group of the BBVA Foundation-CNIO Cancer Cell Biology Programme, along with Ralf Paus, a hair immunobiology expert from the University of Manchester and Münster.
"We have discovered that macrophages, cells whose main function is traditionally attributed to fight infections and wound repair, are also involved in the activation of hair follicle stem cells in non inflamed skin," says Perez-Moreno.
I quote fromJoseph Wagner, Ph.D.
Chief Executive Officer
September 25, 2014
Some pumping going on, could be true, could be good science, or maybe later.
Multiple clinical studies reporting by year-end 2014,
coupled with very large market potential of products may
yield large, near-term valuation increases.
: Initial clinical validation studies on three diagnostic products reporting by
: Novel molecular cancer diagnostics that address major unmet medical
: Potential for rapid initial adoption through KOL support and limitations of
current diagnostic tests
:Potential for broad eventual adoption due to advantages over current
: Favorable reimbursement landscape with opportunity for value-based
pricing of tests
Near-term revenue potential (12-18 months)
: Potential for products to achieve “blockbuster” status ( $1B/year)
:A substantial proportion of the mammalian
genome is exclusively activated during
: These embryo-exclusive genes regulate:
- Cell proliferation
- Cell signaling
- Organ formation
:Many of these genes are accessed/activated by
cells after oncogenic mutation & transformation
: Many of these genes have not been previously
associated with cancer
The U.S. Environmental Protection Agency’s decision to postpone the release of its 2014 renewable fuel standard regulations will create uncertainty within the biofuels market and may cause investors to scuttle plans to build refineries in the U.S., biofuel advocates told reporters at a Nov. 24 briefing.
The standards—known as renewable volume obligations—set requirements for blending biofuels, such as ethanol, into gasoline at gasoline pumping stations.
EPA announced on Nov. 21 that it would not issue its 2014 renewable percentage standards until sometime in 2015. In addition, EPA will not finalize a controversial rule that would have made cuts to below 2013 levels for blending requirements, and enabled the EPA to waive the obligation requirements based on concerns about the distribution of renewable fuels to consumers.
Renewable fuel association officials said that EPA’s proposal, if made final, would have created a disincentive for producing and using biofuels. Brooke Coleman, Advanced Ethanol Council executive director, said “EPA’s decision to pull back the 2014 proposal is the right thing to do, but we need to move quickly in 2015” to get a better proposal in place.
EPA has said it plans to issue a proposal late in 2015. Bob Dinneen, Renewable Fuels Association president and CEO, said, “2015 is going to be another year of missed opportunities” unless EPA acts quickly in 2015.
The construction of refineries and supporting infrastructure has been a strong market for construction firms over the past several years. (ENR, 10/17/2011). A few commercial-scale, advanced biofuel refineries have opened in the past year, but the dozens of plants that are in the pipeline may be put on hold, or moved overseas, because of uncertainty about the future of the biofuels industry in the U.S., Coleman said.
The oil and gas industry, however, believes the entire Renewable Fuel Standard is problematic and should be scrapped.
Jack Gerard, American Petroleum Institute president and CEO, said in a statement, “The Renewable Fuel Standard was flawed from the beginning, horribly mismanaged, and is now broken."
He added, "Failure to repeal could put millions of motorists at risk of higher fuel costs, damaged engines and costly repairs.”
Gerard cited a Congressional Budget Office report that predicts higher gasoline and diesel costs under higher ethanol mandates. E15—a fuel blend with 15% ethanol—can damage engines and cause vehicles that use it to break down, according to Gerard's account of the Coordinating Research Council’s testing.
The American Fuel & Petrochemical Manufacturers went even further in response to EPA's announcement, calling the agency's inaction a "dereliction of responsibility." The group filed a notice on Nov. 21 saying it intended to sue EPA over its failure to to issue the 2014 regulations.
Sen. Lisa Murkowski (R-Alaska), the top Republican on the Energy and Natural Resources Committee, said, “With the agency responsible for implementing the standard now unable to finalize the rule for a calendar year within that year, let alone in accordance with statutory requirements, it is time for Congress to revisit and rethink this entire policy.”
