Category Archives: Clinical Trials

Teva wins FDA OK for crucial migraine drug

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Vital to Teva’s turnaround, Ajovy will challenge Novartis/Amgen’s Aimovig.

Teva has secured US approval for migraine drug Ajovy, a key part of new chief execeutive Kåre Schultz’s turnaround plan for the company.

The FDA approved the CGRP inhibitor for the prevention of migraine in adults with either monthly or quarterly dosing, based on two phase 3 studies showing that it could reduce the number of migraine days over a 12 -week period compared to placebo.

Ajovy (fremanezumab) is the second CGRP inhibitor to be approved for marketing after Novartis and Amgen’s Aimovig (erenumab), which got the green light in May and is dosed monthly, and ahead of late-stage rivals from Eli Lilly (galcanezumab) and Alder Biopharma (eptinezumab).

Teva would have been earlier to market but the FDA review for its products was delayed by three months while it sorted out some manufacturing issues. With Lilly due to hear from the FDA any day now, potentially setting up a three-way marketing battle, the Israeli drugmaker will be hoping the three-monthly dosing option will be popular with doctors and patients – particularly as there seems to be little to separate the antibodies when it comes to efficacy.

In a statement, Teva said that it had set a list price of $575 for the monthly dose and $1,725 for the quarterly dose, giving an annual cost of $6,900 before rebates and discounts – exactly the same level as Novartis and Amgen positioned Aimovig, and in line with stablished therapies like Allergan’s Botox.

It is estimated that with discounts the annual cost of the drugs could be around the $5,000 mark. However, the US-based Institute for Clinical and Economic Review (ICER) said recently that – even at that lower price – the new drugs should only be used with prior authorisation and after other preventive options such as Botox and anti-epilepsy drugs like topiramate because their long-tern safety is still unclear.

It is estimated that more than 36 million people in the US suffer from migraines, with around 40% of these would be suitable for preventive treatment, and that has led some analysts to predict buoyant sales of the CGRP inhibitors.

GlobalData said recently that it expects the market for migraine drugs to grow at more than 10% a year to reach almost $9bn by 2026, with the prevention category driven by the injectable CGRP inhibitors.

”Market share is going to come down to…variables such as frequency of administration, position to market, and market access strategy,” according to GlobalData analyst Rahael Maladwala.

“Each drug has its own set of advantages; Aimovig will be the first to market, Eli Lilly’s has significant experience in marketing drugs, and an extensive sales force, while both of the other drugs have a quarterly dosing regimen compared to monthly.”

On balance, GlobalData is putting Aimovig out in front in 2026 given its first-mover advantage generating nearly $1.4bn in sales in the seven major pharma markets (US, France, Germany, Italy, Spain, UK, and Japan).  Teva filed Ajovy in Europe earlier this year, but here it will also lag behind Aimovig as Novartis and Amgen picked up EMA approval for their drug in July.

Analysts at Jefferies have suggested Ajovy could become a $500m product in 2022, which will go some way towards counteracting the decline in sales of Teva’s blockbuster multiple sclerosis therapy Copaxone (glatiramer acetate), its rapidly ageing cash-cow product.

Since Schultz took the helm last year, Teva has been shedding staff and restructuring the business to cut costs, selling off its women’s health business for almost $2.5bn in order to pay down a very high level of debt stemming from its $39bn acquisition of Allergan’s generics business Actavis in 2015.

Ajovy is one of 23 New Drug Application (NDA) approvals Teva is targeting between fiscal 2019 and fiscal 2023 to help replace Copaxone and drive top-line growth, along with other new products such as movement disorder therapy Austedo (deutetrabenazine).

SOURCE: www.pmlive.com/pharma_news

New C.diff drug to be tested on patients for first time

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A new drug aimed at treating potentially deadly Clostridium difficile (C. diff) infections is set to be tested on patients for the first time.

Glasgow-based life sciences firm MGB Biopharma (MGB) said it was preparing to launch a Phase II clinical trial of its anti-bacterial agent MGB-BP-3.

