gr-cis.com

The US Government’s Biomedical Advanced Research and Development Authority (BARDA) has made an initial investment of approximately $55 million for rapid development of VIR-2482, the Vir Biotechnology’s investigational prophylactic monoclonal antibody (mAb) for seasonal and pandemic influenza viruses.

Its purpose being to support pandemic preparedness for influenza and other infectious disease threats, this is the first award from BARDA – part of the US Department of Health and Human Services’ (HHS) Administration for Strategic Preparedness and Response (ASPR) – for pre-exposure prophylaxis for influenza.

VIR-2482 is an investigational intramuscularly administered influenza A-neutralising mAb. It has been shown in vitro to cover all major influenza A strains that have arisen since the 1918 ‘Spanish flu’ pandemic and is designed as a universal prophylactic for influenza A.

Furthermore, VIR-2482 could have the potential to overcome the limitations of current flu vaccines and result in higher levels of protection, given it does not rely on an individual to create their own protective antibody response. Additionally, the incorporated Xencor Xtend Technology is half-life engineered, meaning a single dose could potentially last an entire flu season.

Seasonal influenza (or flu) is a highly contagious respiratory disease that can cause severe illness and life-threatening complications. In just the past few years, seasonal influenza has resulted in around 4 million hospitalisations and circa 500,000 global annual deaths.

Pandemic influenza, by contrast, is a contagious airborne respiratory disease with unpredictable timing and severity and against which humans have little or no immunity. Four such pandemic influenzas have occurred in only the past century, with the 1918 ‘Spanish flu’ alone having resulted in 50 million deaths worldwide.

Given the past two years’ and ongoing experience with SARS-CoV-2 and its variants, the BARDA multi-year contract – potentially an investment of up to $1 billion in total – aims to continue the Authority’s efforts in preparing for and responding to public health emergencies. Currently, there is a significant unmet need to address shortcomings in preventative and therapeutic options for influenza, the efficacy of the present options that do exist ranging from only 10% to 60%.

Therefore, this initial $55 million investment aims to address these shortcomings. It includes for a phase 2 pre-exposure prophylaxis trial, to begin this second half of the year, with initial data expected by mid-2023. The balance of the award is subject to up to 12 options being exercised by BARDA in further support of the development of pre-exposure prophylactic antibodies, including and beyond VIR-2482.

This extended area, beyond prevention of influenza illness, will potentially be for supportive medical countermeasures for up to 10 “other pathogens of pandemic potential”, whether they be “chemical, biological, radiological [or] nuclear”.

Dr Rajesh Gupta, vice president, global health portfolio and public-private partnerships at Vir Biotechnology, said: “COVID-19 reinforced the ever-present global threat of infectious diseases, and the critical need for readily available solutions in advance of the next pandemic.”

A commercial-stage immunology company, Vir Biotechnology’s current development pipeline includes product candidates targeting hepatitis B and hepatitis D viruses and human immunodeficiency virus, in addition to influenza A and COVID-19, the latter of which Vir (together with GSK) previously delivered the antibody sotrovimab (Xevudy) for. The company also co-discovered ansuvimab-zykl for addressing the Ebola crisis.

Bolyn Hubby, PhD, executive vice president and chief corporate affairs officer at Vir Biotechnology, said: “Just as the COVID-19 pandemic required unprecedented cross-sector collaboration around the globe, tackling the outbreaks and pandemics of tomorrow will require an ‘all hands on deck’ approach that unites a broad array of public and private organisations.”

Under a collaboration agreement signed with GlaxoSmithKline (GSK) in 2021, GSK holds an exclusive option to lead post-phase 2 development and commercialisation of VIR-2482.

The trial will evaluate the variation in the immune microenvironment within tumours, as well as in the peripheral blood.

Citius Pharmaceuticals has entered a clinical partnership with the University of Pittsburgh for a Phase I/Ib trial of I/ONTAK (denileukin diftitox or E7777) plus pembrolizumab to treat recurrent or metastatic solid tumours.

