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The Technical Advisory Group of WHO, which met today, has recommended the Emergency Use Listing status for Bharat Biotech’s Covaxin – a decision that will ease international travel and the export of the indigenous vaccine. The World Health Organisation’s panel had last week sought additional clarifications from the Hyderabad-based pharma firm. Covaxin is a whole virion-inactivated vaccine against SARS-CoV2, developed in partnership with ICMR and NIV, Pune.

“WHO has granted emergency use listing (EUL) to #COVAXIN® (developed by Bharat Biotech), adding to a growing portfolio of vaccines validated by WHO for the prevention of Covid-19,” the UN health body said in a tweet.

Dr Krishna Ella, Chairman and Managing Director, Bharat Biotech, termed it a ‘significant step’. “The EUL authorisation for Covaxin will enable us to contribute to accelerating the equitable access of Covid-19 vaccine, and the access to our vaccine globally thereby addressing the current public health emergency,” a company statement quoted him as saying.

Shares of Inovio are down about 2% in premarket trading after reports surfaced of the cancellation of a six-year-old development agreement for a DNA cancer vaccine collaboration related to human papillomavirus with AstraZeneca.

In a U.S. Securities and Exchange filing, Inovio announced the Medimmune Limited, an AstraZeneca business, terminated the development program for INO-3112, a vaccine candidate that became known as MEDI0457. The agreement was first struck in 2015. In the filing, Inovio said the collaboration was terminated in its entirety.

When the two biotechs first struck the deal in 2015, Medimmune gained the rights to INO-3112, designed to target cancers caused by human papillomavirus types 16 and 18. With the deal scrapped, Inovio regains the rights to INO-3112. The Pennsylvania-based company is no longer eligible for any milestone payments or potential royalties from AstraZeneca’s development.

While that particular collaboration was scrapped, Inovio noted in its SEC filing that the companies are both still eligible to develop the asset in other indications. AstraZeneca is currently assessing MEDI0457 in patients with head and neck squamous cell carcinomas (HNSCC). The study is expected to be completed by the end of 2022.

While that deal has been terminated, Inovio has made headway in the ongoing battle against COVID-19 and other infectious diseases. In October, Inovio announced it completed enrollment for its Phase Ib Lassa fever vaccine candidate, INO-4500. The study is taking place in Africa, where Lassa has become endemic in certain regions. The study will include 220 participants.

Lassa fever is an animal-borne, hemorrhagic viral illness that has primarily been observed in parts of West Africa, including Ghana, where the study is taking place. Infection spreads through contact with infected rodents, as well as person-to-person transmission. The Coalition for Epidemic Preparedness Innovations (CEPI) supports the Lassa study. In addition to the Lassa vaccine, the CEPI funding also supports the development of a vaccine candidate for the Middle East Respiratory Syndrome (MERS).

In COVID-19, Inovio has advanced its vaccine candidate into Phase III studies. INO-4800, INOVIO’s DNA vaccine candidate, is composed of a precisely designed DNA plasmid that is injected intradermally. That is followed by electroporation using a proprietary smart device, which delivers the DNA plasmid directly into cells in the body, the company said. The approach is intended to produce a well-tolerated immune response.

The World Health Organization (WHO) supports the Phase III trial, conducted in Columbia, the Philippines, and Mali. The Phase III study will evaluate the efficacy of INO-4800 in a two-dose regimen, administered one month apart. The primary endpoint is the suppression of virologically confirmed COVID-19.

Phase II data posted in May found INO-4800 was well-tolerated provided “broad cross-reactive immune responses, including neutralizing antibodies and robust T cell responses, against variants of concern (alpha, beta, gamma and, in subsequent research, delta)—factors that could be critical in containing COVID-19 as it shifts from pandemic to endemic spread,” the company reported.

Roche’s Genentech unit has won FDA approval for Susvimo, an implant for eyesight-robbing disease wet age-related macular degeneration (AMD) that gives patients an alternative to regular injections into the eye.

Susvimo has the same active ingredient as Roche’s big-selling therapy Lucentis (ranibizumab), a VEGF inhibitor administered once a month that has been approved by the FDA since 2006 for wet AMD.

