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The trial will have nearly 20,000 subjects, who will receive two doses of the vaccine 28 days apart or a placebo. 

The Vietnam Ministry of Health has granted approval to Arcturus Therapeutics for commencing the Phase IIIb portion of Phase I/II/III clinical trial assessing its Covid-19 vaccine, ARCT-154, against SARS-CoV-2 delta variant and other variants of concern.

The company has started dosing the subjects in the trial, which will enrol nearly 20,000 subjects.

They will be given either two doses of the vaccine administered at a gap of 28 days or a placebo.

The approval to progress to Phase IIIb trial comes after a review of positive safety data obtained from the initial 1,000 subjects who were part of the placebo-controlled, observer-blind Phase I/II/IIIa trial.

To date, the Phase I segment has concluded the priming vaccination series with two doses in 100 people, with 75 subjects being enrolled in the ARCT-154 group.

The Phase II and Phase IIa portions are underway, enrolling 300 and 600 subjects, respectively.

Arcturus Therapeutics president and CEO Joseph Payne said: “Initiation of dosing in the Phase IIIb portion of the study brings us one step closer to our goal of filing for EUA and making it available as quickly as possible.

“As a low dose vaccine targeting variants of concern, ARCT-154 has a differentiated profile compared to currently available vaccines and we believe that our programme has the potential to become a best-in-class option for Vietnam and many other countries around the world.”

The company, along with its manufacturing partner, Vinbiocare Biotechnology, plans to seek emergency use authorization (EUA) for the vaccine in Vietnam in December this year.

This August, Arcturus reported that Vinbiocare received approval from the Vietnam Ministry of Health to conduct Phase I/II/III trial of ARCT-154.

During the same month, Arcturus and Vinbiocare signed a collaboration agreement to build a manufacturing plant in Vietnam to produce the former’s experimental Covid-19 vaccines for supply and use in the country.

Paris, 16^th September 2021: Ahead of the first Pharmapack Europe to be held in nearly 18-months, Informa has released the results of its global drug delivery and packaging survey, with the USA once again leading ‘drug delivery and device innovation’, but lagging behind all major European nations on sustainability.

Pharmapack Europe, which will be held at Paris Expo, Porte de Versailles, 13-14 October (2021), is expected to welcome up to 5000 people and 360 exhibiting companies. To enable access for those unable to attend in person, the event is being hosted in hybrid format, with online content and networking running from 27^th September until 22^nd October.

“We are incredibly eager to welcome back the pharma packaging, drug delivery and devices community after a year in which pharma’s innovation has never been more prescient. Yet, our research also shows the pandemic has accelerated a number of important existing trends in terms of connected devices, sustainable supply chains and remote patient administration. What’s exciting is that that with Pharmapack returning, we can provide the vital connections the industry relies upon to drive forward innovations and supply chains in 2022 and beyond.” Sherma Ellis-Daal, Brand Manager for Pharmapack Europe.

In fact, the Pharmapack Innovation Index (scored out of 10) – a market perception measure of each country’s drug delivery and device innovation – shows that globally the industry increased its outlook with a near 2% overall rise since 2020. Significantly, while the USA (8.26) again tops the rankings – followed by Germany (7.69) and Japan (7.52) – India (6.62) was by far the biggest mover, gaining nearly 13% on its score from 2020. This is particularly impressive improvement as it follows on India’s 25% gain from its score in 2019.

Andy Fry, Founder, Team Consulting provided some context to the rapid improvements, adding: “There has indeed been a lot of activity and interest from Indian and Chinese organisations focused on developing lookalike models of existing European or US devices, including DPIs and soft mist inhalers. Such developments could well morph into completely new devices.”

