18 September 2018

Study finds daily aspirin does not reduce heart attack risk

Monash University in Australia has reported initial results from a large clinical trial (ASPREE) performed to investigate the benefits and risks of low, daily doses of aspirin in healthy people aged over 70 years.

The randomised, double-blind, placebo-controlled trial, funded by the National Institute of Health (NIH) and led by the university, is being conducted in a total of 19,000 subjects in the US and Australia.

ASPREE trial showed that 100mg aspirin did not significantly decrease the risk of a first heart attack or stroke. However, it was observed that daily dose of the therapeutic does not extend disability-free life.

Meanwhile, the researchers observed a 3.8% increase in the number of serious bleeding cases among people taking aspirin, compared to 2.8% in the placebo arm.

Monash University Epidemiology and Preventive Medicine department professor John McNeil said: “Despite the fact that aspirin has been around for more than 100 years, we have not known whether healthy older people should take it as a preventive measure to keep them healthy for longer.

“These findings will help inform prescribing doctors who have long been uncertain about whether to recommend aspirin to healthy patients who do not have a clear medical reason for doing so.”

Professor McNeil added that the results do not apply to patients with existing disorders, such as a previous heart attack, angina or stroke. In such cases, aspirin is recommended as a good preventive medication.

In May this year, POINT trial funded by the NIH showed that a combination of aspirin and clopidogrel can reduce risk of a secondary stroke, heart attack or other ischemic event in certain stroke patients.

While previous studies indicated aspirin may prevent cancer over the longer term, ASPREE revealed a slight rise in deaths in this group. The researchers believe this requires additional analysis and follow-up.

The trial is being continued to assess further effects of daily aspirin on health of the participants.

14 September 2018

Brexit and the pharmaceutical industry

The UK Government has added to its list of industry-focused technical notices laying out its preparations for a possible no-deal Brexit. The updates primarily focused on the energy industry, but a guideline on the handling of drug precursor chemicals has been added to the five previously stipulated for the medical industry.

Drug precursors are chemicals used in both the illicit manufacture of narcotics and legally in a wide variety of industrial processes. Legally they are categorised into four groups: the most sensitive substances, pre-precursors, bulk chemicals, and finally, medicinal products containing ephedrine or pseudoephedrine.

In the event of a no-deal Brexit, EU rules over trade of drug precursor chemicals will apply to the UK. This means that UK manufacturers will have to apply for export and import licenses they currently need to trade with non-EU countries. The government estimates this will cost between £109 and £3,665.

The Association of the British Pharmaceutical noted that since some of the chemicals covered by the guidance ‘already come from non-EU countries,’ which means ‘the appropriate authorisations are already in place’.

However, the pharmaceutical body went on to say: “As with all other aspects of Brexit, our industry is making sensible preparations for all scenarios.

“This is one more example of why we want a deal — any unnecessary complication of trading practices between the UK and EU is in no-one’s interest.”

GlobalData senior analyst Thomas Moore said: “Currently, trade of restricted chemical substances with other European countries in and out of the UK generally does not require a license, with the exception of a handful of compounds. In the case of a no-deal Brexit, all restricted compounds will now require a license to purchase from or sell to other European countries.

“It is currently very normal for the drug supply chain to rely on the movement of restricted compounds to the UK from other European countries, meaning that this would affect a lot of drugs manufactured in the UK.

“This particular legislation is unlikely to cause significant delays in the supply chain itself, since most of the additional paperwork will be carried out during the purchase of the chemicals, rather than during transit. However, it will provide an increased cost burden on drug manufacturers, with a license registration cost of up to £3,655, as well as an additional cost of £24 per import or export, which could affect overall profit margins.”

The previous government guidelines regarding Brexit and the pharmaceutical industry focused on batch testing of drugs, ensuring the safe supply of blood and organs, and regulating clinical trials and marketing approvals of both drugs and medical devices.

14 September 2018

NIH’s new initiative to boost cures for sickle cell disease 

The National Institutes of Health (NIH) has launched a new initiative to expedite the development of genetic therapies to treat sickle cell disease.

