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Monday, September 2, 2019

Roche’s Xofluza shows treatment benefit in young kids

Roche (OTCQX:RHHBYannounces positive results from a Phase 3 clinical trial, MINISTONE-2, evaluating a single dose of an oral suspension formulation of Xofluza (baloxavir marboxil) for the treatment of influenza in otherwise healthy children aged one to less than 12 years old. The data were presented at the OPTIONS X congress in Singapore.
The study met the primary endpoint of a statistically significant proportion of participants with adverse events (AEs) or severe AEs up to day 29, demonstrating a safety profile consistent with the tablet formulation. Efficacy was comparable to Tamiflu (oseltamivir phosphate). Specifically, 46.1% of children receiving oral suspension Xofluza experienced at least one treatment-emergent AE versus 53.4% in the oseltamivir arm.
Xofluza reduced viral shedding (the period when the virus is actively reproducing) by more than two days compared to oseltamivir (median of 24.2 hours vs. median of 75.8 hours).
Key secondary endpoints were also met.
The FDA approved the tablet formulation of Xofluza in October 2018 for patients at least 12 years old. It was discovered by Shionogi (OTCPK:SGIOY). Roche owns global rights except Japan and Taiwan.

China expands drug bulk-buy program, puts pressure on pharma firms

China has expanded a pilot drug bulk-buying program to almost the entire country in an attempt to negotiate lower prices from drug manufacturers, heaping fresh pressure on multinational pharmaceutical companies and their domestic rivals.

The program rolled out last year saw 11 Chinese cities, including Beijing and Shanghai, band together behind a tender process to bulk-buy 25 types of drugs. This caused the price of some medicines to plunge over 90%, state news agency Xinhua said.
The scheme will be expanded to 25 provinces and regions, who will form a league to look for suppliers for these drugs that will be stocked at public hospitals as well as some military and private medical institutions, according to documents released on Sunday by the drug procurement branch of the Shanghai Healthcare Security Administration.
The drugs on the list include off-patent blockbusters that are made by Western pharmaceutical giants, but which have generics made by local players, such as Eli Lilly’s cancer treatment drug Pemetrexed, which is sold under the brand name Alimta, and leukaemia therapy Imatinib sold by Novartis as Gleevec.
The tenders for the two drugs in last year’s pilot program were won by Chinese drugmakers’ generic products.
Beijing’s nationwide expansion measure could add strains on multinational drugmakers to consider larger price cuts for their off-patent blockbusters, a move that they have tended to refrain from in order to maintain their premium brand image, analysts said.
The documents also cited that as many as three winners of the tender for each drug could obtain as much as 70% share of the government’s purchase volumes, while the sole winner of a tender could win up to a 50% share of purchase volumes.
Under the new expansion plan, only the provinces of Fujian and Hebei are not involved in the program on mainland China.
“The 11 cities [in the previous pilot program] accounted for a relatively low market share in China,” John Yung, head of Asia healthcare research at Citi, told Reuters. “But as for the 70% market in the entire nation, the pressure is different.”
Novartis and Eli Lilly offered to cut prices for Gleevec and Pemetrexed by about 30% in some provinces earlier this year, according to releases on local governments’ drug procurement websites.

Health warnings on individual cigarettes could lower smoking rates

A new study from the University of Stirling’s Institute of Social Marketing has found that simply adding the warning “Smoking kills” on each cigarette rather than just on the outer package has the potential to reduce the number of people who smoke significantly. The study was published in the journal Addiction Research & Theory on August 29, 2019.

Smokers were asked to describe how they felt about the individual warning on each cigarette, and overall there was a strong agreement that it could well deter young people who don’t smoke or are just beginning to smoke.
The Framework Convention on Tobacco Control states the principle of informing consumers about tobacco-related risks. This has mostly been achieved using statutory warnings on cigarette packages.
These warnings have become bigger and bolder over the years, and are often required to cover at least half of the display package area. However, individual cigarettes can be used to warn smokers of the dangers.
This approach is part of the Scottish government’s anti-tobacco campaign called “Raising Scotland’s Tobacco-free Generation”, which began in June 2018. Other action points include changing the color and composition of cigarettes.
The government of Canada has also published the results of their discussions on the proposal to label tobacco products, including individual cigarette-based warnings, in the first part of this month.
However, tobacco companies opposed the move, partly because there is no evidence that these warnings influence smokers to start, maintain or stop the smoking habit.