One of the key drivers for Pharmapack as an organisation, throughout its agenda, is to help the industry focus its attention on improving its CO₂ impact and becoming more sustainable in its materials use and recycling. This year, Pharmapack launched its inaugural Sustainability Index (scored out of 10) – a measure of how far long each country is towards achieving optimal sustainability for devices and packaging – with European nations Sweden (6.87), Germany (6.74), Switzerland (6.78), France (6.09) and the UK (6.04) perceived to leading the industry on sustainability initiatives. Crucially, leading European market were well ahead of the United States (5.78), China (4.22) and India (3.30) – the latter two of which were scored particularly poorly by the industry executives surveyed.

One challenge that has been highlighted by experts recently is the dichotomy of the drive towards sustainability and the increased use of connected devices – which often prioritizes materials and patient adherence over utilizing greener material. However, encouragingly, our industry executives surveyed (65%) believe such tension will be short lived and that, in the medium term ‘a shift towards better recycling and improved product lifespan’ will help integrate sustainability goals without compromising smart device adoption over the next three years.

“The Pharmapack agenda reflects these concerns and will explore ‘patient-centred devices design’, ‘practical measure to improve sustainability’, ‘the impact of biosimilars on autoinjector development’ as well as the usual cutting-edge innovations in the Learning Labs and the Innovation Gallery. But 2021 is also a reimagining of the entire Pharmapack experience, with content and learning available in advance. For example, networking and targeting of contacts can take place in the two weeks before you arrive to pre-qualify leads. So, I encourage everyone to take maximum advantage of the resources available, as we are at an incredibly important moment for industry innovation,” added Ellis-Daal

Similarly, in the heart of the show floor will be the 2021 Start-up Hub, providing a space to learn about companies developing and expanding new technologies in packaging, labelling, drug delivery, device design and engineering. These innovative companies will present early-stage products and pitch them to a panel of experts in order to gain more exposure and network.

The full findings of the Pharmapack 2021 Report and Innovation Indies are available for download here. For more information on Pharmapack hybrid event and agenda please visit www.pharmapack.com

An artificial intelligence algorithm was able to detect signs of lung cancer on CT scans a year earlier than with traditional methods, according to a new study.

CT (computed tomography) scans are already used to spot signs of lung tumours, followed by a biopsy or surgery to confirm whether the tumour is malignant, according to Benoît Audelan, a researcher at France’s National Institute for Research in Digital Science and Technology.

Each scan involves a radiologist examining around 300 images and trying to spot tell-tale signs of cancer, which is a labour-intensive process that is hard to scale to national screening programmes.

Audelan and colleagues from the Université Côte d’Azur, the University Hospital of Nice and digital imaging software specialist Therapixel trained their AI using CT scans from 888 patients that had previously been examined by radiologists to identify suspicious growths.

They then put it through its paces on a new set of scans from 1,179 patients taken from a lung screening trial with three year follow-up, in which 177 cases of lung cancer were subsequently diagnosed.

The AI was able to correctly identify 172 of the 177 cancers, giving it 97% detection accuracy, with the cases it missed typically those near the centre of the chest which are harder to spot.

The team then analysed scans taken a year before the tumours were diagnosed in the same 1179 patients and it was able to identify 152 suspicious areas that were later diagnosed as cancer.

One problem to overcome however was a high rate of false positives, when the AI identified areas as suspicious that turned out later to be benign.

Audelan’s frank assessment is that this would need to be “vastly improved” before the AI could be used routinely in the clinic, as false positives would be followed by unnecessary biopsies.

Nevertheless, he said – while presenting the new data at the European Respiratory Society (ERS) meeting this week – that the results show the potential of using AI to make lung cancer screening quicker and more efficient, and ultimately help diagnose more patients at an early stage.

“Screening for lung cancer would mean many more CT scans being taken and we do not have enough radiologists to review them all,” he said.

“That’s why we need to develop computer programs that can help. The objective of our research is not to replace radiologists but to assist them by giving them a tool that can spot the earliest signs of lung cancer,” he added.