The Cure Sickle Cell Initiative will leverage new genetic discoveries and technological advances to safely progress the ‘most promising’ therapies into clinical trials within five to ten years.

A genetic blood disorder, sickle cell disease is characterised by clogged blood vessels and oxygen deprivation that can lead to organ damage, severe pain and premature death.

Over the years, basic research has resulted in new curative genetic approaches such as genetic editing of bone marrow cells.

Under the Production Assistance for Cellular Therapies (PACT) programme, NIH’s National Heart, Lung, and Blood Institute (NHLBI) is working on producing cellular therapeutic products, including genetically modified cells.

With the new initiative, NHLBI will support the development of cell and genetic therapies resources, clinical trials, analyses of various management approaches, data repositories, and patient and advocate engagement activities.

Every year, NIH spends around $100m on sickle cell disease research. This year, NHLBI plans to offer an additional $7m to commence the initiative’s research and engagement infrastructure.

NHLBI director Gary Gibbons said: “Our scientific investments have brought us to a point where we have many tools available to correct or compensate for the defective gene that causes sickle cell disease. We are now ready to use these tools to speed up our quest for a cure.”

The initiative and its research partners intend to build a data warehouse of genetic therapies for the disease. They will also perform comparative analyses of therapeutic strategies in order to investigate clinical and cost effectiveness.

In addition, they plan to establish national networks to provide patients and providers with easy access to the research, clinical trials and other activities across the country.

13 September 2018

US Appeals Court upholds ruling on CRISPR patents in favour of Broad Institute

The US Court of Appeals for Federal Circuit has upheld an earlier ruling by the Patent Trial and Appeal Board (PTAB) in 2017.

The board found that the key CRISPR patents for the Broad Institute, which encompasses Harvard University and the Massachusetts Institute of Technology, and the University of California (UC) do not overlap.

Despite UC filing its CRISPR patent application before the Broad Institute, the latter secured its patent first in 2014.

The Broad Institute’s CRISPR patent covers the use of the gene editing technology in eukaryotic cells, whereas UC’s application covers all cells, both eukaryotic cells and prokaryotic cells.

The case centres on whether using CRISPR technology in eukaryotic cells was the obvious next step from a technique described in a 2012 paper by UC researchers.

The PTAB ruled in February last year that the CRISPR patent claims did not overlap. The Court of Appeals referred to this in its decision, saying: “The Board found that a person of ordinary skill in the art would not have had a reasonable expectation of success in applying the CRISPR-Cas9 system in a eukaryotic cell.

“It concluded, therefore, that if UC’s claims were prior art, they would not have rendered Broad’s claims obvious, so there was no interference-in-fact.”

The Court of Appeal concluded that: “The Board’s fact-finding as to a lack of reasonable expectation of success is supported by substantial evidence.

“The Board performed a thorough analysis of the factual evidence and considered a variety of statements by experts for both parties and the inventors, past failures and successes in the field, evidence of simultaneous invention, and the extent to which the art provided instructions for applying the CRISPR-Cas9 technology in a new environment.

“In light of this exhaustive analysis and on this record, we conclude that substantial evidence supports the Board’s finding that there was not a reasonable expectation of success, and the Board did not err in its determination that there is no interference-in-fact.”

In making its decision the court did not re-evaluate the evidence it simply asked ‘whether such evidence supports the findings that were in fact made,’ according to Circuit Judge Kimberly Moore.

The Broad Institute wrote in a statement: “The Federal Circuit made the correct decision in upholding the United States Patent Trial and Appeal Board’s ruling. The patents and applications of Broad Institute and UCB are about different subjects and do not interfere with each other. The PTAB decision was clearly supported by sufficient evidence and followed applicable legal standards.

“It is time for all institutions to move beyond litigation. We should work together to ensure wide, open access to this transformative technology.”