The open-label, investigator-initiated trial will assess T-reg cell depletion on administering I/ONTAK along with pembrolizumab in such patients. 

It will have two parts. The Part I dose escalation trial will have four cohorts assessing three, six, nine, and 12mcg doses of I/ONTAK and will enrol 18-30 subjects. 

The Part II dose expansion trial will enrol nearly 40 subjects to assess the safety and tolerability of the recommended combination dosage of I/ONTAK plus pembrolizumab. 

The trial will also evaluate the variation in the immune microenvironment within tumours, as well as in the peripheral blood. 

Objective response (complete response plus partial response), overall survival, and progression-free survival will be the trial’s secondary endpoints.

The University of Pittsburgh trial is anticipated to commence in the fourth quarter of this year.

The company is also partnering with a Phase I investigator-initiated trial at the University of Minnesota (UMN). 

This dose-finding trial is analysing I/ONTAK administered before tisagenleucel (KYMRIAH) CAR-T therapy in diffuse large B-cell lymphoma (DLBCL) patients. 

The first patient in the study was enrolled in May last year.

A recombinant fusion protein, I/ONTAK merges the interleukin-2 (IL-2) receptor binding domain and diphtheria toxin fragments. 

Pembrolizumab is a PD-1 checkpoint inhibitor. 

Citius Pharmaceuticals chief medical officer Dr Myron Czuczman said: “Preclinical research in a syngeneic solid tumour mouse model shows that E7777 [denileukin diftitox] enhances anti-tumour activity and significantly extends the survival benefit of anti-PD-1 therapy. 

“This data provides a positive signal of denileukin diftitox’s potential in the immuno-oncology space.”

In May this year, the company selected clinical research organisation Biorasito aid in expanding its Phase III Mino-Lok trial of a new antibiotic lock therapy to further sites outside the US. GR-CIS supported Biorasi to get Phase III Clinical trial approval in India

All three tested doses of ABP-450 were found to be generally safe and well tolerated.

AEON Biopharma has reported positive topline data from its Phase II clinical trial of ABP-450 (prabotulinumtoxinA) to treat cervical dystonia (CD).

The double-blind, randomised, placebo-controlled trial evaluated 57 subjects at 20 US sites. 

Subjects were categorised into four cohorts to receive either a low dose (150 units), mid-dose (250 units), or high dose (350 units) of ABP-450 or a placebo. 

They were then followed up for 20 weeks, with the primary efficacy endpoint evaluated at four weeks following dosing. 

According to the findings, the trial met the primary and secondary endpoints, with statistical significance in lowering CD-linked signs and symptoms in adults.

All three tested doses of ABP-450 were demonstrated to be generally safe and well tolerated.

The treatment’s adverse event rates were in line with, or less than, other botulinum toxin products for treating cervical dystonia. 

In the trial, mild or moderate treatment-related adverse events were observed, without any serious adverse events. 

ABP-450 is a botulinum toxin complex. It comprises a bacterium Clostridium botulinum-produced 900 kDa botulinum toxin type-A complex. 

The therapy is licenced from Daewoong Pharmaceutical and AEON holds the exclusive development and supply rights of ABP-450 for therapeutic indications in some territories, including the US, Canada, and the European Union, among others.

AEON Biopharma president and CEO Marc Forth said: “We’re pleased to announce the topline data from the Phase II of ABP-450, as we continue to develop prabotulinumtoxinA injection for treatment of debilitating medical conditions, including cervical dystonia. 

“These overwhelmingly positive data confirms that ABP-450 has a therapeutic profile that is consistent with, or exceeds, that of other botulinum toxin products and gives us renewed confidence in our other indications for migraine prevention and treatment of gastroparesis.”

The company plans to hold an end-of-Phase II meeting with the US Food and Drug Administration in the first quarter of next year.