Lung cancer is the most common cause of cancer death with around 1.8 million lives lost around the world each year. Lung cancer is often diagnosed at a late stage when treatment is less likely to succeed.

A 20% to 25% reduction in staffing at the UK Medicines and Healthcare products Regulatory Agency (MHRA) risks undermining the ability of the authority to fulfil its role, according to trade unions.

In an open letter to health secretary Sajid Javid, Prospect, Unite and three other unions say the decision to slash the MHRA’s current 1,200 workforce by up to 300 workers means that “regulatory decisions may suffer”.

Fewer staff will therefore be asked to cover more ground with fewer resources, all while operating under a pay freeze, they claim.

The UK could end up facing “either long delays in approving new medicines or that the MHRA will be reduced to effectively ‘rubber stamping’ EU regulatory decisions”, according to the unions.

They also say the regulator is facing the double whammy of an increase in workload after Brexit and a reduction in revenue from its earlier work on reviewing medical products for EU member states, and that the UK government is failing “to replace this funding or introduce a sustainable financial model”.

The MHRA said earlier this year that it would be “transforming” the way it operates, with discussions involving unions ongoing and a formal consultation process due to be concluded in the late autumn. The job losses will affect different functions across the MHRA.

“This transformation is in response to four challenges: the UK exiting Europe (with a consequent reduction in the fee income we receive); our role in enabling the Life Sciences strategy; the recent Cumberlege review which recommended that we focus on patients in all our activities; and financial pressures,” said a spokesperson.

“We will continue to be a world-class regulator that delivers the right outcomes for patients, while we modernise the services we provide to industry, and remain financially stable.”

The letter argues however that any change must be evidence-based, and not simply led by financial considerations.

“Recent months have taught us the value of having a world class medical regulator that is able to respond quickly to emerging health challenges,” said Prospect general secretary Mark Clancy.

“It would be reckless to put this at risk by imposing such severe staffing cuts on the organisation.”

AbbVie has expanded its ophthalmology pipeline via a licensing deal with Regenxbio, paying $370 million upfront to get its hands on a gene therapy for wet age-related macular degeneration (AMD) and other eye diseases.

The partnership centres on RGX314, which delivers a gene coding for an antibody against VEGF – a well-established approach to treating wet AMD and the target of current blockbuster drugs like Bayer’s Eylea (aflibercept) and Novartis/Roche’s Lucentis (ranibizumab).

RGX-314 is currently in a pivotal, phase 2/3 trial investigating its safety and efficacy when it is injected as a one-off therapy under the retina of the eye in patients with wet AMD, comparing it to regular intravitreal injections of Lucentis.

Regenxbio is also running a pair of phase 2 trials in patients with wet AMD and diabetic retinopathy in which RGX-314 is administered into the suprachoroidal space – a procedure that can be carried out in a doctor’s office rather than in surgery.

AbbVie is also putting up $1.4 billion in potential milestones for the project, and the two companies will split the costs of any additional studies.

The companies hope that the one-shot therapy could free patients from requiring injections into the eye every few weeks, and maybe even allow earlier treatment of people with the eye diseases.

If approved, RGX-314 could follow a path already trodden by Luxturna (voretigene neparvovec) from Spark Therapeutics (now part of Roche), which became the first gene therapy to be approved by the FDA in 2017, getting a green light to treat of patients with vision loss due to form of inherited retinal dystrophy (IRD) in 2017.

Luxturna hasn’t met its original sales expectations, causing Roche to take a CHF 81 million charge last year, but AbbVie and Regenxbio are hoping for much more from RGX-314 if approved, not least because it is being developed for diseases that are much more common.

RGX-314 is delivered using an adeno-associated virus (AAV), a vector whose safety has been thrown into spotlight of late by a recent clinical hold for Biomarin’s gene therapy for phenylketonuria after liver tumours were seen in animal studies.