The trial is expected to involve 30 patients based in North America.

All have been diagnosed with C.diff-associated disease (CDAD).

C.diff infections can cause diarrhoea and fever.

They have been a major problem in hospitals around the world, with thousands of deaths in the US alone linked to the bug each year.

The bacteria are able to take over the gut when a course of antibiotics kills off the bugs that normally live there.

MGB’s announcement came after it raised £1.3m from investors for trials of the new drug, which was invented at the University of Strathclyde.

The funding round was led by Edinburgh-based Archangels, with co-funding from a range of sources, including the Scottish Investment Bank, Barwell and Melrose-based Tri Capital.

The cash supplements a £2.7m grant awarded earlier this year by Innovate UK.

MGB said its trial would “evaluate safety and tolerability, efficacy and in particular look for improvement in global (or sustained) cure rates”.

Chief executive Dr Miroslav Ravic said: “We are already witnessing renewed interest in our new anti-bacterial agent and its trial in key medical centres in North America where CDAD is particularly prevalent.

“This offers opportunities both to progress the study rapidly and to attract increased attention to the results for this important trial.”

The company said it was aiming to start the trials in areas of the US and Canada with a high incidence of CDAD early next year.

SOURCE: www.bbc.co.uk/news/

Celgene’s Otezla produces “meaningful benefits” beyond beyond traditional metrics in plaque psoriasis

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Celgene made its voice heard amongst the chorus of new psoriasis data emerging from the European Academy of Dermatology and Venereology (EADV) Congress in Paris, revealing that Otezla (apremilast) achieved “meaningful improvements” in outcomes of patients with moderate to severe plaque psoriasis that may not be captured by common metrics that focus only on skin clearance, such as the Psoriasis Area Severity Index (PASI).

“Only considering skin clearance may not fully capture the effect a treatment may have on an individual’s disease burden and its impact on daily life,” explained Dr Denis Jullien, Department of Dermatology and Venereology at Edouard Herriot Hospital, and an author of the study. “For example, itching, which is not accounted for by PASI, is cited by over a third of patients as their overriding quality-of-life issue. These new analyses of Otezla studies can help inform both prescribers and patients when evaluating treatment decisions.”

The new findings included a post hoc sub-analysis of the phase 3 ESTEEM 1 trial, examining moderate to severe plaque psoriasis patients who did not achieve a PASI score of 75 after either 32 or 52 weeks of treatment with Otezla during the trial. In this group, over half achieved a 50% reduction in PASI score over the same periods – findings that Celgene argues “may more reliably indicate clinically meaningful benefit” when taken together with disease-specific quality-of-life measures.

For example, the data showed that itching was reduced from baseline by around 30% during weeks 4 to 52 for those who started treatment of Otezla, and during weeks 20 to 52 in patients who were switched form placebo at week 16. Additionally, patients reported an increase of at least five points in the Dermatology Life Quality Index (DLQI) over the same period.

“The ESTEEM and UNVEIL clinical trials continue to provide important learnings about Otezla for the treatment of psoriasis as well as quality of life for people who live with this chronic condition,” said Volker Koscielny, Vice President of Global Medical Affairs, Inflammation & Immunology at Celgene. “These sub-analyses of UNVEIL and ESTEEM suggest that appropriate patients with moderate to severe plaque psoriasis who experience manifestations beyond skin may benefit from treatment with Otezla.”

SOURCE: www.pharmafile.com/news/518748

Can sugar pills actually relieve chronic pain?

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A sugar pill could benefit patients suffering from chronic pain with specific brain anatomy and psychological traits.

Doctors could begin to prescribe sugar pills for some patients suffering from chronic pain, based on their brain anatomy and psychology. The pills are said to reduce their pain as effectively as new powerful pain relief drugs.

Scientists from Northwestern University have shown that they are able to reliably identify patients with chronic pain, that will respond to a sugar placebo pill based on their brain anatomy and psychological characteristics.