Studying the effect of changes to individual cigarettes

The present study looks at this aspect, exploring the way smokers respond to the warning on the cigarettes. Three older British studies have already looked at this area, among 11-16-year-olds, 16-24-year-olds, and 16-34 year-olds. The second group included both smokers and nonsmokers, while the third was composed only of smokers.
The participants were asked to compare regular cigarettes to those which were colored an ugly color (green) or had the warning on each stick. The consistent trend was lack of appeal, perception of harm, and a lower desire to smoke with the ugly or warning-mounted cigarettes. This has been confirmed by other studies of the same kind.
In total, the research included 120 smokers aged at least 16 years, in Glasgow and Edinburgh, in 20 small groups based on age, gender, and social stratum, how they felt about seeing the warning on every cigarette.
All the groups felt that this kind of warning had the potential to create some effect on themselves or on others. The primary gain from this technique is that the message is now visible to all the new and young smokers as well as those who don’t smoke yet.

How was the study helpful?

Both smoking and second-hand smoking are predicted to decline in countries which have adopted plain packaging. Similarly, the researchers in the current study have previously predicted that this would occur if cigarettes themselves display clear warnings.
With this approach, smokers say that seeing the warning on every cigarette prolongs the message for much longer since it is seen with every fresh cigarette taken from the pack, on half-smoked cigarettes in the ashtray, and on the cigarette in one’s hand while it is being smoked.
Another aspect of putting warnings on individual cigarettes is the negative image of smoking that it creates. Especially among females, smokers associated this display with depression, worry and fear, reducing the enjoyment of the experience of smoking. Many smokers, mainly those who were younger, said they smoked less of each cigarette, cut down on the number of cigarettes, or even quit.
This study suggests that the introduction of such warnings could impact the decision-making of these groups. It shows that this approach is a viable policy option and one which would – for the first time – extend health messaging to the consumption experience.”
Crawford Moodie, First Author
The warning may work in several ways: it forces smokers to confront the results of their choice upfront, reduces the appeal of smoking for those who haven’t yet begun, provides a much longer duration of warning, keeps reminding smokers of their risks with each cigarette, and precludes the possibility of avoiding the message. However, constant exposure may also wear down the intensity of the warning over a relatively short time.

Real-life responses

The qualitative nature of the study meant it explored individual responses as well as the mean trend. Several salient comments include:
On how smoking such a cigarette would look: “Someone who had been smoking for a long time and couldn’t give up. Didn’t have the willpower – older.”
On how others perceive the smoker in this case: “The main problem for me would be people being able to see. They’d question you more on it, like, ‘Why are you doing that?”
On the emotional response: “It’s not so bad between people who smoke cause you are in the same position, but if you were with friends who don’t smoke, it would be a bit embarrassing.” “Maybe gives you a wee (small) bit of a guilt trip as well cause you’re standing there with that in your hand and you’ve got kids to think about.”
On the stimulus to quit smoking: “A lot of people wouldn’t even smoke it, and you wouldn’t even get a couple of draws.” “I actually have reasons to quit and I’m just being reminded every single time that I smoke.”
And conversely, the truly addicted say: “Warnings are nae (not) going to make any difference to an ardent smoker.” This group, interestingly, was mostly male, mostly from lower social scales, and said that if they quit it would be to save money or for health reasons.
On the deterrent effect: “I think for new smokers looking at it, they’d be like ‘oh I don’t want to do that.” “It was cool, you know, to be doing it, but if there was a blatant message on the cigarettes, I think I was intelligent enough to go no way…. I didn’t know it was as bad.”
Cancer Research UK responded to the research with a statement:
Government anti-smoking campaigns and tax rises on cigarettes remain the most effective methods to stop young people starting smoking, but we need to continue to explore innovative ways to deter them from using cigarettes to ensure that youth smoking rates continue to drop. This study shows that tactics like making the cigarettes themselves unappealing could be an effective way of doing this.”
Journal reference:
Extending health messaging to the consumption experience: a focus group study exploring smokers’ perceptions of health warnings on cigarettes. Crawford Moodie,  Rachel O’Donnell, Joy Fleming, Richard Purves, Jennifer McKell & Fiona Dobbie. Addiction Research & Theoryhttps://doi.org/10.1080/16066359.2019.1653861.