Last week, FDA advisors mulled over the safety of gene therapies, and while they called for more careful monitoring of subjects in trials stopped short of recommending any additional restrictions on  studies.

Under the terms of the AbbVie deal, Regenxbio will share profits from net sales of RGX-314 in the US if it reaches the market, picking up royalties elsewhere, and is also holding on to an option on certain commercial rights in the US. The transaction is expected to close by the end of 2021.

Itamar Medical was on the acquisition trail itself earlier this year, buying Spry Health to extend its sleep sensor technology range. Now, it’s being snapped up Zoll Medical in a deal valued at around $538 million.

Israel-headquartered Itamar markets a sensing device called WatchPAT that attaches to the finger during sleep, measuring vital signs like heart and breathing rate, oxygen levels in the blood to monitor for signs of sleep apnoea in the home rather than a sleep clinic.

It made sales of almost $13 million in the second quarter, a rise of 41%, with WatchPAT accounting for around $10 million of that total.

The takeover of Spry in January kicked off a programme to develop a watch-like wearable for detecting sleep apnoea that – unlike WatchPAT, which is used over a single night – could be worn over weeks or even months.

The company is also working on other digital technologies and at SLEEP 2021 introduced a SleePath dashboard that enables data to be collected from the patient through a smartphone app before and after the home sleep test.

Zoll Medical intends to offer Itamar’s platform alongside its range of cardiovascular products, which includes wearable heart monitors and defibrillators, as well as Remede, a neurostimulation implant for sleep apnoea that has just recently been approved by the FDA.

The US-based company – a unit of Japanese group Asahi Kasei – acquired Remede when it bought its developer Respicardia in April for an undisclosed sum.

Zoll Medical chief executive Jon Rennert said that merging with Itamar “will help more patients receive diagnosis and treatment for sleep-disordered breathing”. Itamar’s shares leaped more than 40% after the agreement was announced.

The $31-per-share deal is expected to be closed by the end of this year, subject to approval by the shareholders of Itamar, regulatory approvals and other usual closing conditions

Sleep apnoea is particularly prevalent in people with underlying cardiovascular disease, and affects around 54 million people in the US alone. It is caused when relaxation of the muscles in the throat cause the airway to narrow, reducing the amount of air taken in and out with each breath.

Sometimes the airway can be shut off completely, and in severe cases, apnoea episodes can occur hundreds of times a night, each causing a brief period of wakefulness or shallower sleep. It can lead to other health problems, including high blood pressure, heart attack, stroke and diabetes.

Researchers in the UK are working on an artificial intelligence (AI) algorithm to help diagnose deep vein thrombosis (DVT) from ultrasound images – and potentially prevent patients from receiving drugs unnecessarily.

The team from Oxford University, Imperial College London and the University of Sheffield are working with German tech company ThinkSono on the smartphone-based app, called AutoDVT, and estimate it could cut the cost to health services of each examination by up to $150.

DVT is a blood clot most commonly found in the leg, which can lead to fatal blood clots in lungs and is associated with long-term symptoms and disability in 30-50% of patients. It is usually diagnosed using compression ultrasound, interpreted by a trained radiographer.

Unfortunately, up to 90% of patients with possible symptoms are not found to have a DVT on imaging, which contributes to long waiting lists for scans and a heavy workload for specialists.

A study of the AI published in Nature Digital Medicine suggests that the AI algorithm accurately diagnosed DVT when compared to the gold standard ultrasound scan. This is the first study to show that machine learning algorithms can potentially diagnose DVT, according to the researchers.

The open label study trained the AutoDVT app on 255 volunteers, and then assessed it against 53 patients with or without a previous diagnosis of DVT, to give a preliminary sense of its sensitivity and specificity. The scientists also modelled the potential cost-effectiveness of the system using NICE criteria.

“We have found that the preliminary data using the AI algorithm coupled to a hand-held ultrasound machine shows promising results,” said study lead Dr Nicola Curry of Oxford University.

