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Alphabet subsidiary Verily has signed an agreement to acquire a clinical trial management system (CTMS) developer SignalPath to strengthen its clinical research capabilities.

Established in 2014, SignalPath designed its CTMS platform to enhance the ease, quality and efficacy with which clinical research is carried out at trial sites.

The CTMS also reduces fragmentation by using a modern software architecture and a Cloud-based platform to help a trial site manage its clinical trials portfolio.

The deal with Verily will enable SignalPath to offer clinical research sites with access to an emerging portfolio of resources, tools and trial opportunities.

 

SignalPath co-founder and CEO Brad Hirsch said: “Combining these capabilities with Verily’s clinical studies platforms business accelerates our ability to scale these solutions and make them available to a larger group of sites, as well as provide entirely new opportunities to our network.”

Verily expects the acquisition to boost its current clinical trial system and evidence generation platform called Baseline.

Baseline allows improved and quicker trial execution, enhanced data aggregation and analysis, as well as flexible options for decentralised and hybrid trials.

The platform also enables the capture of real-world data, including data from new sensors and biomarkers.

The Baseline community currently includes more than 500,000 people with an interest to be part of clinical research. These individuals are automatically linked with research opportunities based on their interests and profiles.

Verily Clinical Studies Platforms president Amy Abernethy said: “Joining forces helps to accelerate and scale our shared vision, increase efficiency and lower costs in clinical trials, empower clinical research sites with world-class technology, and ultimately bring medicines to patients faster.”

At the closing of the acquisition, SignalPath employees will become part of Verily’s clinical research business and remain in Raleigh, North Carolina, US, expanding the latter’s geographic presence.

In May 2019, Verily formed a strategic alliance with Novartis, Pfizer, Otsuka and Sanofi to transform clinical research.

Labcorp and Community Clinical Oncology Research Network (CCORN) have partnered to gain improved insights into the effect of disparities in precision medicine for cancer.

The companies expect that data from a patient registry and biobank can aid in designing oncology clinical trials in diverse patient populations in the future.

Patient registries are observational studies that gather standardised information on a group of patients with the same condition or experience.

 

As part of the collaboration, the PREFER patient registry will enrol up to 2,500 advanced solid tumour cancer patients at several sites in the US starting next month.

This registry is set to offer important insights from clinical and lab data about the unmet needs among cancer patients from diverse populations.

Labcorp and CCORN will use a genomic and immune-profiling, tissue-based test called OmniSeq INSIGHTsm, which leverages next-generation sequencing technology, to detect the incidence of actionable biomarkers and driver mutations exclusive to various ethnicities.

The companies will also develop a biobank to provide access to real-world evidence and recognise the source of disparities.

The patient registry and biobank information could help enhance the design of cancer trials, aid patient enrolment and promote the growth of genomic profiling testing in diverse populations, Labcorp said.

CCORN founder and chairman Dr Kashyap Patel said: “Drug development processes have been relatively unsuccessful in reflecting demographic diversity in clinical trials, which further contributes to disparities in care and outcomes for those groups.

“It’s imperative that we determine how and why disparities occur, and this collaboration with Labcorp will be a major step in this regard.”

According to a 2020 report by American Association for Cancer Research, 34% of cancer-related deaths could be avoided in adults aged 25 to 74 years in the US if disparities in trial participation were addressed.

In March this year, Labcorp extended its alliance with PathAI to enable the deployment of the latter’s algorithms in prospective trials of cancer and other diseases.

When the first vaccine was authorized in December, it felt like a light at the end of a long, dark, pandemic tunnel. The mRNA vaccines, in particular, showed high efficacy rates at preventing severe illness from SARS-CoV-2. Yet scientists issued a warning – vaccination may not guarantee to stop the transmission. 

Today their fears are being realized as the Delta variant, in particular, proves its ability to spread through vaccinated people. That’s because while the current authorized intramuscular injected vaccines are champs at eliciting an immune response to prevent severe disease, they do not generate “sterilizing immunity, protection in the nasal passages to block all infection.