But there is bipartisan support for the RFS and wider use of biofuels. In January 2014, a bipartisan group of lawmakers, including Sens. #$%$ Durbin (D-Ill.) and Chuck Grassley (R-Iowa), asked the EPA to modify its proposal to support “investments in the next generation of biofuels and the infrastructure necessary to deploy those fuels into the market.”
NeoStem presented the results from #$%$ sm#$%$ll study of c#$%$rdi#$%$c stem-cell ther#$%$py NBS10 #$%$t the Americ#$%$n He#$%$rt Associ#$%$tion #$%$nnu#$%$l meeting on Mond#$%$y.
Its Ph#$%$se 2 PreSERVE AMI (or #$%$cute myoc#$%$rdi#$%$l inf#$%$rction) Clinic#$%$l Tri#$%$l tr#$%$cked 161 p#$%$tient being tre#$%$ted #$%$nd h#$%$ving received six month follow-up for im#$%$ging #$%$nd 12 month medi#$%$n length follow up for mort#$%$lity, #$%$dverse events, serious #$%$dverse events (SAEs) #$%$nd m#$%$jor #$%$dverse c#$%$rdi#$%$c events (MACE).
Unfortun#$%$tely, NBS10, formerly known #$%$s AMR-001, w#$%$s no different th#$%$n #$%$ pl#$%$cebo #$%$t reviving blood flow through the he#$%$rt, #$%$nd it w#$%$s only slight better th#$%$n #$%$ pl#$%$cebo #$%$t preventing MACE in p#$%$tients studied. The drug is #$%$n #$%$utologous stem-cell ther#$%$py th#$%$t is t#$%$ken from #$%$ p#$%$tient’s own bone m#$%$rrow.
In theory, the stem cells received #$%$re then supposed to rebuild d#$%$m#$%$ged he#$%$rt muscle #$%$nd tissue #$%$nd get blood circul#$%$ting #$%$g#$%$in. But when p#$%$tients tre#$%$ted with #$%$n infusion of the drug underwent non-inv#$%$sive im#$%$ging to #$%$ssess blood flow through the he#$%$rt six months #$%$fter the tre#$%$tment, there w#$%$s no st#$%$tistic#$%$l difference between those tre#$%$ted with NBS10 #$%$nd those tre#$%$ted with #$%$ pl#$%$cebo.
Perh#$%$ps more concerning w#$%$s the d#$%$t#$%$ th#$%$t showed 17 percent of p#$%$tients tre#$%$ted with NBS10 still subsequently suffered #$%$ MACE event, only #$%$ slight dip from the 19 percent of p#$%$tients given #$%$ pl#$%$cebo.
Too b#$%$d, we #$%$re in #$%$ rut till positive results s#$%$ve lives.
If the ALNY GalNac-sirna delivery is so adverse then the downstream effect for RGLS can't be great one would assume.
Yet it is RGLS which was able to raise the needed capital and fully enrol for its upcoming trials. Which kind of negates any concerns an investor would have because of the regulatory approval required to get to that point.
Which brings us back to the question of why does Benitec have such a stringent control on its trial? The upshot being only two patients have been dosed. The second conveniently on the eve of the annual meeting.
My conclusion; it is because of serious toxicity concerns from the FDA.
November 15, 2014 at 4:05 PM
RES Americas plans large energy storage projects
Calling them the largest fully commercial energy storage projects in North America, renewable energy engineering and construction company Renewable Energy Systems Americas, Inc. (Broomfield, CO) will build two grid-scale, 19.8 megawatt (MW) energy storage projects in the Chicago area, the company announced on November 11. The Jake Energy Storage Center will be located in Joliet, while the Elwood Energy Storage Center will be located in West Chicago.