The port delivery system (PDS) implant is about the size of a grain of rice, is refillable and delivers the drug continuously for at least six months, so patients can manage wet AMD with just two treatments a year.

The FDA has approved Susvimo for the treatment of people with wet AMD who have previously responded to at least two anti-VEGF drugs such as Lucentis or Bayer and Regeneron’s rival Eylea (aflibercept).

The green light comes on the back of the phase 3 ARCHWAY trial which showed that Susvimo was equivalent to monthly Lucentis injections at maintaining vision in patients over 40 weeks, with 98% of patients lasting six months before needing a refill.

Additional Lucentis injections can be administered on top of Susvimo if needed, but just 1.6% of patients in the clinical trial needed the additional dosing.

In general, the implant was better tolerated than the regular Lucentis injections, although it was associated with a three-fold higher rate of endophthalmitis, an inflammation of the intraocular fluids.

In the 418-patient trial there were four cases, one of which resulted in permanent, severe vision loss, while the other three were treated and vision was restored to the level it was before implantation.

In a patient-reported outcome (PRO) survey, Susvimo recipients reported a strong preference for the implant over intraocular injections.

Roche said Susvimo would be priced at $9,250 for the first six months, with refills set at $8,000, which compares with a list price of around $1,230 for a monthly dose of Lucentis.

Cheaper biosimilar versions of Lucentis from Samsung Bioepis/Biogen, Hospira and Formycon/Bioeq are however due to enter the US market shortly.

Roche and Novartis share rights to Lucentis, with Roche selling the drug in the US and Novartis selling it in Europe and other markets.

Last year, Roche booked around $1.5 billion in US sales, while Novartis’ sales of the drug topped $1.9 billion, although the market leader remains Eylea which made more than $8 billion – thanks in part to more flexible dosing.

Roche and Novartis have gone in different directions as they prepare to defend their wet AMD franchises.  While Roche has placed its faith in Susvimo, Novartis focused on the development of a longer-acting VEGF antibody – Beovu (brolucizumab) – which is dosed every two or three months.

Beovu has struggled to gather momentum since its launch because of concerns about its safety, with second quarter sales only reaching $47 million.

The jury is also out on the prospects with Susvimo, with some analysts concerned that the endophthalmitis issue may hinder early take-up, making it hard to displace Eylea from its current dominant position – particular as cut-price biosimilars to Bayer and Regeneron’s drug are due in the US in 2023.

Roche has another iron in the wet AMD fire however with faricimab, a bispecific antibody targeting both VEGF and Ang-2 that only needs to be injected every four months and has shown impressive efficacy in clinical trials. The FDA started a priority review of the drug in July.

Eli Lilly has followed through on its plan to file for approval of its Alzheimer’s disease candidate donanemab, and is planning to take on Biogen and Eisai with a head-to-head trial against their recently-approved Aduhelm drug.

Lilly has also picked up an accelerated review for donanemab from the FDA, which is assessing the drug under a rolling license application that will see data submitted to the agency as it becomes available.

It could result in a conditional approval – based on the phase 2 TRAILBLAZER-ALZstudy – in the second half of next year if all goes to plan for Lilly.

The drugmaker isn’t however expecting sales to gather much momentum even if donanemab is approved, at least until the data from the confirmatory phase 3 study TRAILBLAZER-ALZ 2 comes in, currently due in 2023.

That has certainly been the case for Aduhelm (aducanumab), which brought in just $300,000 in sales in the third quarter and according to Biogen will remain “minimal” until a Medicare reimbursement review concludes, with a verdict expected early in 2022.

Lilly is seeking approval for donanemab in early-stage Alzheimer’s, and is hoping to get a speedy FDA green light on the back of amyloid clearance data as a surrogate marker for clinical efficacy, which is controversial as it does not reliably track with cognitive improvements in Alzheimer’s trials.

The impact of donanemab on cognitive decline was hard to interpret from the phase 2 trial, as benefits did not seem to correlate with amyloid plaque reduction using an initial statistical analysis, although Lilly crunched the numbers with a second model and said it had found an association.