“Currently, many patients do not have a definitive diagnosis within 24 hours of a suspected DVT, and so many patients end up receiving painful injections of what can often be an unnecessary anticoagulant, with potential side effects,” she added.

The hope is that AutoDVT will get the right diagnosis faster to the nearly 8 million people worldwide who potentially have a venous blood clot each year, according to the researchers.

The researchers are now working on a blinded study that will compare the accuracy of AutoDVT with standard care to give a more robust assessment of its ability to pick up DVT cases.

“The AI algorithm can not only be trained to analyse ultrasound images to discriminate the presence versus the absence of a blood clot,” commented study team member Christopher Deane from the Oxford Haemophilia and Thrombosis Centre.

“It can also direct the user using the ultrasound wand to the right locations along the femoral vein, so that even a non-specialist user can acquire the right images,” he added.

The first patient has received a low dose of Beckley Psytech’s psychedelic medicine psilocybin in a clinical trial for short-lasting unilateral neuralgiform headache attacks (SUNHA), a rare disorder.

The UK company says that SUNHA is a debilitating condition that is estimated to affect 40,000 patients in US and Europe. It is characterised by short, extremely painful headaches that can occur many times a day, and there is currently no approved treatment for the condition.

The phase 1b trial should generate results in early 2022 and is something if a departure for the use of psychedelic medicines, which are typically being tested at higher doses in carefully controlled environments and alongside psychological therapy for indications like depression and post-traumatic stress disorder (PTSD).

In April, for example, researchers at Imperial College London’s Centre for Psychedelic Research reported that a psilocybin formulation developed by Compass Pathways was more likely to help patients achieve remission from depression than a widely-used antidepressant medicine.

In this latest study, psilocybin – the active ingredient in magic mushrooms – is being administered as a straight pharmacological intervention, at a range of doses that are expected to be too low to cause hallucinogenic effects.

It will enrol up to 12 patients to try to show proof of concept and – if successful – the recommended dose to take forward for further development. Patients will receive doses on days one, six, and 11, with a follow-up visit on day 25.

It will explore the change in frequency, duration, and intensity of headache attacks with psilocybin treatment, as well as the drug’s effects on cognition in people with chronic SUNHA, as well as safety and tolerability.

At the moment, SUNHA is generally treated off-label using epilepsy medicines like lamotrigine, topiramate and gabapentin, but there is limited data backing their efficacy.

“The potential medical advantages of psychedelic agents, such as psilocybin, could be transformational to the quality of life for those affected by this disease,” said Cosmo Feilding Mellen, chief executive of Beckley Psytech.

The UK company recently raised an impressive £58 million (around $80 million) in an oversubscribed second-round financing that will help fund the development of its psychedelic therapies.

Along with psilocybin, the company is also working on an intranasal formulation of 5-MeO-DMT, a psychedelic compound found in plants and at least one species of toad, as a treatment for treatment-resistant depression (TRD).

Theravance has been forced to downsize its business after its lead pipeline drug ampreloxatine missed the mark in a phase 3 trial, cutting 75% of its workforce.

The Irish-American biopharma said this morning that ampreloxetine did not meet its objectives in a trial involving patients with symptomatic neurogenic orthostatic hypotension (nOH) – a rare condition in which the body loses its ability to regulate blood pressure properly.

Faced with the disappointment, Theravance has said it will shed 270 staff by the end of February, and switch its attention to respiratory disease pipeline. It will however complete a second phase 3 study of ampreloxatine in nOH, and a phase 2 trial of TD-1473 – a gut-selective JAK inhibitor – in ulcerative colitis.

The move is expected to slash costs by $165 million next year, which Theravance said would allow it to become cashflow-positive in the second half of 2022.

The company’s chief executive, Rick Winningham, said that the outcome of the ampreloxatine study was “not…what we had hoped to achieve,  especially given the clear unmet need for patients suffering from symptomatic nOH.”