In steps Indian vaccine maker Bharat Biotech already has a two-dose, injectable COVID-19 vaccine, Covaxin, authorized in India for ages 12 and up. Now the company is moving forward with its second vaccine against the novel coronavirus with a different mode of administration. 

Bharat’s intranasal vaccine is the first to receive regulatory approval to move on into Phase II/III trials. In a Phase I trial in age groups from 18-60, BBV154 was well-tolerated, safe and immunogenic, while eliciting high levels of neutralizing antibodies in animal studies.

Many believe this path of vaccination, particularly in combination with the existing intramuscular vaccines, could be a game-changer. By administering a vaccine directly into the nasal cavity, the mucus membranes of the nose and throat would provide better protection than the intramuscular alone. 

A Bharat staffer, Dr. Raches Ella, tweeted back in July that this intranasal vaccine approach “may overcome the shortfalls of intramuscular vaccines… If achieved, we may limit transmission.”

Bharat is calling all hands on deck, hoping to work a combination of its already authorized Covaxin injection, followed by its nasal vaccine. 

Chairman and managing director Dr. Krishna Ella summarized the approach saying, “so that Covaxin primes the system of innate immunity and then the boost by the nasal which produces three immune responses — the IGG, the IGA and then mucosal immunity, all three of which are powerful and can protect a person from getting infected.”

According to the Serum Institute of India, a booster dose would provide a four-fold increase in neutralizing antibody levels.

An intranasal vaccine has additional advantages too. It can be administered by staff with minimal training. It’s more acceptable for those with fear of needles and potentially children. Even the amounts of medical waste produced would be less than what’s piled up from the injected vaccines. 

Bharat isn’t alone in its belief that an intranasal COVID-19 vaccine is the next step to stopping the global pandemic. Maryland-based Altimmune had also been working on a candidate. But in June, the company announced it was discontinuing its development due to “disappointing results.” AdCOVID fell short of expectations after immunogenicity data exhibited very low immune responses in every parameter where it was tested.  

Experts are hoping nasal vaccinations, in combination with an intramuscular injection, could be a “gamechanger” in the battle against COVID-19.

The World Health Organization (WHO) has launched the new phase of its Solidarity clinical trial to assess three new drugs to treat patients hospitalised with Covid-19.

Named Solidarity PLUS, the new trial will investigate artesunate, imatinib and infliximab, which are already used to treat other diseases.

An independent expert panel chose these drugs as they exhibited the potential to lower the mortality risk in hospitalised patients with Covid-19.

Said to be the largest worldwide partnership between WHO member states, the trial can evaluate several therapies simultaneously under one protocol.

Over the duration of the trial, new therapies can be added and ineffective therapies can be removed.

Artesunate, imatinib and infliximab are manufactured by Ipca, Novartis and Johnson & Johnson, respectively. The companies donated the drugs for use in Solidarity PLUS.

An artemisinin derivative, artesunate is used for malaria treatment while imatinib is a small molecule tyrosine kinase inhibitor meant to treat some cancers.

Meanwhile, infliximab is a tumour necrosis factor (TNF) alpha inhibitor that is indicated for the treatment of immune system-related diseases such as Crohn’s disease and rheumatoid arthritis.

Participants in the Solidarity PLUS trial will receive intravenous artesunate for seven days, oral imatinib once a day for 14 days or intravenous infliximab as a single dose.

WHO director-general Dr Tedros Adhanom Ghebreyesus said: “Finding more effective and accessible therapeutics for Covid-19 patients remains a critical need, and WHO is proud to lead this global effort.

“I would like to thank the participating governments, pharmaceutical companies, hospitals, clinicians and patients, who have come together to do this in true global solidarity.”

The first Solidarity trial tested remdesivir, hydroxychloroquine, lopinavir and interferon. These drugs demonstrated little or no effect on hospitalised Covid-19 patients, WHO noted.