The drugmaker has been emboldened to file early as a result of the controversial Aduhelm approval, which is seen as opening the door to swift FDA reviews for new Alzheimer’s therapies and conditional approvals ahead of pivotal trial readouts.

Biogen and Eisai’s confirmatory trial isn’t expected to generate results for several years, so Lilly has an opportunity to leapfrog Aduhelm if its phase 3 study is positive.

Added to that, the drugmaker is also planning a comparative study – TRAILBLAZER-ALZ 4 – that will pit donanemab directly against Aduhelm on their ability to clear amyloid plaques from the brains of patients with early symptomatic Alzheimer’s.

Results from that study could be available in the second half of next year, although it still doesn’t address the debate about the validity of amyloid clearance as a surrogate marker for clinical efficacy.

There was bad news for Lilly elsewhere is its Alzheimer’s pipeline as it announced the demise of anti-tau protein antibody zagotenemab, which had reached phase 2 but failed to have an impact on its primary endpoint.

Cortexyme trial disappoints

Elsewhere, a non-amyloid approach to treating Alzheimer’s pioneered by US biotech Cortexyme has suffered a setback after missing its objectives in a late-stage trial.

The company’s drug atuzaginstat targets a bacteria called Porphyromonas gingivalis, usually found in the mouths of people with periodontal disease, that has been associated with an increased risk of Alzheimer’s in some studies.

The phase 2/3 GAIN study in 643 patients showed no impact of the drug on scales used to monitor cognition in Alzheimer’s patents overall, although Cortexyme maintains there was a “clinically significant” benefit in a subgroup of 242 patients with P. gingivalis detectable in their saliva at the start of the trial.

The biotech said the data could allow it to design further studies that will enrol patients most likely to benefit from atuzaginstat, and is working on “next steps to advance this breakthrough treatment for the benefit of patients and their families.”

Malvern, Pa.-based Ocugen has submitted an Investigational New Drug (IND) to the U.S. Food and Drug Administration (FDA) to run a Phase III trial of India’s BBV152 (Covaxin), a vaccine against COVID-19.

Part of the trial’s goal is to determine if the vaccine’s immune response in a completed Phase III trial in India would be similar to the response in unvaccinated patients in the U.S. or those who have already received two doses of an mRNA vaccine.

Covaxin is a whole-virion inactivated COVID-19 product. That means they take the SARS-CoV-2 virus, kill it, and use it as the vaccine. The possible advantage over other vaccines is it creates a broader immunity against the virus, not just the virus’s spike protein, or parts of the spike protein, as most other vaccines do. Covaxin would theoretically have similar efficacy against all variants, although it doesn’t seem to in trials.

The vaccine was jointly developed by India’s Bharat Biotech and the Indian Council of Medical Research (ICMR). Ocugen has a deal with Bharat to develop the vaccine in the U.S. and Canada. It has been distributed under emergency use authorizations in 17 countries.

The vaccine received emergency authorization in India on January 3, 2021. However, there has been a long delay in authorization by the World Health Organization (WHO). This week, it got delayed once again as the WHO asked for additional information and clarifications from Bharat Biotech. The WHO expects to meet again for a final evaluation on November 3, if it receives the data.

Although the WHO approval isn’t necessary for use in India or the U.S., it is necessary for the vaccine to be recognized by foreign countries. It allows for fewer problems for vaccinated people in terms of international travel. WHO’s Emergency use listing (EUL) would mean the vaccine was eligible for global distribution to low- and middle-income countries under COVAX.

Shankar Musunuri, Ph.D., chairman, chief executive officer, and co-founder of Ocugen, said of the FDA application, “We are very excited to take this next step in the development of Covaxin, which we hope will bring us closer to introducing a different type of COVID-19 vaccine to the American public. We are hopeful that the study conducted under the IND, if allowed to proceed, will help demonstrate that the data from India will be applicable to the U.S. population.”

