Category Archives: Neurology

Roche SMA drug shines in study as costly new therapies advance

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A drug being co-developed by Roche to treat spinal muscular atrophy (SMA) helped improve development scores in babies with the genetic disease, a study released on Monday showed, as the race heats up for therapies destined to be among the drug industry’s most expensive.

PTC Therapeutics, which struck a licensing deal with Roche in 2011 for its SMA program, said more than 90 percent of babies with severe Type 1 SMA given the RG7916 drug achieved a greater than four-point increase in a test to measure their neuromuscular progress six months after treatment began.

PTC shares, which are listed on the Nasdaq, rose as much as 30 percent.

The companies hope their medicine, also known as risdiplam, will be approved to take on rival drug Spinraza from Biogen, which sells for $750,000 for the first year of therapy and about $375,000 annually after that.

Novartis is also quickly advancing in the SMA field with its $8.7 billion acquisition this year of U.S.-based Avexis that is working on a gene therapy for the disorder.

Analysts from Barclays project Novartis’s one-time treatment could run to $1.25 million per patient.

“We are delighted that up to 6.5-fold increase of protein production has translated into clinical impact for these babies,” PTC Chief Executive Stuart Peltz said in a statement about the RG7916 study, adding no babies required a tracheostomy or permanent ventilation since the study began, and no baby lost his or her ability to swallow.

SMA is an often-deadly genetic neuromuscular disorder caused by a missing or defective gene that normally produces a protein needed for development of motor neurons in the spinal cord. This leads to muscle wasting. Many babies with the severest form of the disorder die, while others never stand or walk.

Barclays analyst Emmanuel Papadakis expects that if Roche and PTC’s data holds up on RG7916 with regulators, it could become a fierce competitor to Spinraza, now the only licensed SMA therapy.

Cowen analysts also said on Monday they view PTC’s update as very encouraging for approval — and for competitiveness versus Spinraza, which is administered into the spine about four times a year. Roche’s and PTC’s drug is taken orally.

Novartis Chief Executive Vas Narasimhan also has high hopes for his own newly acquired SMA treatment, saying in April after the Swiss company bought Avexis that its gene therapy has “multi-billion dollar peak sales potential”.

SOURCE: www.pmlive.com/pharma_news

Prothena guts workforce by more than half, after trial failure

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Prothena Therapeutics has acted drastically by slashing staff numbers by more than half, after the failure of two pivotal trials for its lead candidate.

The company subsequently ditched NEOD001, when trials revealed that placebo treatment outperformed the drug candidate in the treatment of AL amyloidosis.

The reorganisation sees 63 positions cut away from the Dublin-based company, representing a shedding of 57% of the entire staff at the company.

As is usually the case, the process was necessitated to stymie cash losses during 2018 – it projected its estimated net cash burn for the year to be $40 million to $50 million, driven by a net loss of $170 million to $185 million.

Luckily for the biotech, it’s had some backers that were betting that its work would produce results and so estimates that it still have a relatively healthy $421 million in cash to end the year on.

One notable backer is renowned UK investor, Neil Woodford, who had to defend his investment in biotech in a blog post immediately after the trial failures were announced – pointing out strengths from within the Prothena’s pipeline and suggesting its partnership with Roche was one reason to keep faith with the biotech.

In the announcement regarding its restructuring, Prothena followed suit, with Gene Kinney, President and Chief Executive Officer of Prothena, saying: “As we move forward, we have the resources to support the advancement of our pipeline through meaningful milestones and we will focus on developing neuroscience programs that we believe have a potential to offer significant benefit to patients. This includes our two clinical-stage programs PRX002/RG7935, currently in Phase 2 development in the PASADENA study in patients with early Parkinson’s disease, and PRX004, which recently initiated a Phase 1 study in patients with ATTR amyloidosis.”