Popular eyelash treatments tied to rise in eye infections and emergency procedures

Experts are warning that eyelash treatments are causing a surge in emergency eyelid procedures and serious infections. One of the most commonly reported problems is a condition known as blepharitis; a chronic inflammatory disorder of the eyelids that arises due to bacterial overgrowth on the eyelashes, explains Consultant Ophthalmic and Oculoplastic Surgeon Elizabeth Hawkes in a recent article.

Eyelash treatments are very popular in Britain

Research carried out by Huda Beauty demonstrated just how committed British women are to ensuring they enhance the appearance of their eyelashes. It revealed that as many as one in six women would prefer to give up chocolate or dating apps than give up their false eyelashes.
However, it seems that the glues, chemicals and dyes used to extent, tint or even perm the lashes soon begin to take their toll on eye health.

Eyelashes are there to protect the eyes

Hawkes suggests that women remember that eyelashes are there to protect the eyes from exposure to dust and chemicals and that a build-up of bacteria and debris on the eyelids can lead to “irreversible eyelash loss.” The red swelling that often affects the eyelid could even require an emergency procedure.
Eyelids are the guards of your vision and are lined with eyelashes which protect against dust and chemicals entering. With all of the eyelash enhancing treatments, it is very important to take good care of the eyelids to protect against this damage.”
Elizabeth Hawkes, Consultant Ophthalmic and Oculoplastic Surgeon

What is causing the damage?

The answer is quite simple. It basically comes down to a lack of care and hygiene when taking care of the eyelids while they are at increased risk for infection.
Eyelashes play a crucial role in the aesthetic appearance of the eyes and have a life cycle of approximately 4 months, but chronic build-up of biofilm and debris on the eyelashes and eyelids can also cause irreversible eyelash loss.”
Elizabeth Hawkes, Consultant Ophthalmic and Oculoplastic Surgeon
Keeping on top of removing the biofilm and debris is the only way to prevent infection. One medical device called BlephEx, which removes biofilm from the eyelashes and eyelids, can be used twice a year to help people keep their lashes clean.

Maintaining good eyelid and lash hygiene

People who suspect they have developed blepharitis will need to seek help from a professional who can recommend treatment. However, to minimize the risk of any further infections, it is essential to maintain general lid and lash hygiene.
Hawkes recommends using a cotton pad to gently remove any eye make-up. Contact lenses should be taken out first and the pad should be placed over a closed eye so that the cleaning product has time to soak into the eyelashes. Hawkes also advised against rubbing the eyes repeatedly since this can harm the cornea and potentially damage the structure of the eye.
More detail about the recommendations is given below:

Remove eye make-up before going to sleep

Hawkes says she is frequently asked how eye make-up should be removed and  which products it is best to use. Her advice is that it is not necessarily about which specific cleansing product you use, but more about the technique used.
For the upper lid, she recommends that the gentle pressing of the cotton pad over the closed eye is repeated two to three times, depending on how much make-up there is to remove.
For the lower lid, she recommends placing the pad on the under eye whilst looking up. “Be mindful that our eyelid skin is the most delicate skin on the face, so a gentle approach is key,” she says.
Failing to clean the eyelids properly can cause chalazions (styes) to develop. “Management involves hot compresses and massage four times a day, but persistent ones often need surgical removal,” says Hawkes.

Avoid rubbing the eyes

Rubbing the eyes can affect the cornea and eyelids and doing so repeatedly can even cause irreversible structural changes to the eyes, such as eyelid laxity. This can lead to various  problems, including excessive periocular lines, where the eyelid turns inwards or outwards. This can accelerate the ageing appearance of the eye region, warns Hawkes.

Remove contact lenses before cleansing

Contact lenses should be taken out before cleansing the eye. “Whilst most of the eye makeup remover products state they are safe with contact lenses, I always recommend removing your lenses first.”