The Phase III immuno-bridging study, if given the green light, would enroll several hundred healthy U.S. adults. The participants would be given either two doses of Covaxin or placebo, 28 days apart. The primary endpoint would compare blood samples from U.S. participants who received the vaccine with samples in the Phase III trial performed in India. A secondary endpoint is an immunogenic profile of the vaccine. It will also determine safety and tolerability in the U.S. population. Ocugen hopes to wrap up the study in the first half of 2022.

The Phase III trial in India performed by Bharat Biotech involved 25,798 participants who received the vaccine or placebo. The primary endpoint was the prevention of symptomatic COVID-19 within at least 14 days after the second dose.

Data from that trial reported 93.4% efficacy against severe COVID-19, 77.8% efficacy against symptomatic COVID-19, and 63.6% against asymptomatic disease. A sub-analysis of the data looked at its effectiveness against variants. The analysis showed that 90% of infections were associated with a variant, and 59% were the Delta variant. The vaccine demonstrated 65.2% efficacy against Delta.

An artificial intelligence-based tool for identifying hard-to-detect spinal fractures, developed by Belgian drugmaker UCB, has been licensed out to ImageBiopsy Lab for further development.

The digital health tool, known as BoneBot, applies machine learning to X-rays to detect ‘silent’ or asymptomatic fractures in the vertebrae of the spine, a feature of the bone-wasting disease osteoporosis that can remain undiagnosed in more than two-thirds of cases.

Catching these fractures more quickly could allow diagnosis and treatment earlier, and potentially reduce complications associated with osteoporosis.

According to UCB – which sells medicines to treat osteoporosis – licensing the technology out to ImageBiopsy will accelerate its development and could see it brought into clinical practice by 2023.

The AI will be integrated into ImageBiopsy’s existing AI-based platform for diagnosing musculoskeletal (MSK) disease from radiographs which includes modules for osteoarthritis, wrist bone fractures and early signs of osteoporosis.

BoneBot concentrates on vertebral compression fractures (VCFs), which affect nearly 700,000 people each year in the US, according to figures from the American Academy of Orthopaedic Surgeons (AAOS).

VCFs are the most common form of osteoporosis-related fracture and are associated with increased mortality, with an estimated 4.4-fold increase in the chance of dying, but are missed by radiologists in up to 50% of cases, according to a 2018 study.

The AI is used to identify tiny fractures on radiographs, as well as to distinguish them from other potential bone problems such as vertebral degeneration, which may be caused by ageing, arthritis and other conditions like infection or tumours.

“As digitalisation of health increases, so does the potential of leveraging AI for improving care for many diseases, including osteoporosis,” said Emmanuel Caeymaex, who heads UCB’s immunology and US business units.

“The number one risk factor for fragility fractures is a previous fracture,” he added. “Identifying and appropriately treating patients who have already suffered a vertebral fracture is therefore key to ensuring that patients can continue to live their life to the fullest and avoid further fracture.”

BoneBot has some rivals in the category, notably Zebra Medical Vision which recently won grant funding in the UK to accelerate the testing and evaluation of its AI-based system for detecting vertebral fractures.

Last year, Zebra secured a current procedural terminology (CPT) code for the AI for detection of VCF as an incidental finding in chest CT scans, which becomes effective on 1 January next year. The code will allow clinics to code for this AI application and help them identify more patients for potential osteoporotic fractures.

The FDA has approved an artificial intelligence-based test for early detection of dementia that can be carried out on an iPad in five minutes.

The CognICA Integrated Cognitive Assessment (ICA) test developed by London, UK-based company Cognetivity Neurosciences has been approved by the FDA as an alternative to traditional pen-and-paper tests with some key advantages, according to its developer.

Those include high sensitivity to detect early-stage cognitive impairment, which could allow early intervention with treatment or lifestyle changes that might help to slow down the progression of dementia.

The digital format also helps to avoid cultural or educational bias in testing, and helps to avoid scenarios where people tested on multiple occasions learn how to score better, masking increases in impairment, said Cognetivity.

It can also be carried out unsupervised, saving time and money for health systems and making it particularly suitable for assessments when access to care may be restricted, or to allow ongoing monitoring of patients without clinic visits.