PRX002/RG7935 is both being developed in collaboration with Roche and there will be significant hopes placed on this candidate to pull the biotech out of a tricky spot; however, with the treatment being for patients with Parkinson’s disease, it’s a fairly risky bet given the dearth of disease-modifying treatments for the condition.

SOURCE: www.pharmafile.com/news/517476

ABPI expert urges to find new ‘blockbuster treatments’ for brain tumors

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With the Government set to invest an additional £20 million into the research, diagnosis and development of treatments for brain tumours, we need to talk more about how we are going to find the next blockbuster treatments for these devastating diseases.

Nearly 11,500 people are diagnosed with a brain tumour every year in the UK with fewer than 15% surviving beyond 10 years. This week’s announcement from the from the Department of Health and Social Care – following the death of Dame Tessa Jowell – that they would be doubling investment for brain cancer research to £40 million is a welcome commitment to helping achieve a goal our industry shares: finding innovative new treatments and cures for these diseases.

The science is advancing in laboratories here in the UK and around the world, funded and supported by charities, universities and the pharmaceutical industry, collectively we are working to fight back against this terrible disease.

Among the 7,000 medicines currently being developed by the global pharmaceutical industry, there are 58 medicines in the pipeline for brain tumours, including gliomas. Companies are actively working to find better ways to speed up medicines development to get treatments to patients sooner.

In her speech to the House of Lords in January, Dame Tessa Jowell talked candidly about her glioblastoma diagnosis and called for greater collaboration in the fight against cancer. She also talked about the speeding up of drug trials by testing more than one at a time, saying: “I am not afraid, but I am fearful that this new and important approach may be put into the ‘too difficult’ box.”

The type of clinical trials Tessa Jowell talked about have many different names: adaptive randomisation, drop-the-loser, adaptive dose-finding, adaptive seamless and the list goes on.

The one thing they all have in common is flexibility. In trials like this – that we call adaptive design clinical trials – researchers can see how patients are responding to treatments and then change or stop parts of the trial in real time.

When used appropriately, trials like this may improve efficiency, reduce cost, maximize information gained and minimize risk to the patients and sponsors. Ultimately, drug development can be accelerated so that the right treatments can be delivered rapidly to the right patients. The UK is seen as a pioneer of innovative clinical trials and this involves collaboration between academia, the NHS, industry and medical research charities –  we must ensure we keep it that way in the future.

The issue is that these clinical trial types are not easy to design, plan or execute. An adaptive design will not rescue a poorly planned trial or ineffective treatment.

We need to make sure the regulatory authorities in the UK are not seen as a barrier to innovation; the MHRA and HRA are open to discussion and we need to encourage researchers and pharmaceutical companies to start conversations with them early in the process of planning an innovative clinical trial.

We think that adaptive design clinical trials could be the solution to speeding up the research and development of not only brain tumor treatments, but for all sorts of diseases. Research into small or rare patient populations could really benefit from these trials since they help us quickly rule out the drugs or drug combinations that aren’t working and give more patients the option to contribute to research and clinical trials.

We’re not alone. In February, the Department of Health and Social Care published their brain tumor research report which stated that, because brain tumors are one of the areas that have small patient populations, we need to think differently about how we conduct clinical trials and incorporate innovative trial designs.

The report provided practical recommendations for how we can work collaboratively to make quicker progress in this area. The next steps are to build on the UK’s existing strengths, ensure we have access to researchers with the right skills, and make sure that the right infrastructure is in place for us to make really make progress in this area.

Alongside their funding announcement, we welcome the Government’s commitment this week to accelerate the use of adaptive design trials. When used appropriately, drug development can be accelerated so that the right treatments can be delivered rapidly to the right patients – and that’s where the real benefit lies.

As we look to the future of cutting-edge research and development for blockbuster treatments, we know we need to make the case for innovative clinical trial design, talk more about the amazing science our researchers, companies and NHS are pioneering and encourage them to have open conversations with the UK regulators to ensure that innovative clinical research is safe and effective.