AEON also intends to begin the Phase III programme for CD next year.

A chronic and debilitating neurologic condition, CD impacts the neck muscles.

Eisai and Biogen reported that lecanemab met the primary endpoint as well as all key secondary endpoints of the trial with statistical significance.

Eisai and Biogen reported positive data from a Phase III clinical trial of the anti-amyloid antibody lecanemab (BAN2401) to treat Alzheimer’s disease (AD)-associated mild cognitive impairment and mild AD with established amyloid pathology in the brain.

According to topline results, lecanemab met its primary endpoint of change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) over 18 months in the 1,795-patient Phase III Clarity AD trial (NCT03887455). Lecanemab treatment reduced clinical decline relative to a placebo by 27% along CDR-SB, representing a score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat population. CDR-SB is an 18-point scale that combines cognitive and functional outcomes to measure the severity of dementia symptoms.

Lecancemab is the first of a series of high-profile AD trial readouts expected at the end of 2022 and early 2023. The antibody targets amyloid plaque accumulation in the brain, a popular yet controversial therapeutic target in AD. Biogen’s Aduhelm (aducanumab), which also targets amyloid plaque, has faltered in the market after gaining FDA accelerated approval in July 2021.

Clarity AD also met all key secondary endpoints of ariation from baseline in amyloid positron emission tomography (PET) using Centiloids, AD Assessment Scale-Cognitive Subscale 14 (ADAS-cog14), and AD Composite Score (ADCOMS) at 18 months. In the lecanemab and placebo arms, the occurrence of amyloid-related imaging abnormalities-oedema/effusion (ARIA-E) were 12.5% and 1.7%, respectively.

Eisai plans to seek marketing authorisations in Japan and Europe, as well as a traditional approval for the antibody in the US by the end of March next year. 

In yesterday’s press release, Eisai CEO Haruo Naito said: “The lecanemab Clarity AD study results prove the amyloid hypothesis, in which the abnormal accumulation of Aβ in the brain is one of the main causes of Alzheimer’s disease when targeted with a protofibril-binding therapy. Eisai believes these findings will create new horizons in the diagnosis and treatment of Alzheimer’s disease as well as further activate innovation for new treatment options.”

An investigational humanised monoclonal antibody, lecanemab attaches to neutralise and remove soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils). In November last year, the companies reported that Aduhelm (aducanumab-avwa) substantially lowered plasma p-tau181 in Phase III EMERGE and ENGAGE trials.

TOKYO and CENTER VALLEY, PA., Sept 28, 2022 – (JCN Newswire) – Olympus Corporation (Olympus), a global medtech company committed to making people’s lives healthier, safer, and more fulfilling, today announced the release of the THUNDERBEAT(TM) Open Fine Jaw Type X surgical energy devices for open surgery. With a new thermal shield, the THUNDERBEAT Open Fine Jaw Type X surgical energy device is designed to support safer procedures.[i] The device is available commercially in Japan. The commercial launch of the product in Europe, the U.S., and South Korea is expected in October 2022, with continued launches in other countries and regions following.

This device is part of Olympus’ THUNDERBEAT portfolio of hybrid energy devices that deliver both ultrasonic and bipolar energy simultaneously for tissue management, including hemostatic cutting and dissection, in laparoscopic surgery and open surgery. The THUNDERBEAT hybrid devices eliminate the need for multiple instruments during the surgery, contributing to efficiency in the operating room and reduced operation time.[ii]

“This latest addition to our differentiated THUNDERBEAT line of products continues to deliver on Olympus’ commitment to offering hospitals a full portfolio of Advanced Energy devices providing best-in-class functionality for numerous procedures and specialties in minimally invasive and open surgery,” said Phil Roy, Global Vice President and General Manager of the Surgical Devices Business Unit.