SATI gene editing could replace CRISPR

The ability to edit genes within living cells and organisms at all levels, using tools like the well-known and powerful CRISPR-Cas9, is one of the most sophisticated and useful advances in modern biology. However, the technique has been limited by a myriad of safety concerns.
Now, scientists at the Salk Institute have developed a potential game changer in this field – a new gene editor called SATI (intercellular linearized Single homology Arm donor mediated intron-Targeting Integration). This tool addresses multiple limitations of existing gene editing platforms.
The study was published in the journal Cell Research on August 23, 2019.

It is not easy to change the genes within a living organism without causing harm. CRISPR-Cas9 can cut the DNA at a defective site and allow a new gene copy to be inserted, but in the process any number of inadvertent alterations could occur around the edges of the spliced segment, the effects of which are unknown and potentially lethal. Non-dividing cells are also notoriously difficult subjects for gene editing – but they make up most of the body’s tissues.
SATI is itself an advance on a new form of gene engineering also developed at Salk, called homology-independent targeted integration (HITI) which can introduce new genes into the DNA without having to cut out the old one. The technique uses an alternate DNA repair pathway to integrate the new DNA.
HITI, however, could not correct all mutations since it is not able to remove the defective segment from the DNA strand.
We sought to create a versatile tool to target these non-coding regions of the DNA, which would not affect the function of the gene and enable the targeting of a broad range of mutations and cell types.”
Mako Yamamoto, Senior Author
SATI uses either of two different types of DNA repair mechanisms to integrate an inserted DNA segment into the genome. This makes it much more versatile and less error-prone.
It can be used to fix different types of mutations, whether they involve the removal, replacement or addition of a part of the DNA strand, in a diverse spectrum of cells, in both dividing and non-dividing states.
Moreover, its target is the noncoding part of the DNA and thus it minimizes the possibility of introducing unwanted changes in the genome. Scientists hope to eventually use SATI to prevent genetic conditions like the neurologic disease called Huntington’s chorea which causes progressive paralysis and death, among others.
Normal DNA repair mechanisms will ensure the inserted minigene becomes part of the organism’s genome alongside the defective gene. It can thus exert the normal effects of the target gene without ever disrupting the rest of the genome, significantly reducing the harmful effects of the mutation. This is called “knock-in.”

Developing the technique

The scientists used a mouse experimental model which showed the effects of a single change in amino acid sequence within one specific protein, caused by a single point mutation where one nucleotide in the LMNA gene is replaced or deleted. This caused the mouse to show signs of aging very early in its lifespan, a syndrome called progeria. This mutation was not easily repaired with current genome-editing tools.
Using SATI, the researchers successfully inserted a good copy of the defective at the targeted site in a noncoding segment of the DNA, leaving the body to incorporate it into the normal DNA strand. This acts to produce the normal protein product, correcting the basic defect in progeria.
They found that the gene began to function normally, reversing the signs of aging, and increasing the lifespan of the mouse by 45%. In human terms, this is the equivalent of 10 more years of life!
From this successful proof-of-concept experiment, the scientists conclude that this method can be used to edit the genome for a wide range of applications. They plan to further refine and extend this technique, to enable its use in more cells at a time. They look forward to even better results as the procedure is optimized.
Journal reference:
Suzuki, K., et al. (2019). Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction. Cell Research (2019). https://doi.org/10.1038/s41422-019-0213-0.