Together, we won’t rest until devastating brain tumours are a thing of the past.

SOURCE: www.news-medical.net/news

Boehringer partners with Bactevo on drug discovery

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Boehringer Ingelheim is bolstering its drug discovery efforts with a new collaboration with UK tech-enabled research firm Bactevo.

Enabled by advance machine learning, Bactevo claims that its Totally Integrated Medicines Engine platform (TIME) will be able to bring about a paradigm shift in the speed, efficiency and quality of drug discovery, as well as dramatically enhanced safety profiling.

Aiming to identify novel small molecule lead compounds, the deal will see Bactevo use its TIME and synthetic chemistry technology to further enhance speed, efficiency and quality when detecting novel in vivo enabled leads.

In addition to working with partners to develop novel first-in-class medicines, Bactevo is also developing breakthrough medicines for the treatment of diseases that involve defects in mitochondrial function, such as MELAS and LHON. It is also targeting diseases of the central nervous system, such as Parkinson’s, Alzheimer’s and Amyotrophic Lateral Sclerosis (ALS).

Bactevo will receive upfront payments and research funding, although that specific amount was not disclosed at the time of writing.

The tech group could also be eligible to receive payments for certain research, development and commercialisation milestones.

David Williams, chief executive officer of Bactevo, said: “We are pleased to be commencing this highly complementary collaboration with Boehringer Ingelheim.

“It combines our cutting-edge TIME drug discovery platform with the powerful therapeutic drug development and commercialisation experience at Boehringer Ingelheim to create much needed new medicines in areas outside of our current therapeutic focus.”

SOURCE: www.pmlive.com/pharma_news

GSK’s blockbuster HIV drug linked with birth defects

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Regulators in Europe and the US have issued warnings about a link between GlaxoSmithKline’s blockbuster HIV drug Tivicay (dolutegravir) and birth defects of the brain and spine.

The European Medicines Agency’s safety committee has said it is evaluating preliminary results from a study which found four cases of birth defects such as spina bifida – a malformed spinal cord – in babies born to mothers who became pregnant while taking Tivicay (dolutegravir).

The Pharmacovigilance Risk Assessment Committee (PRAC) has issued precautionary advice while assessing the study, saying Tivicay should not be prescribed to women seeking to become pregnant.

Women who can become pregnant should use effective contraception while taking Tivicay-based medicines, the PRAC said.

In a separate announcement the FDA said it was also issuing a warning following preliminary results of an ongoing observational study in Botswana, suggesting women who took Tivicay at the time of becoming pregnant, or early in the first trimester, appear to be at higher risk for these birth defects.

The US regulator warned against stopping Tivicay-containing regiments without first switching to alternative HIV medicines, as this could cause the virus to spread to the unborn baby.

Women of childbearing age should talk to healthcare professionals about other non-Tivicay containing medicines.

Tivicay, an integrase strand transfer inhibitor (INSTI) is an important drug for GlaxoSmithKline, which produces the drug through its ViiV joint HIV venture with Pfizer and Shionogi.

Tivicay (dolutegravir) is sold on its own for use as a component of combinations involving other drugs, and generated sales of £1.4 billion,

And Triumeq, which combines dolutegravir with nucleoside reverse transcriptase inhibitors abacavir and lamivudine, brings in sales of more than £2.4 billion.

There are alternatives from the same class such as Merck & Co’s Isentress (raltegravir) and combinations, and combinations containing Gilead’s elvitegravir.

These are still preliminary findings, and the warnings have been issued purely as a precaution.

But preventing HIV spreading to unborn children is important to the medical community, and if there is stronger evidence of a link with birth defects, doctors will surely look for alternative therapies.

SOURCE: www.pharmaphorum.com/news

FDA approves new drug to treat MS in pediatric patients

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The U.S. Food and Drug Administration today approved Gilenya (fingolimod) to treat relapsing multiple sclerosis (MS) in children and adolescents age 10 years and older. This is the first FDA approval of a drug to treat MS in pediatric patients.