The scientists also suggests that it’s not necessary to hide this from the patient.

“Their brain is already tuned to respond,” said senior study author Professor of Physiology at  Northwestern University Feinberg School of Medicine, Dr Vania Apkarian.

“They have the appropriate psychology and biology that puts them in a cognitive state that as soon as you say, ‘this may make your pain better,’ their pain gets better.”

“You can tell them, ‘I’m giving you a drug that has no physiological effect but your brain will respond to it,’” he said. “You don’t need to hide it. There is a biology behind the placebo response.”

For the study, 60 patients with chronic back pain were randomised into two groups. The first group did not know whether they received the drug or the placebo, and the second group included people who came to the clinic, but received neither the drug nor the placebo.

The scientists did not study the people receiving the real drug, instead focusing on those receiving the sugar pill. The second group was used a control.

Individuals who had a decrease in their level of pain had similar brain anatomy. The right side of their emotional brain was larger than the left, and they had a larger cortical sensory area than people who were not responsive to the placebo. Psychologically, these individuals were also emotionally self-aware, sensitive to painful situations and mindful of their environment.

The researchers mention three main potential benefits: prescribing non-active drugs rather than active drugs, eliminating the placebo effect from drug trials, and reducing healthcare costs.

“It’s much better to give someone a non-active drug rather than an active drug and get the same result,” Prof Apkarian said. “Most pharmacological treatments have long-term adverse effects or addictive properties. Placebo becomes as good an option for treatment as any drug we have on the market.”

“Clinicians who are treating chronic pain patients should seriously consider that some will get as good a response to a sugar pill as any other drug,” he concluded. “They should use it and see the outcome. This opens up a whole new field.”

The study was published in Nature Communications.

SOURCE: www.europeanpharmaceuticalreview.com/news/79045

Gilead, Galapagos JAK inhibitor clears phase II test

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A mid-stage trial of Gilead and Galapagos’ JAK1 inhibitor filgotinib has set up a phase III programme for the drug in ankylosing spondylitis as it chases down two already-marketed dugs from Pfizer and Eli Lilly – and a late-stage rival from AbbVie.

In the TORTUGA trial, filgotinib met its clinical objective of reducing disease activity scores compared to placebo in patients with AS, a severe form of arthritis affecting the spine, with more patients achieving the target 20% improvement with the drug (76%) than in the control group (40%).

The drug is also in development for rheumatoid arthritis (RA), ulcerative colitis and Crohn’s disease with phase III trials already underway in those indications and results due in the coming weeks.

The drug was generally well-tolerated in TORTUGA but one case of deep vein thrombosis gave investors some cause for concern, putting some pressure on Gilead and Galapagos’ share price yesterday before share staged a partial recovery.

DVT is a recognised side effect with Eli Lilly’s JAK1 inhibitor Olumiant(baricitinib), which finally made it to market for rheumatoid arthritis in Europe last year but was rejected in the US at its first filing attempt over the safety issue. Gilead said that in the phase II AS trial the patient had an inherited condition that raised the risk of blood clots and the DVT was not thought to be drug-related.

First-to-market JAK inhibitor Xeljanz (tofacitinib) from Pfizer has already achieved $1bn-plus sales in RA, and with Olumiant somewhat hamstring by the safety issue on its label analysts are viewing the tussle between filgotinib and AbbVie’s upadacitinib as the next big battleground in the JAK inhibitor market.

AbbVie is a little ahead in the race to market, with phase III data in hand showing that upadacitinib is more effective than AbbVie’s $18bn-a-year injectable TNF blocker Humira (adalimumab) in RA when it comes to clinical responses gauged by doctors and patients. Like filgotinib, upadacitinib is also being tested in a string of other indications, including psoriatic arthritis, Crohn’s disease, ulcerative colitis and atopic dermatitis.

The rivalry is particularly strong as AbbVie was formerly Gilead’s partner for filgotinib, before ducking out of the collaboration and throwing its weight behind its in-house candidate.