Heart failure results could unlock key market for Farxiga – AstraZeneca

AstraZeneca doesn’t quite know why its diabetes drug Farxiga is also working in patients with heart failure – but what it does know is that, if approved in this new use on this basis, it could tap into a huge new market with a well-established drug.
Farxiga (dapaglifozin), also known as Forxiga in some countries, is already one of AstraZeneca’s top 10 biggest selling drugs based on its already approved uses in type 2 diabetes.
Sales increased by 14% to $726 million in the first half of the year, although this was slower than the growth seen in 2018 when sales grew at 30% to $1.39 billion.
AZ is not putting a figure on how much will be added to these sales if Farxiga is approved in heart failure – but the market for the drug in the new indication is substantial.
In an interview with pharmaphorum, Joris Silon, senior vice president of AZ’s cardiovascular, renal and metabolism business unit, said that around 64 million people are affected by heart failure globally.
Around half of these have reduced ejection fraction heart failure, where Farxiga has shown benefit in the DAPA-HF trial, from which the company revealed detailed results this weekend at the European Society of Cardiology in Paris.
There are also two phase 3 trials ongoing of Farxiga in patients with heart failure and preserved ejection fraction.
After announcing top-line results from DAPA-HF last month, AZ gave details of the trial at ESC, showing Farxiga reduced the composite of cardiovascular death or worsening of heart failure by 26%, and showed a reduction in each of the individual components of the composite endpoint.
In analysing each of the components of the primary composite endpoint, there was a 30% decrease in the risk of experiencing a first episode of worsening heart failure and an 18% decrease in the risk of dying from cardiovascular causes.
The results were highly statistically significant and Farxiga’s effect on the primary composite endpoint was generally consistent across the key subgroups examined.
In diabetes, the main effect of SGLT2 class drugs like Farxiga is caused by the drug’s ability to increase the amount of blood sugar excreted through the urine.
The precise mechanism is not clear, said Silon, who suggested there is some kind of feedback mechanism causing the cardiovascular benefit.
He said: “We believe there is a multitude of effects happening not just with the glucose. More research will be needed on this.”
AZ’s hope is that the drug will be an easy sell to doctors who may be considering prescribing it to patients who already have diabetes and are at high risk of a cardiovascular event and were perhaps considering using a SGLT2 competitor such as Eli Lilly/Boehringer Ingelheim’s Jardiance (empagliflozin).
Farxiga is the first in its class to produce results in heart failure outside of diabetes and there’s also a lot of supportive safety data from this and the many other trials that could AZ make the case for its drug, according to Silon.
Silon said: “Half of these patients have diabetes where the drug is currently indicated. It’s very safe to use, it definitely has the potential to change care.”

Roche’s Xofluza limits spread of flu virus, says new study

Roche’s new influenza drug Xofluza can dramatically prevent the spread of the virus when used as a preventive therapy, according to new phase 3 data.
Xofluza (baloxavir marboxil) is already approved to treat people infected with flu, but the new results make a case to extend its use to include healthy people at risk of contracting the virus such as household members.
The BLOCKSTONE study found that giving a single oral dose of Xofluza after exposure to someone with flu reduced the risk of developing the illness by 86% compared to placebo, and with the protection seen regardless of the flu strain involved.
All told, 1.9% of Xofluza-treated household members contracted flu after exposure, compared to 13.6% of the control group. The protective effect also came into play in people at greater risk of contracting the virus, such as young children, and Roche says its drug had a “placebo-like” side-effect profile.
Limiting the spread of the virus in this way could be an important step in curbing flu outbreaks and preventing the spread in the wider community, according to Roche’s chief medical officer Sandra Horning.
The BLOCKSTONE trial is “the first to show that Xofluza is an effective preventive treatment following exposure to the flu and we look forward to sharing these data with health authorities,” she added.
The prevention results come after Xofluza was shown to be effective in children in the MINISTONE-2 study reported in July.
Xofluza is a cap-endonuclease inhibitor that interrupts a mechanism used by the virus to hijack the messenger RNA transcription system in cells, switching off virus production, and became the first new-mechanism treatment for flu in more than 20 years when it was cleared by the FDA last year.
Roche is hoping the new drug can breathe new life into its flu franchise, represented by older neuraminidase inhibitor Tamiflu (oseltamivir). That was a $3 billion brand at its peak, but has slumped since patent expiry and brought in $333 million in sales last year.
Xofluza needs all the help it can get at the moment, with sales in the first half just $6 million as the new product contended in the marketplace with low-cost Tamiflu generics.
In its favour is that it can be delivered as a single dose, while Tamiflu and generic oseltamivir has to be taken twice-daily for at least five days.
Xofluza is also effective in lab studies against oseltamivir-resistant flu strains, and it outperformed the older drug in the CAPSTONE-2 trial in people at high risk of flu complications. An FDA verdict on the latter is due by 4 November.