“For the first time, we have an FDA-approved treatment specifically for children and adolescents with multiple sclerosis,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Multiple sclerosis can have a profound impact on a child’s life. This approval represents an important and needed advance in the care of pediatric patients with multiple sclerosis.”

Gilenya was first approved by the FDA in 2010 to treat adults with relapsing MS.

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function and appearance of new symptoms, called relapses or flare-ups, are initially followed by recovery periods (remissions). Over time, recovery may be incomplete, leading to progressive decline in function and increased disability. Most people with MS experience their first symptoms, like vision problems or muscle weakness, between the ages of 20 to 40. Two to five percent of people with MS have symptom onset before age 18 and estimates suggest that 8,000 to 10,000 children and adolescents in the U.S. have MS.

The clinical trial evaluating the effectiveness of Gilenya in treating pediatric patients with MS included 214 evaluated patients aged 10 to 17 and compared Gilenya to another MS drug, interferon beta-1a. In the study, 86 percent of patients receiving Gilenya remained relapse-free after 24 months of treatment, compared to 46 percent of those receiving interferon beta-1a.

The side effects of Gilenya in pediatric trial participants were similar to those seen in adults. The most common side effects were headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain and pain in extremities.

Gilenya must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Serious risks include slowing of the heart rate, especially after the first dose. Gilenya may increase the risk of serious infections. Patients should be monitored for infection during treatment and for two months after discontinuation of treatment. A rare brain infection that usually leads to death or severe disability, called progressive multifocal leukoencephalopathy (PML) has been reported in patients being treated with Gilenya. PML cases usually occur in patients with weakened immune systems. Gilenya can cause vision problems. Gilenya may increase the risk for swelling and narrowing of the blood vessels in the brain (posterior reversible encephalopathy syndrome). Other serious risks include respiratory problems, liver injury, increased blood pressure and skin cancer. Gilenya can cause harm to a developing fetus; women of child-bearing age should be advised of the potential risk to the fetus and to use effective contraception.

The FDA granted Priority Review and Breakthrough Therapy designation for this indication.

The FDA granted the approval of Gilenya to Novartis.

SOURCE: www.news-medical.net/news/20180514

Allergan’s oral migraine drug closer to US filing

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Allergan has reported additional phase III results for its oral CGRP inhibitor ubrogepant, setting up a regulatory filing in the US next year.

New data keeps Allergan ahead of rival Biohaven

The positive read-out from its second pivotal trial for the acute treatment of a migraine attack showed a 50mg dose of ubrogepant was more likely to achieve a statistically significant reduction in pain two hours after administration – and another ‘most bothersome symptom’ (MBS), such as sensitivity to light or loud sounds or nausea – compared to placebo.

A lower 25mg dose also reduced pain but missed the mark on the MBS measure, according to Allergan, although it did show a trend towards improvement compared to the control group.

The company has reiterated that it is preparing to file the drug next year in the US, armed with the new data and an earlier study which showed significant efficacy across both endpoints for 50mg and 100m doses of the drug.

CGRP-targeting drugs look set to be the next wave of innovation in migraine treatment, with four companies vying for approval of intravenous or injectable candidates to be given either every month or every three months to try to prevent migraines occurring. Allergan’s drug is in the lead among a new group of orally-acting candidates – known collectively as ‘gepants’ – for acute use, in other words to try to provide relief of symptoms when an attack is already underway.

Novartis and Amgen are in pole position among the injectable CGRP-targeting drugs, with their Aimovig (erenumab) already filed and expected to gain FDA approval by May 17.

In Allergan’s new ACHIEVE II study, ubrogepant provided freedom from pain after two hours in 20.7% of the 25mg group and 21.8% of the 50mg group, compared to just over 14% of placebo-treated patients. The most bothersome symptom was relieved at that timepoint in 38.9% of the high dose group, 34.1% of low-dose patients and 27.4% of those on placebo.