SOURCE: http://www.pmlive.com/pharma_news

Jazz’ Vyxeos wins EU nod for certain acute myeloid leukaemias

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Dublin, Ireland-based Jazz Pharmaceuticals will be celebrating news of European approval of its leukaemia drug Vyxeos.

The European Commission is allowing use of the drug to treat adults with newly diagnosed, therapy-related acute myeloid leukaemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

Vyxeos is an advanced liposomal formulation that delivers a synergistic molar ratio of daunorubicin and cytarabine, and is “the first chemotherapy to demonstrate an overall survival advantage versus the standard of care in a Phase III study of older adult patients” with these conditions, said Daniel Swisher, Jazz’ president and chief operating officer.

The application included clinical data from five studies, including the pivotal Phase III study, data from which was published in the Journal of Clinical Oncology in July.

The study hits its primary target showing a superior improvement in overall survival compared to an alternative chemotherapy regimen, with 9.6 months versus 5.9 months, respectively.

“AML is a rare cancer in Europe and patients with therapy-related AML or AML with myelodysplasia-related changes have a particularly poor prognosis compared to people with other forms of leukaemia,” said Professor Charles Craddock CBE, academic director, Centre for Clinical Haematology at University Hospitals Birmingham NHS Foundation Trust.

“Vyxeos is a new and clinically meaningful treatment option that provides a welcome advance for patients and health care professionals across the European Union.”

SOURCE: www.pharmatimes.com/news

Ionis/Akcea’s ultra-rare disease drug rejected by FDA

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The FDA has opted to refuse approval to Akcea and Ionis’ Waylivra (volanesorsen) for the treatment of the ultra-rare hereditary condition familial chylomicronemia syndrome (FCS), despite the submission of Phase 3 data from the largest-ever study of the disease.

The US regulator alerted the manufacturers via a complete response letter (CRL), originating from its Division of Metabolism and Endocrinology Products, but the reason for the rejection was not given. Submitted data had shown that Waylivra reduced triglycerides by 94% in patients compared to placebo, which raised levels by 18%

FCS is characterised by extremely elevated triglyceride levels in the blood – levels which can’t be adequately metabolised due to a deficiency off lipoprotein lipase; it severely impacts daily life and can cause a range of damaging conditions including unpredictable and potentially fatal acute pancreatitis, chronic complications due to permanent organ damage.

“We are extremely disappointed with the FDA’s decision. FCS is an ultra-rare and debilitating disease. Our disappointment extends to the patient and physician community who currently do not have a treatment available to them,” commented Paula Soteropoulos, Chief Executive Officer of Akcea Therapeutics. “We continue to feel strongly that Waylivra demonstrates a favourable benefit/risk profile in people with FCS as was reflected in the positive outcome from our Advisory Committee hearing in May. We will continue to work with the FDA to confirm the path forward.”

Dr Brett P Monia, Chief Operating Officer of Ionis Pharmaceuticals, added: “We are fully supportive of WAYLIVRA and the many patients, physicians and researchers who are working to provide the first therapeutic option for FCS, a truly life-altering disease that deserves a treatment.”

SOURCE: www.pharmafile.com/news/518434

LEO Pharma to develop and commercialise JW Pharmaceutical’s JW1601

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Denmark-based LEO Pharma has entered into a global licensing agreement to develop and commercialise South Korean JW Pharmaceutical’s JW1601 drug candidate in a deal worth approximately $402m.

Under the terms of the deal, LEO Pharma will get exclusive global rights to JW1601. However, JW Pharmaceutical will retain its exclusivity in South Korea.

JW Pharmaceutical’s JW1601 is a new drug candidate for the treatment of atopic dermatitis. It was developed by one of the company’s affiliates C&C Research Laboratories.

Last year, JW Pharmaceutical acquired the exclusive rights to develop and commercialise the drug candidate globally. An investigational new drug application for a Phase I clinical trial is expected to be submitted over the coming months.