The test displays images at a rapid pace on the iPad screen and asks users to identify them as either animal or non-animal.

That draws on humans’ strong intrinsic reaction to animal stimuli – sometimes referred to as the ‘food or fear’ response – and the ability of a healthy brain to process images of animals in less than 200 milliseconds.

The test targets brain areas that are affected in the initial stages of cognitive disorders before severe memory symptoms become apparent, according to Cognetivity.

CognICA has already been approved in Europe as a CE-marked medical device, and is being used in primary and specialist clinical care by NHS trusts in the UK, but the FDA approval opens up a big new market for the software.

Cognetivity’s chief executive Dr Sina Habibi said the company will now start to expand its presence in the US with the formation of regional offices to help spearhead the commercial rollout of CognICA, adding to its current locations at the Texas Medical Centre and Silicon Valley in California.

“The benefits of reaching this milestone will extend far beyond the US itself,” he said.  “This mark of certification will bolster our regulatory and commercial efforts in other international jurisdictions as we continue to pursue our ambitions for deployment on a truly global scale.”

There is a growing number of organisations turning to digital tools and AI to improve on the traditional pen-and-paper tests for detecting dementia.

Earlier this week, for example, Altoida partnered with drugmaker Eisai and Ionian University on a five-year clinical trial to see if its AI-based software can detect neurocognitive impairments that can’t be found using current tests.

Early detection is a key objective for Eisai, which along with Biogen brought the first potentially disease-modifying therapy for Alzheimer’s – amyloid-targeting antibody Aduhelm (aducanumab) – to the market in the US earlier this year.

We’ve analysed 10 years’ worth of clinical trials data from GlobalData to pick out key geographic trends.

The Asia-Pacific region has seen a 38% increase in the number of cardiovascular trials taking place over the past decade, the largest increase for any region worldwide.

The region now ranks first for the total number of trials taking place, compared to its third placed ranking in 2010.

These figures come from GlobalData’s extensive clinical trials database which seeks to track the number of clinical trials taking place in countries around the world, in numerous therapy areas.

Asia-Pacific

The Asia-Pacific region saw the biggest increase in cardiovascular related trials.

In 2020, the largest proportion of trials in the region took place in China with 60.6% of all trials in the region taking place there.

South Korea and India had the next largest percentage of trials taking place in the region with 8.4% and 7.6%, respectively.

Middle East

The Middle East saw a 33% increase in the number of cardiovascular trials taking place.

Iran saw the largest amount of trials taking place, in 2020, at 81.1%.

Trials in Israel and Saudi Arabia also made up a large proportion of the trials taking place with 14.4% and 3.8%, respectively.

Africa

Africa saw a 14% increase in the number trials taking place.

Egypt, South Africa and Tunisia made up the most trials in the region, with 81.8%, 6.1% and 3%, respectively.

Europe

Europe saw a 15% decrease in cardiovascular related trials taking place.

Russia saw the largest percentage of trials taking place in the region at 11.2%.

France and the United Kingdom also made up a significant proportion of the trials taking place.

North America

North America saw a decrease in the number of cardiovascular trials.

The region saw a 16% decrease in the number of trials.

The United States made up 72.8% the largest proportion of trials taking place in the region.

Canada and Mexico also made up a large amount of the trials taking place with 21.5% and 5.7%, respectively.

South and Central America

South and Central America saw the biggest decrease in cardiovascular trials.

The number of trials in the region fell by 42% between 2010 and 2020.

Brazil saw the largest percentage of trials taking place in the region with 57.1%.

The safety profile in the trial was consistent with already observed data from trials of sintilimab and Byvasda.

Innovent Biologics has reported that its sintilimab met the prespecified primary goal in the ORIENT-31 clinical trial in epidermal growth factor receptor (EGFR)-mutated nonsquamous non-small cell lung cancer (nsqNSCLC) patients.

Co-developed by Innovent in collaboration with Eli Lilly and Company, sintilimab is an immunoglobulin G4 monoclonal antibody.