Severely affected patients are unable to stand for more than a few seconds because of a decrease in blood pressure, according to the company.

Looking forward, Theravance’s respiratory portfolio is headed by Viatris-partnered Yulperi (revefenacin), a nebulised long-acting muscarinic antagonist (LAMA) for asthma and chronic obstructive pulmonary disease (COPD).

The drug has been approved in the US since 2019 but faces a very crowded market, although Theravance maintains that it could in time become a $400 million product, assuming ongoing studies aimed at extending its product label are successful.

Following after are wholly-owned lung-selective JAK inhibitors nezulcitinib (TD-0903) and TD-8236 which are in phase 2 trials for inflammatory lung diseases.

The company also has a royalty interest in GlaxoSmithKline’s triple therapy for COPD – Trelegy (fluticasone furoate/umeclidinium bromide/vilanterol) – which it says has the potential to become a $3 billion product. Trelegy made a little under $750 million in the first half of this year.

Shares in Theravance were down almost 39% in pre-market trading at the time of writing.

Alvotech, the Iceland-based biosimilar company, announced that the first patient has been dosed in the comparative, confirmatory efficacy and safety clinical study (AVT04-GL-301) for AVT04, Alvotech’s proposed biosimilar to the reference product Stelara®. The objective of the study is to demonstrate therapeutic equivalence between AVT04 and Stelara® in terms of safety, efficacy and immunogenicity in patients with moderate-to-severe chronic plaque psoriasis.

The AVT04-GL-301 study is being conducted in five countries in Central and Eastern Europe and it is expected that approximately 530 patients will be enrolled in the study.

In parallel, Alvotech is also conducting a PK similarity study (AVT04-GL-101) to demonstrate equivalent PK endpoints between the proposed biosimilar and the reference product Stelara. The AVT04-GL-101 study, that is also assessing safety and tolerability, is currently ongoing in Australia and New Zealand and is expected to enroll 294 healthy adult volunteers.

Ustekinumab, which is among the highest selling pharmaceutical products in the world, had worldwide sales of $7.7 bn in 2020.

AVT04 is the second proposed biosimilar product from Alvotech entering clinical studies, the first being AVT02, a proposed biosimilar to Humira®. Alvotech is the only known company that has both developed a biosimilar candidate for the high-concentration Humira® and is executing a switching study to support its approval as an interchangeable product.

Róbert Wessman, founder and Chairman of Alvotech commented, “As a founder, I am extremely proud to see us enter the second proposed biosimilar product into clinical trials. This brings us closer to our mission to expand patient access to high quality biosimilars at an affordable price.”

Mark Levick, CEO of Alvotech, added, “We are pleased to have reached this important milestone where the first subjects are being enrolled in clinical trials for AVT04, and we look forward to continuing with recruitment and patient follow-up.

“Additionally, the initiation of this clinical program, with two studies running in parallel, reinforces our commitment to improving the efficiency of the clinical development, with the ultimate goal of improving the lives of patients suffering from serious chronic or life-threatening diseases, through faster access to high-quality biosimilars.”

About Alvotech:

Alvotech is a multinational biopharmaceutical company focused on the development and manufacture of high quality biosimilars for global markets. We are specialists in biotechnology, seeking to be a global leader in the biosimilar space by delivering high quality, cost-competitive products and services to our partners and to patients worldwide. Our fully integrated approach, with high-quality in-house competencies throughout the value chain, enables the accelerated development of biosimilar products. Alvotech’s shareholder base includes, among others, Aztiq Pharma, led by founder and Chairman Mr. Robert Wessman, Fuji Pharma from Japan, YAS Holdings form Abu Dhabi, Shinhan from Korea, Baxter Healthcare SA from the US, ATHOS (Strüngmann Family Office) from Germany and CVC Capital Partners and Temasek from Singapore through their participation in Alvogen.