Covid-19 lockdowns and social distancing measures have caused significant disruptions to clinical trials and accelerated the use of virtual trials. Companies that had not considered this model before have had no option but to rapidly implement new technologies and procedures to maintain business continuity. Over the past 18 months, many sponsors have enhanced their virtual trial capabilities, while many leading clinical research organisations (CROs) have expanded their services in response to growing demand for these services.

In line with increased demand for alternatives to traditional trials during the pandemic, the number of jobs related to virtual trials has increased over the past 18 months. Using a range of keywords related to virtual trials, an analysis of GlobalData’s Job Analytics Database found around 1,000 jobs from pharmaceutical companies or CROs from July 2019 to July 2021. Data show an increase from 30 posted jobs in the third quarter of 2019 to 160 posted jobs in the same quarter of last year, with further increases to more than 200 posted jobs in the first two quarters of this year (Figure 1).

Depending on the main keywords used in the title or description of a job posting, jobs were grouped into ‘Decentralised/Virtual/Remote/Siteless/Hybrid’ or ‘eCOA/ePRO/eConsent/eDiary’. In total, posted jobs mentioning just e-clinical technologies, such as eCOA or ePRO, were more common (78%) than those mentioning terms such as ‘virtual’ or ‘decentralised’ (22%). Despite this, the number of posted jobs containing terms such as ‘virtual’ or ‘decentralised’ rose last year, increasing from 12 in the first quarter of the year to around 60 in the first two quarters of this year, likely as a result of the Covid-19 pandemic and the need to transition trials to fully virtual models.

More than 60% of the jobs found between July 2019 and July 2021 were posted by pharmaceutical companies. CROs such as PRA Health Sciences, Parexel and PPD posted a higher proportion of jobs containing terms such as ‘virtual’ or ‘decentralised’. PRA Health Sciences posted more than 200 related jobs since July 2019, with the majority seen over the past 12 months. Bristol-Myers Squibb and AstraZeneca are leading pharmaceutical companies in terms of job postings in this space.

This increased use of virtual trials will lead to increased demand for expertise in areas such as wearables, remote monitoring devices and analysis of electronically collected data. One potential barrier to hiring in the virtual trial field, however, is a shortage of skills. Attracting qualified and experienced workers to deploy Internet of Things (IoT) solutions and analyse resulting datasets in healthcare is a major issue for the healthcare ecosystem and is expected to constrain market growth. For example, in GlobalData’s State of the Biopharmaceutical Industry 2021 report, a lack of specific skills and talents was chosen by the highest proportion of respondents as the main barrier to digital transformation initiatives for organisations. The industry requires skills in digital, advanced data analytics, artificial intelligence and machine learning, as well as a flexible and educated workforce.

At present, many pharmaceutical companies and sponsors are not fully ready to utilise the data generated by connected medical devices. Recruiting top digital talent is a priority across IoT and connected devices and will be essential for the validation and utilisation of remote technologies in clinical trials.

The Drugs Controller General of India has granted restricted emergency use authorisation to Moderna for its Covid-19 vaccine. It has also allowed Cipla to import donated doses of vaccine.

US vaccine manufacturing giant Moderna has secured restricted emergency use authorisation for its Covid-19 vaccine in India. The approval was granted by the Drug Controller General of India (DCGI), the government said on Tuesday.

Besides this, Indian drug manufacturer Cipla has been given permission to import Moderna’s Covid-19 vaccine. However, at present, Cipla is allowed to import only those doses that Moderna has committed to donate to India.

Following today’s developments, Moderna has become the fourth Covid-19 vaccine that will be used in India’s vaccination drive. The vaccines that India is currently using are:

• Covishield: It was developed by the Oxford University and AstraZeneca and is manufactured in India by the Pune-based Serum Institute of India.
• Covaxin: It was developed and manufactured by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR).
• Sputnik V: It was developed and manufactured by Gamaleya Research Institute of Epidemiology and Microbiology in Russia.

“An application was received from Moderna through their Indian partner Cipla following which Moderna’s Covid-19 vaccine has been granted restricted emergency use authorisation by the drug regulator. This new permission for restricted emergency use potentially opens up a clear possibility of this vaccine being imported to India in the near future,” NITI Aayog Member (Health) Dr VK Paul said.