The THUNDERBEAT(TM) Open Fine Jaw Type X device is designed for open surgical procedures that require delicate and fine tissue dissection, such as in thyroidectomy or radical neck dissection. The new thermal shield improves the thermal profile on the grasping surface, which reduces the risk of unintended heat damage to nearby tissue, nerves and other structures.[i] The jaw design maintains a finely curved tip for precise dissection and enhanced visibility during use.[i]

– New Thermal Shield Supports Safer Procedures
The newly developed thermal shield at the distal tip slows heat transfer from the probe to the exterior surface of the jaw and reduces the risk of unintended heat damage to surrounding tissue and vessels.[i]

– Fine Shape of Distal Tip Supports Precise Procedures
The slim shape of the distal tip supports precise tissue management capabilities including fine dissection and firm grasping force, cutting and sealing to the tip of the device, and blunt dissection.[i]

– Simultaneous Output of Two Energies Enables a Variety of Operations with One Device
Delivering simultaneous bipolar and ultrasonic energy enables fast, hemostatic cutting, easy dissection, and reliable vessel sealing and division. A separate advanced bipolar[i] function enables vessel sealing and spot coagulation without cutting, when desired.

The THUNDERBEAT(TM) Open Fine Jaw Type X device is a single use hybrid ultrasonic and bipolar electrosurgical instrument intended for use in open surgery. This device should not be used for tubal sterilization or tubal coagulation for sterilization procedures. Use with caution in patients with electronic implants, such as a cardiac pacemaker, or nerve simulators, to avoid possible hazard to patients due to interference. Before use, thoroughly review the product manual and use the equipment as instructed.

The THUNDERBEAT Open Fine Jaw Type X device is manufactured by Olympus Medical Systems Corporation.

California biotech Calibr and partner AbbVie have reported the first clinical data on a new CAR-T technology, which uses “switchable” cells that aim to eliminate the life-threatening side-effects that can occur with this type of immunotherapy.

Like other CAR-Ts, Calibr’s therapy is manufactured from a patient’s own T-cells, which are harvested and genetically modified to fight cancer before being reintroduced into the body. However, they have a novel molecular switch – in this case an antibody – which activates them only when needed, to avoid the side effects seen with this class.

CAR-Ts can sometimes cause cytokine release syndrome (CRS), when the immune system goes into overdrive and causes dangerous inflammation, which means patients have to receive prophylactic immune-suppressing drugs that can limit the efficacy of treatment.

Scripps Research Institute spin-out Calibr’s lead candidate combines CLBR001 cells – billed as a “universal” CAR-T because they are not targeted at a specific antigen – and companion antibody SWI019, which directs them to CD19 antigens on B-cell cancers. In the absence of the antibody, the CAR-T cells are dormant.

The first readout from an ongoing phase 1 study reveals that, out of nine patients treated to date, seven (78%) showed a response to the treatment, with six (67%) having a complete response, with most responses coming after a single dose of the CAR-T and SWI019.

That remarkable level of efficacy – given that patients had already experienced around five prior lines of therapy – came without an increase in CRS or immune effector cell-associated neurotoxicity syndrome (ICANS), another complication seen with current CAR-T therapies.

“Patients who experienced CRS or ICANS had shorter duration of these events, compared with those in pivotal trials for commercial CAR-T cell products,” said Calibr in a statement.

The duration of those side effects was limited to around 2 to 3 days with the switchable therapy, compared to five to 17 days with already-approved CD19-targeted CAR-Ts, such as Novartis’ Kymriah (tisagenlecleucel), Gilead Sciences’ Yescarta (axicabtagene ciloleucel) and Bristol-Myers Squibb’s Breyanzi (lisocabtagene maraleucel).

There is also evidence that responses can be deepened with repeat administrations of the SWI019 antibody, which deliberately has a relatively short half-life to minimise the risk of side effects, said Calibr.