In its statement, UC wrote: “While disappointed that the court did not allow the interference to go forward to resolve this issue, we are gratified that the court acknowledged that the Doudna-Charpentier team’s publication of their work in a 2012 paper represented a “breakthrough in the art” of gene editing, by first showing how the CRISPR-Cas9 system can be used as genome-editing technology in any environment.

“The court did not address the question of who invented the specific use of CRISPR-Cas9 in eukaryotic cells and emphasized that its decision was “not a ruling on the validity of either” Broad’s or UC’s claims.

“The decision thus does not preclude other proceedings, either in the USPTO or in the courts, by which UC may seek to establish that it is the actual inventor of use of the CRISPR-Cas9 system in eukaryotic cells. Accordingly, we are currently evaluating our further legal options in the courts.”

13 September 2018

UK researchers develop non-antibiotic drug for tuberculosis

Researchers at the University of Manchester have formulated a non-antibiotic drug for the treatment of infection caused by Mycobacterium tuberculosis bacteria (MptpB), including antibiotic resistant strains.

The drug has been designed to target the bacteria’s defences, instead of the organism itself.

The bacteria secrete Virulence Factor molecules that prevent the body’s immune response against it. During the latest research, the team found that inhibition of the MptpB Virulence Factor will enable white blood cells to kill the bacteria ‘efficiently’.

A regimen to treat tuberculosis typically involves a combination of antibiotics over six to eight months. This may lead to side effects and includes a 20% risk of disease recurrence. The bacteria also become resistant to certain antibiotics.

The researchers said that the new drug targets MptpB, which is not similar to anything in humans, and hence cannot negatively affect the human cells.

As the drug does not directly target the bacteria, it is believed to have lower chances of resulting in resistance.

Project leader Lydia Tabernero said: “For more than 60 years, the only weapon doctors have been able to use against TB is antibiotics. But resistance is becoming an increasingly worrying problem and the prolonged treatment is difficult and distressing for patients.

“And with current treatments, there’s no guarantee the disease will be eliminated: antibiotics do not clear the infection and the risk of being infected with drug-resistant bacteria is very high.

“But by disabling this clandestine bacteria’s defences we’re thrilled to find a way that enhances the chances of the body’s immune system to do its job, and thus eliminate the pathogen.”

When tested in guinea pigs with acute and chronic infection at Rutgers University in the US, the new non-antibiotic drug was found to be effective and led to a significant decrease in the bacterial burden.

The researchers expect to evaluate the agent in humans within three to four years.

12 September 2018

Consort to develop delivery device for opioid overdose drug

UK-based Consort Medical has signed a contract to develop a new drug delivery device for US-based Opiant Pharmaceuticals’ OPNT003 therapeutic intended to treat an opioid overdose.

The partners will work to devise a ready-to-use intranasal nalmefene variant for the reversal of opioid overdose, which is known to cause the majority of deaths amongst adults below 50 in the US.

Under the agreement, Consort’s wholly owned divisions Aesica and Bespak will collaborate with Opiant to create a clinically Unidose Xtra device pre-filled with nalmefene.

Aesica will supply clinical samples and registration batches required by Opiant to conduct clinical studies and gain regulatory approvals.

After approval from the US Food and Drug Administration (FDA), both subsidiaries will produce and supply the Unidose Xtra device for commercial purposes.

Consort Medical CEO Jonathan Glenn said: “We are delighted to announce this agreement with Opiant which highlights our expertise in the nasal delivery of drugs and the value of our unique offering of providing both drug manufacturing and delivery capabilities alongside one another.”

After completing formulation studies for OPNT003, Opiant plans to launch a confirmatory pharmacokinetic study next year.

The company expects to file a new drug application for drug and intranasal delivery device combination in 2020.

Opiant Pharmaceuticals CEO Roger Crystal said: “OPNT003 has the potential to be a transformative treatment for opioid overdose, and Consort’s significant experience with and expertise in inhalation technologies will help support our lead product candidate through commercialisation.”

Opiant holds the complete commercial rights to the opioid overdose candidate. The company is funding development through a $7.4m grant provided by the National Institutes of Health.