Dr Paul added that the government’s is continuing with its efforts to invite and to have other internationally developed vaccines, specifically Pfizer and J&J.

“Those processes are on. We are also looking at increasing the production of availability of vaccines that are being manufactured in our country.”

Besides seeking regulatory approval in India, Moderna has also informed that the US government has agreed to donate a certain number of doses of the Moderna Covid-19 vaccine through COVAX to India use and has sought approval from the Central Drugs Standard Control Organisation (CDSCO) for these vaccines.

It is these donated doses of the Moderna vaccines that Cipla will be currently importing.

“I want to thank the government of India for this authorisation, which marks an important step forward in the global fight against the pandemic,” said Stéphane Bancel, Chief Executive Officer of Moderna. “We are committed to making our Covid-19 vaccine available around the world.”

Cipla filed its application to import and market Moderna’s Covid-19 vaccine on Monday. In its application, Cipla referred to DCGI notices dated April 15 and June 1, which state that if a vaccine is approved by the USFDA for EUA, it can be granted marketing authorisation in India without bridging trial.

The most complete database of protein structures ever assembled, developed with the help of Google’s artificial intelligence unit DeepMind, has been made freely available to researchers around the world.

DeepMind partnered with the European Molecular Biology Laboratory (EMBL) to come up with the AlphaFold database, which predicts the three-dimensional structures of the human proteome – nearly all (98.5%) of the 20,000 or so proteins expressed by the human genome.

AlphaFold has doubled the number of protein structures known to research, and that could help accelerate research into how diseases affect the body, and develop new medicines that can latch on to problem proteins effectively.

It is one of the most significant contributions that AI has made to the advancement of science, according to its developers, although they acknowledge that some of the predictions will still need to be validated in experimental testing. Around a third of the structures are considered to be detailed and precise enough to allow drug design.

The team has also used the AI to model hundreds of thousands of proteins from other species, including 20 model organisms used in research like the mouse, nematode worm and fruit fly, and human pathogens like the malaria parasite.

DeepMind‘s founder and chief executive Demis Hassabis said that AlphaFold solves one of the biggest problems in biology, namely what shape a protein take in the body, and if that can be predicted simply from the amino acid sequence of the gene coding for it.

He said the database has applications in understanding the fundamental mechanisms of life, drug design, and other applications like creating designer proteins with different functions. The source code behind the latest version of AlphaFold was released a few days before the paper describing the proteome database was published.

“Our goal at DeepMind has always been to build AI and then use it as a tool to help accelerate the pace of scientific discovery itself, thereby advancing our understanding of the world around us,” he said.

“In the coming months we plan to vastly expand the coverage to almost every sequenced protein known to science – over 100 million structures,” he added.

The decision to make the database freely available is to make sure that AlphaFold has the greatest scientific and societal impact possible, according to Hassabis.

AlphaFold is already being used by early partners researching neglected diseases, studying antibiotic resistance, recycling single-use plastics, and understanding the biology of the COVID-19 virus SARS-CoV-2.

EMBL director general Edith Heard said that AlphaFold “was trained using data from public resources built by the scientific community so it makes sense for its predictions to be public.”

She added: “I believe that AlphaFold is truly a revolution for the life sciences, just as genomics was several decades ago.”

Since the outbreak of Covid-19 worldwide, scientists and pharmaceutical companies alike have raced to find ways to protect against and treat the virus. One method of administration increasingly being pursued is the nasal spray; the cells lining the nose have been identified as a key entry point for the novel coronavirus, and a spray mechanism could circumvent the obstacles associated with other forms of treatment, such as injection or oral routes.

Pharmaceutical Technology takes a look at some of the Covid-19 nasal sprays currently in development.