PARSIPPANY, NJ, USA I November 5, 2014 I The Medicines Company (NASDAQ:MDCO) today announced enrollment of the first patient in its Phase 3 clinical trial program for CARBAVANCE™ (meropenem/RPX7009), an investigational intravenous antibiotic under development for the treatment of serious bacterial infections due to gram-negative bacteria, particularly KPC (Klebsiella pneumoniae carbapenemase)-producing carbapenem-resistant Enterobacteriaceae (CRE).
CARBAVANCEis a combination of the carbapenem antibiotic, meropenem, combined with RPX7009, the first of a novel class of beta-lactamase inhibitors. Beta-lactamase inhibitors are agents that inhibit bacterial enzymes, which destroy beta-lactam antibiotics and result in resistance to first line as well as "last defense" antimicrobials used in hospitals. Gram-negative bacterial infections are widely considered to be one of the largest areas of unmet medical need, as these pathogens are growing increasingly resistant to existing therapies with few antibiotics in development.
The first CARBAVANCE clinical trial is designed to evaluate the efficacy, safety and tolerability of CARBAVANCE in approximately 850 patients with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP). The second trial is designed to evaluate the safety, efficacy and tolerability of CARBAVANCE in approximately 150 patients with suspected or known serious infections due to CRE across multiple indications.
Results from both CARBAVANCE Phase 3 trials are expected in 2016.
In January 2014, the U.S. Food and Drug Administration (FDA) designated CARBAVANCE as a Qualified Infectious Disease Product (QIDP). The QIDP designation provides CARBAVANCE priority review by the FDA, eligibility for the FDA's "fast track" status, and an additional five years of exclusivity upon approval of the product for intravenous use in six indications. These include complicated urinary tract and intra-abdominal infections, hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia, and febrile neutropenia.
Onxeo S.A.: Positive Phase II preliminary results of Validive® For the prevention of Severe Oral Mucositis in Head and Neck cancer patients.
Significant reduction of incidence of severe mucositis
Improved oral mucositis related symptoms and decreased adverse events related to radiotherapy
Good Safety profile
Strong Compliance to treatment
Trial Advisory Board validated data as supportive to enter into Phase III trial
PARIS, France & COPENHAGEN, Denmark I October 30, 2014 I Onxeo S.A. (Paris:ONXEO) (NASDAQ OMX:ONXEO) (Euronext Paris, NASDAQ OMX Copenhagen: ONXEO), an innovative biopharmaceutical company specializing in the development of orphan oncology drugs, today announced positive preliminary top-line results from its Phase II clinical trial of Validive® (mucoadhesive buccal tablet MBT clonidine Lauriad®) for prevention of severe oral mucositis (OM).
Onxeo has performed a large international randomized, double-blind, placebo-controlled Phase II trial comparing the efficacy and safety of Validive® 50 μg and 100 μg applied once daily to those of placebo in the prevention and treatment of chemoradiation therapy-induced severe oral mucositis in 183 patients with head and neck cancer.
Validive® was granted a fast track designation by the FDA in January 2014, allowing facilitated interactions with the FDA and optimized development time and review period for drugs investigated as treatments for serious or life-threatening diseases with a high unmet medical need.
Validive® is a therapeutic application of clonidine based on the mucoadhesive technology Lauriad®.
Clonidine stimulates the alpha-2 adrenergic receptors traditionally used to treat high blood pressure. It stimulates these receptors in the brain. This leads to a decrease in peripheral resistance and thus a lowering of blood pressure, as well as a reduction in heart rate and renal vascular resistance.
However, clonidine also acts as an agonist of the alpha-2 adrenergic receptors on leucocytes and macrophages, thereby decreasing the expression of the pro-inflammatory genes and the release of cytokines IL6, IL1β and TNFα. This effect leads to a reduction in the pro-inflammatory mechanisms. It also acts on the anti-inflammatory mechanisms by increasing the release of TGF β.
Clonidine therefore has the following properties:
Painkilling properties due to changes in the inflammatory response and its direct action on nociceptors;
Anti-inflammatory properties due to its action on the expression of the pro-inflammatory genes and the resulting release of cytokines IL6, IL1 β and TNFα and due to the release of TGF β.