The drug attaches to programmed cell death protein 1 (PD-1) molecules present on the T-cell surface and hinders the PD-1 / PD-Ligand 1 (PD-L1) pathway, reactivating T-cells to destroy cancer cells.

Approximately 480 individuals with EGFR-mutated locally advanced or metastatic nsqNSCLC who have progressed on receiving EGFR tyrosine kinase inhibitor (TKI) therapy will be part of the trial.Subjects were categorised into a 1:1:1 ratio to receive sintilimab plus Byvasda  and chemotherapy, sintilimab plus placebo two and chemotherapy, or placebo one, placebo two, and chemotherapy.

Progression-free survival (PFS) was the trial’s primary goal, while the secondary goals comprised overall survival (OS), investigator evaluated PFS, safety and objective response rate (ORR).

According to the latest interim analysis findings, sintilimab plus Byvasda and chemotherapy offered substantial improvement in PFS in trial subjects.

In the intent-to-treat population, it was found that sintilimab plus Byvasda and chemotherapy showed a significant and clinically meaningful improvement in PFS versus chemotherapy..

Sintilimab plus chemotherapy also demonstrated a trend of PFS benefit as against chemotherapy alone.

The safety profile of the trial was in line with those already reported from trials of sintilimab and Byvasda. No new safety signals were observed.

Innovent Biologics senior vice-president Dr Hui Zhou said: “Lung cancer has the highest mortality rate among all tumour types both in China and worldwide.

“In China, EGFR-mutated NSCLC accounts for 40% to 50% of nonsquamous NSCLC, and the treatment options for these patients after treatment with first, second and third-generation EGFR-TKIs are very limited, representing a large unmet medical need.

“Through the joint efforts of investigators, ORIENT-31 achieved these encouraging research results.”

In August this year, Innovent reported that its sintilimab plus chemotherapy met the predefined primary goal of Phase III ORIENT-16 trial as first-line therapy for unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

Valneva has reported that its inactivated, adjuvanted Covid-19 vaccine candidate, VLA2001, met the co-primary goals of the Phase III Cov-Compare clinical trial in adolescent and adult subjects.

VLA2001 comprises inactivated whole SARS-CoV-2 virus particles with high S-protein density, along with alum adjuvant and Dynavax Technologies’ CpG 1018 adjuvant.

The randomised, controlled, observer-blind, comparative immunogenicity Phase III trial enrolled 4,012 adults and is currently recruiting 660 adolescent subjects aged 12 years and above.

The trial is being carried out at 26 trial centres in the UK. A total of 2,972 subjects aged 30 years and above were categorised in a 2:1 ratio to receive two intramuscular doses of either VLA2001 or AstraZeneca’s Covid-19 vaccine, AZD1222 (ChAdOx1-S), at a gap of 28 days.

Valneva noted that the other co-primary goal is non-inferiority of seroconversion rates (SCR) of neutralising antibodies as assessed at two weeks on receiving the second shot in people aged 30 years and above.

The trial will also assess the safety and tolerability of the VLA2001 vaccine two weeks after the second dose in adult and adolescent subjects.

According to the data from adult subjects aged 18 years and above, the trial met its co-primary endpoints.

VLA2001 was superior to AZD1222 and showed non-inferiority of SCR at two weeks after the second shot in individuals aged 30 years and above.

VLA2001 elicited wide-ranging antigen-specific IFN-gamma inducing T-cells that are reactive against the S, N and M proteins in a subset of subjects.

The vaccine was demonstrated to be well tolerated with its tolerability profile more favourable than AstraZeneca’s shot.

Younger subjects receiving VLA2001 had an overall safety profile in line with the older age group.

The trial’s exploratory endpoint of incidence of Covid-19 cases was comparable across the treatment arms.

Furthermore, the absence of severe cases of Covid-19 could indicate that the vaccines used in the trial averted severe disease caused by the SARS-CoV-2 variants, especially the Delta variant.

Valneva CEO Thomas Lingelbach said: “These results confirm the advantages often associated with inactivated whole virus vaccines.

Valneva initiated the Phase III VLA2001-304 trial of its VLA2001 in New Zealand this August.