10 September 2018

AstraZeneca and Amgen receive breakthrough status for tezepelumab

AstraZeneca and Amgen have received breakthrough therapy designation for tezepelumab to treat severe asthma, irrespective of an eosinophilic phenotype.

The indication allows use for patients on inhaled corticosteroids (ICS) and long-acting beta2-agonists therapy (LABA) with or without oral corticosteroids (OCS) and other asthma controllers.

Tezepelumab is designed to block thymic stromal lymphopoietin (TSLP), an epithelial cytokine associated with the initiation and persistence of airway inflammation.

Inhibition of TSLP is expected to prevent pro-inflammatory cytokines generation by immune cells, in turn preventing asthma exacerbations and allowing better disease control.

The activity of the drug in early stages of the inflammation cascade may allow treatment of wide patient populations with severe, uncontrolled asthma.

AstraZeneca chief medical officer and Global Medicines Development executive vice-president Sean Bohen said: “Tezepelumab is exciting because it has the potential to treat a broad population of severe asthma patients, including those ineligible for currently-approved biologic therapies.

“The breakthrough therapy designation will help us bring tezepelumab to patients as quickly as possible.”

The FDA reviewed data from the Phase IIb PATHWAY clinical trial that assessed efficacy and safety of three tezepelumab dose regimens as an add-on therapy.

Data showed significant decrease in the annual asthma exacerbation rate, when compared with placebo. The rates were 62%, 71% and 66%, respectively, for 70mg, 210mg and 280mg doses.

Amgen Research and Development executive vice-president David Reese said: “The Phase IIb PATHWAY trial data demonstrated tezepelumab’s promise as a novel therapeutic option for a broad population of patients with severe asthma, including those ineligible for currently approved biologic therapies.”

AstraZeneca and Amgen are currently evaluating tezepelumab in two studies in the Phase III PATHFINDER trial programme.

NAVIGATOR studies the efficacy and safety of regular administration of tezepelumab for 52 weeks in patients with severe asthma that cannot be adequately controlled by ICS.

SOURCE studies the drug’s efficacy for 48 weeks in patients who require continuous treatment with ICS in combination with LABA and chronic maintenance OCS therapy.

4 September 2018

US researchers find 8,000 new antibiotic combinations effective

Researchers at the University of California, Los Angeles (UCLA) have discovered that nearly 8,000 four and five-antibiotic combinations are more effective at treating their indicated conditions than previously thought.

The prevailing opinions of scientists have been that the combination of more than two medications would not be effective at killing harmful bacteria. The effects of such combinations are expected to be ‘too small to matter’ or there is the possibility that one drug would cancel out the benefits of another.

However, UCLA’s new research found that the combination of four or five existing drugs could slow the spread of antibiotic-resistant bacteria. The team expects the new discovery to help to improve efforts to protect public health.

UCLA ecology and evolutionary biology assistant professor Pamela Yeh said: “There is a tradition of using just one drug, maybe two. We’re offering an alternative that looks very promising.

“We expect several of these combinations, or more, will work much better than existing antibiotics.”

The researchers made a total of 18,278 four and five antibiotic combinations using eight drugs. They tested the groupings against E coli bacteria, and predicted their effectiveness prior to assessment.

It was observed that 1,676 four-drug and 6,443 five-drug combinations demonstrated more effectiveness than predicted.

However, the team also found certain combinations to be less effective than expected. These included 2,331 four-drug and 5,199 five-drug groupings.

The eight tested antibiotics had six different mechanisms. The researchers believe that this factor led to partial effectiveness of certain antibiotic combinations analysed.

UCLA ecology, evolutionary biology and biomathematics professor Van Savage said: “Some drugs attack the cell walls, others attack the DNA inside. Combining different methods of attacking may be more effective than just a single approach.”

The team added that while the results are promising in laboratory setting, additional research is required to evaluate their use in humans.

The next step for the UCLA researchers is to develop open-access software based on their research.

The software will be available to other scientists next year, and will facilitate analysis of various antibiotic combinations studied by the UCLA team. Other scientists can also input data from their own tests.

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