“These results underscore the potential of Calibr’s switchable CAR-T cell platform to act like a ‘software’ and ‘hardware’ approach, where the biological response of the CLBR001 cell ‘hardware’ can be programmed using the switch dose as the ‘software’,” said Travis Young, head of biologics at Calibr.

“This is our first step toward demonstrating the potential of this universal platform to be programmed toward any target, including those for solid tumours,” he added.

So far, conventional CAR-Ts have not been effective in treating solid tumours because of difficulties in targeting tumours, surviving the hostile microenvironment around them, and infiltrating them to exert their anti-cancer effects.

Calibr hopes its approach could, however, overcome those limitations with higher doses of targeting antibody or potentially multiple antibodies targeting different tumour-associated antigens.

AbbVie has been involved in the development of the switchable CAR-T platform since 2018, when it licensed the technology for various tumour targets in return for an undisclosed upfront fee. It has option to license some of Calibr’s existing cell therapy programmes, including CLBR001+ SWI019.

Other companies are also investigating ways to enhance the efficacy of CAR-Ts. Earlier this month, for example, BioNTech reported results with its “amplified” CAR-T BNT-211 for solid tumours, which consists of cells directed at Claudin-6 on cancer cells, coupled with an mRNA vaccine designed to amplify their activity.

UK start-up Leucid Bio, meanwhile, is developing CAR-Ts that are engineered in a more natural biological configuration that is designed to enhance their potency, extend responses, and reduce side effects.

Other research groups are using a similar switchable approach to activating the cells, using triggers including small-molecule drugs, viruses, and even light and heat.

French pharma company Genfit has reached a deal to buy Versantis of Switzerland, adding three development-stage drug candidates to its portfolio of experimental liver disease therapies and continuing a strategy change first unveiled in 2020.

That change was forced by disappointing clinical trial results with Genfit’s lead drug elafibranor in non-alcoholic steatohepatitis (NASH), and included a pledge to build a pipeline in rare liver diseases behind elafibranor – now redirected at primary biliary cholangitis (PBC), a chronic autoimmune disease in which bile ducts in the liver are gradually destroyed, causing cirrhosis.

Pascal Prigent, Genfit’s chief executive, said on a conference call today that the deal consolidates its position in acute-on-chronic liver failure (ACLF); in other words, acute exacerbations that occur in the late-stages of chronic liver disease and can lead to multiple organ failures.

ACLF generally requires urgent medical intervention, with a mortality rate of 23% to 74% at 28 days, depending on the degree of organ failure, with around 37,000 cases having lead to hospitalisations last year in the US. And with no approved drugs, therapies that treat it may be open to quicker passage through regulatory review, said Prigent.

Versantis’ drug candidates fulfil that brief, and include a phase 2-ready programme called VS-01 for ACLF, as well as rare paediatric disease urea cycle disorder (UCD) – which Genfit estimates could be a billion-dollar indication on its own.

The liposome-based therapeutic is designed to clear toxic metabolites, such as ammonia, from the body by extracting them from the blood into the abdominal cavity, where they are drained away.

“VS-01 has the potential to be the first drug to use the intraperitoneal  route to simultaneously support the liver, kidney, and brain – the organs that most often fail in cirrhotic ACLF patients,” said Prigent.

Following after is VS-02, a preclinical-stage small-molecule drug being developed for the chronic management of a complication of ACLF, known as hepatic encephalopathy (HE), which can lead to coma and death. There is also TS-01, a point-of-care diagnostic device in prototype development for the at-home measurement of ammonia in the blood, the primary cause of HE. Genfit thinks HE could be a $2 billion market opportunity.

“Versantis has an exciting portfolio that is complementary to Genfit’s,” Prigent told investors, pointing to its own nitazoxanide (NTZ) candidate, which has phase 1 data in hand and is also being developed for ACLF.

“We believe that significant synergies exist and that this acquisition will accelerate the development of several promising drug candidates in areas of high unmet needs,” he added.