COVIXYL-V (Salvacion USA)

New Jersey-based medical devices company Salvacion, in partnership with the National Cancer Institute, is developing a nasal spray technology to prevent Covid-19 infection. The spray, COVIXYL-V, contains the active ingredient ethyl lauroyl arginate hydrochloride (ELAH) and creates a physical barrier that prevents the virus from attaching itself to the surface in the nasopharynx.

Salvacion has submitted COVIXYL-V to the FDA for pre-emergency use authorisation and is awaiting approval for the product’s commercial use in the US.

Nasitrol (Amcyte Pharma)

Nasitrol, an algae-derived nasal spray developed by Argentinian company Laboratorio Pablo Cassara, has been approved in Argentina for the prevention of the common cold for a decade. Now, the product is showing promise to prevent the transmission of Covid-19.

A recent study, conducted at eight hospital intensive care units (ICUs), administered either Nasitrol or placebo to a sample of 394 clinically healthy physicians, nurses and other medical professionals who provided care to coronavirus patients and who had not yet been vaccinated against the disease.

The incidence of Covid-19 infection was significantly lower in the Nasitrol group compared with placebo, at 1% versus 5%. There were no differences in the incidence of adverse events between the two groups.

Nasitrol will be marketed by Amcyte in the US through a licensing agreement with Laboratorio Pablo Cassara.

IGM-6268 (IGM Biosciences)

IGM-6268 is an intranasally-administered immunoglobulin M (IgM) antibody treatment candidate for the treatment and prevention of Covid-19.

In preclinical studies, IGM-6268 demonstrated significantly greater neutralisation of SARS-CoV-2 with an IgM antibody compared to immunoglobulin G antibodies, the potent neutralisation of all evaluated mutant variants of concern and variants of interest, and the ability to provide effective preventative and therapeutic protection when delivered intranasally in mice.

American clinical-stage biotech IGM Biosciences has exclusively licensed the rights to the antibodies used to generate IGM-6268 and related intellectual property from the University of Texas System.

Carragelose (Marinomed Biotech)

Marinomed Biotech’s red seaweed-derived Carragelose is a broadly active antiviral compound for treating respiratory diseases, approved in the EU, Australia and parts of Asia in the form of nasal sprays, throat sprays and lozenges.

Carragelose coats the mucosal tissues of the respiratory tract, forming a physical barrier that helps to protect against viral infection.

According to a trial conducted by an Argentinian research group, a Carragelose-based nasal spray showed significant efficacy in the prevention of Covid-19 among hospital staff managing patients with the virus.

The percentage of participants that developed Covid-19 was significantly lower in the group that received the iota-carrageenan spray compared to placebo – 1% and 5.1%, respectively.

Enovid (SaNOtize)

Canadian biotech SaNOtize’s nitric oxide nasal spray Enovid became available in pharmacies in Israel earlier this month as a treatment for Covid-19.

The spray received emergency use authorisation in Israel in early July after Phase II trials showed it reduces SARS-CoV-2 viral load, and therefore decrease a person’s transmission of the virus.

Releasing a small dose of nitric oxide, a natural nanomolecule with anti-microbial properties including against SARS-CoV-2, Enovid provides a physical and chemical barrier in the nose.

In June, SaNOtize announced it had received approval from Health Canada to proceed with enrolment of volunteers in Phase III trials, and submitted an application for a New Drug Submission under Health Canada’s Interim Order.

The company is in the process of regulatory submissions in several other countries, including India, Brazil and Mexico.

Digital devices enable the measuring of biomarkers such as heart rate, blood sugar and even sleep that can help in assessing the health of a patient.

Digital biomarkers measured by wearables, sensors and other digital devices are increasingly playing a key role in the healthcare sector by enabling remote monitoring of diseases and even clinical trial patients.

Verdict has conducted a poll to assess which of the markers measured by digital health technologies have the most potential for use in clinical trials. Respondents were allowed to choose from one of the five markers namely heart rate, respiration patterns/rate, physical activity, medication adherence, and sleep.

Analysis of the poll responses shows that heart rate and respiration patterns/rate have the most potential for immediate use in clinical trials, according to 29% and 24% of the respondents, respectively.