The CGRP inhibitors offer hope to patients with severe chronic migraine who can’t get relief from the current array of therapies, which consists of pain-killing drugs, triptans and repurposed medicines such as the anticonvulsant topiramate or Allergan’s biggest and best-known product, Botox.

Analyst David Maris at Wells Fargo said Allergan’s new drug seems to offer triptan-like pain relief with an improved safety profile, and could be an option for an estimated four million people in the US with migraine who do not respond to or cannot tolerate triptan drugs, with blockbuster sales potential.

There were a few cases of raised aminotransferase levels (10 across the two studies at last count) – a potential market for liver toxicity – but according to Allergan are not judged to have been drug-related.

Ubrogepant’s nearest rival is Biohaven’s late-stage candidate rimegepant, which reported results from its phase III programme in March.

Allergan’s efforts to extend its migraine franchise suffered a setback when its inhaled drug Semprana (dihydroergotamine mesylate) was turned down by the FDA three times as an acute treatment for the disorder because of manufacturing issues. The programme is no longer listed in the company’s R&D pipeline.

SOURCE: www.pmlive.com/pharma_news

GW’s Epidiolex takes a leap toward US approval

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Shares in GW Pharma were given a boost after its cannabinoid Epidiolex took a giant leap towards US approval for treating seizures linked with Lennox-Gastaut (LGS) and Dravet syndromes.

According to briefing documents posted to the FDA’s website ahead of an advisory committee meeting scheduled for later today (Thursday), “the risk-benefit profile established by the data in the application appears to support approval”.

“In general, the risks associated with CBD treatment appear acceptable, particularly given the findings of clinical (effectiveness) in Lennox-Gastaut syndrome and Dravet syndrome, which are serious, debilitating and life-threatening disorders,” the authors note.

As no significant safety or efficacy issues were highlighted, it looks likely at this point that the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee will recommend the drug’s approval.

While the FDA is not required to follow the advice of its advisory committees it usually tends to do so, which indicates that marketing clearance for the drug seems likely. A final decision from the regulator is expected by the end of June.

Epidiolex is currently under review in both the US and the EU, the filings containing data from three Phase III trials showing that Epidiolex cut the monthly seizure rate in patients with Dravet syndrome or LGS, both rare and difficult to treat forms of childhood-onset epilepsy.

In one study, patients with LGS taking Epidiolex saw a median reduction in monthly seizures of up to 42 percent compared with a 17 percent drop for placebo.

In another involving children with Dravet syndrome, five percent became seizure free while taking the drug compared to none in the placebo arm, and patients also had a significantly greater median reduction in convulsive seizures (39 percent) compared to placebo (13 percent).

GW is reportedly working with the Drug Enforcement Administration to ensure it can legally market the cannabis-based medicine, though it contains less than less than 0.1 percent of tetrahydrocannabinol, the principal psychoactive constituent of the drug.

SOURCE: www.pharmatimes.com/news

Celgene bucks trend to strengthen neuroscience pipeline

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Celgene has gone against industry movement to back out of the neuroscience area by putting down a potential $2.2 billion to gain options on three drug candidates held by Prothena.

The deal sees Celgene pay $100 million up front, alongside buying $50 million in shares of Prothena, with milestone payments on the three drugs potentially racking up to a total payment of $2.2 billion.

Whether Prothena will see anything of this money depends on how well each clinical candidate performs in Phase 1 trials.

The neuroscience area has not been blessed with a huge amount of good news of late, with Pfizer pulling out of the space and a raft of Alzheimer’s drugs flopping. Celgene backing the area as a long-term investment is welcome news, particularly in regards to Alzheimer’s research, with fears it could begin to flag after so many failures.

One of the candidates is a protein that targets tau. The build-up of tau protein in the brain is one hypothesis about how best to treat the degeneration linked with Alzheimer’s disease.