JW1601 is designed to prevent the activation and migration of immune cells that cause atopic dermatitis. The therapeutic selectively targets the histamine H4 receptor and inhibits histamine signalling responsible for itching.

The anti-pruritic and anti-inflammatory effects are expected to deliver better efficacy, while the selectivity towards H4 receptor is expected to show a good safety profile.

LEO Pharma Global R&D executive vice-president Kim Kjoeller said: “At LEO Pharma, we continuously seek to expand our pipeline with new innovative solutions with the ultimate aim of bringing real life-changing medicines to the many patients we serve.

This compound is a perfect fit with our existing biologics currently in phase III (Tralokinumab) and phase I (LP0145) and our topical Delgocitinib currently in phase II.”

As part of the agreement, JW Pharmaceutical will receive an upfront fee of $17m, followed by up to $385m in stepwise development and sales milestones.

In addition to the milestone payments, LEO Pharma will pay royalties on net sales of the drug candidate.

SOURCE: www.pharmaceutical-technology.com/news

Researchers develop anti-nicotine addiction drugs

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Washington State University researchers have developed an array of drug candidates which they believe may help tackle addiction to nicotine.

The drugs, outlined in the Journal of Medicinal Chemistry, target CYP2A6, a liver enzyme which metabolises nicotine. The researchers aim to slow the process through which nicotine is metabolised by inhibiting CYP2A6. As such nicotine would last longer in the body and thus people would experience fewer cravings and withdrawal symptoms.

One of the researchers Dr Philip Lazurus explained that “Nicotine in the body will get metabolized and excreted and it can be a fast turnover in some people. What we are trying to do is prevent the turnover and metabolism of it.”

However blocking the enzyme CYP2A6 is in many ways the easy part. Making sure the inhibitor doesn’t interfere with other processes is much harder. As such with over 600 possible inhibitors the process became one of trial and error as candidates which affected other processes were gradually excluded. Nevertheless the researchers were able to narrow the list of potential candidates to just 18 different compounds.

Travis Denton, a former tobacco chewer who led the study commented: “I quit cold turkey and I know how hard it is. Would this have helped? I believe so, because again, the people who want to quit, really want to quit,” he said. “They just can’t because it’s too doggone hard. Imagine if you could take this pill and your jitters don’t come on as fast — it’s just super reinforcing to help you quit”

Once the drug candidates are verified as safe by the FDA, clinical trials can begin.

SOURCE: www.pharmafile.com/news/518432

Europe’s first allogeneic stem cell therapy rejected by NICE

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Cost regulators for the NHS in England and Wales have not approved funding for TiGenix and Takeda’s Alofisel – the first allogeneic stem cell therapy to be approved for use across the European Union – for use in Crohn’s patients.

The therapy (previously referred to as Cx601) was approved in March to treat complex perianal fistulas in adult patients with nonactive/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy.

Perianal fistulas, a common complication of Crohn’s disease, occur when an abnormal passageway develops between the rectum and the outside of the body, potentially leading to incontinence and sepsis. Complex fistulas, which are rare, are more treatment resistant than simple fistulas.

Alofisel (darvadstrocel) is a local administration of allogeneic (donor derived) expanded adipose-derived stem cells (eASCs).

In clinical trials underpinning the drug’s approval, patients receiving the treatment showing a 44 percent greater probability of achieving combined remission compared to placebo, while a follow-up analysis (at 52 weeks and 104 weeks post-treatment) confirmed sustained efficacy and safety, according to the firms.

However, in draft guidelines, the National Institute for Health and Care Excellence said Alofisel showed only a modest improvement in the proportion of people with complex perianal fistulas achieving complete remission compared with placebo in one clinical trial.

“Reliable follow-up results are only available for up to one year, so it is unclear how long the treatment benefit will last,” according to the guidelines.

Because of this, cost-effectiveness estimates are “highly uncertain” and the committee was unable to conclude on the most plausible cost-effectiveness estimate, NICE said.

SOURCE: www.pharmatimes.com/news