Prothena commented in the press release that it has “identified antibodies targeting novel epitopes on the tau protein with the ability to block misfolded tau from binding to cells and to inhibit cell-to-cell transmission, preventing downstream functional toxic effects.”

This could be of huge interest, after a number of the other major alterantive hypothesis, amyloid-targeting Alzheimer’s treatments, failed to show efficacy in trials.

The other named target was the protein, TDP-43, which is associated with amytrophic lateral sclerosis and dementia. There is one other protein that Prothena has chosen not to name as being a target, though this is still within the neuroscience space.

“Prothena has a legacy of innovation in neuroscience and a team with a deep understanding of biological approaches that target protein misfolding disorders. Our collaboration leverages each company’s core expertise in protein homeostasis and protein clearance to target proteins that are the underlying cause of many neurodegenerative and orphan diseases. The programs we have chosen to collaborate on have the potential to provide foundational assets from which we can build new therapeutic approaches to these currently untreatable neurological disorders” said Richard Hargreaves, PhD, Corporate Vice President Neuroscience and Imaging for Celgene.

Should Celgene choose to take any of these candidates further than Phase 1, it will be responsible for all global clinical development and commercialisation. Prothena will, in return, receive $80 million per candidate picked up.

SOURCE: www.pharmafile.com/news/516844

Medicinal cannabis is safe and effective — it’s time to reboot research

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Researchers are calling for medicinal cannabis to be properly established in our modern medical arsenal.

Researchers claim that medicinal cannabis is safe and effective in pain relief, and are calling for the treatment to be properly established in our modern medical arsenal.

Cannabis has been used for centuries in pain relief, as a sleep aid and for many other purposes, yet there is little evidence on its safety and effectiveness. This is in part due to relatively recent legal restrictions on its use, which have hampered research efforts and resulted in doctors having little to no understanding of its use.

However, there has been an explosion in the number of studies published since 2012. The review provides two major studies on the use of cannabis in cancer patients and the elderly, as well as a comprehensive overview of the evidence, regulations, ethics and practical use. The authors and editors call for more research to improve the evidence base.

In a study led by Professor Victor Novack, A Professor at Ben-Gurion University of the Negev in Israel a team of researchers analysed data collected during the medicinal cannabis treatment of 2,970 cancer patients between 2015 and 2017. The two main problems patients were hoping to overcome were sleep problems and pain, and cannabis has been shown to be effective in alleviating both 95.9 percent of the patients reported an improvement in their condition.

The same team also analysed the effectiveness of medical cannabis in elderly patients who were being treated in 2015-2017 for a variety of issues, including pain and cancer. The researchers conclude in their paper: “Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population. Cannabis use may decrease the use of other prescription medicines, including opioids. Gathering more evidence-based data, including data from double-blind randomised controlled trials, in this special population is imperative.”

In a review Professor Donald Abrams at University of California San Francisco Ward covers 10,000 scientific abstracts, “concluded that there was conclusive or substantial evidence that cannabis or cannabinoids are effective for the treatment of pain in adults; chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis.”

Yet the report also highlighted the barriers to research in the US, which may explain the lack of strong evidence for the therapeutic use of cannabis. This dearth of research has also led to numerous ethical issues in prescribing cannabis, not least because many doctors do not understand the treatment enough to advise dosage and use. An article by researchers at the University of British Columbia, Canada and International Cannabis and Cannabinoids Institute, Prague, Czech Republic provides practical guidance for doctors, with data on cannabis pharmacology.

“We feel it is absolutely imperative to not only present the current state of affairs but also propose the development of the scientific research program within the paradigm of evidence-based medicine,” said Prof Novack,  “Our ultimate aim should be to scientifically establish the actual place of medical cannabis-derived products in the modern medical arsenal.”

SOURCE: www.europeanpharmaceuticalreview.com/news/73703