The acquisition of Versantis has been funded in  part as a result of a €480 million licensing deal with Ipsen, in which Genfit handed over rights to its PPAR agonist elafibranor – also in trials for PBC – which included a €120 million upfront payment.

The financial terms of the deal, due to complete in the fourth quarter, includes an upfront payment of CHF 40 million and CHF 65 million in milestones, with Versantis’ shareholders also in line for a one-third share of proceeds from a priority review voucher (PRV) that may be forthcoming from the FDA if VS-01 gets approved.

PRVs can be sold on to other companies and typically have a market value of around $100 million.

It’s well known that where you live can have a profound impact on your risk of heart attack or stroke, but the exact reasons behind that inequality can be hard to tease out.

Now, a collaboration between drugmaker Novartis, Microsoft, and New York University (NYU) intends to use artificial intelligence (AI) to investigate the factors behind the observation that a person living in one neighbourhood can have a greater risk of heart disease and poorer outcomes than another living mere streets away.

The initiative – called the AI4HealthyCities Health Equity Network – is kicking off in New York City and will use data and analytics to target heart health inequity, and hopefully guide public health authorities towards strategies that can level the playing field for patients.

The plan is to roll the programme out into other cities around the world later this year.

It’s intuitive to think that neighbourhood features – such as healthcare resources, healthy food options, and facilities for physical activity – may be particularly important in patients with chronic conditions, such as heart disease.

According to NYU researcher Dr José Pagán, where people live and work in New York, as well as their degree of social and economic disadvantage, has a bigger impact on their risk of developing cardiovascular disease than their access to healthcare.

For example, previous research has found wide disparities in heart health in NYC, with premature death rates from heart disease 2.4 times as high in the poorest areas compared to the richest, and 1.8 times higher among black compared to white adults.

“This initiative will give us better insights into the cardiovascular health of New Yorkers in an effort to identify the most pressing issues to address and shape our city’s policies,” he said.

Microsoft’s AI will do the heavy lifting, examining anonymised data on the conditions in which people are born, grow, work, and age in the city, to find variables that are predictive of cardiovascular disease and a poorer outcome after diagnosis.

Housing, access to healthy food, physical exercise or green space, education, professional occupation, pollution, migration, and the influence of structural racism and ageism are all variables that will be taken into account during the project.

That could help urban policymakers better target health resources towards the interventions that could have the greatest impact on heart health, said the partners.

“Whether at a global or local level, health inequities are shaped by economic status and access to resources,” according to Dr Ann Aerts, head of the Novartis Foundation.

“In New York and other cities, we believe that data and AI-driven insights can help stakeholders make informed decisions on impactful urban heart health interventions that ultimately reach the greatest number of people.”

The project extends the work of the Novartis Foundation – a non-profit arm of the Swiss pharma group – in population-wide measures to improve health and reduce inequalities.

It is already running a scheme, called CARDIO4Cities, which lays out a toolkit of best practices that cities can adopt to reduce cardiovascular risk in their citizens.

A pilot of the approach has been conducted in three cities – São Paulo, Dakar, and Ulaanbaatar – and tripled blood pressure control rates, sometimes improving on rates achieved in European countries.

It is due to be extended into additional cities, including Ho Chi Minh City, and expanded to include other cardiovascular risk factors including high cholesterol, diabetes, and obesity.

In 2020, a report from the Novartis Foundation and Microsoft concluded that health systems in lower-income countries could overtake those in richer countries with AI-enabled technologies.

Findings from the litifilimab trial, undertaken by Northwell Health’s Division of Rheumatology and The Feinstein Institutes for Medical Research, have been published in the New England Journal of Medicine and show promise for those who have been diagnosed with systemic lupus erythematosus (SLE).

Sponsored by Biogen Inc., data from the phase 2 LILAC (Part A) clinical trial published this month shows that the experimental lupus therapy could reduce disease activity in the joints of patients, globally improving their condition.

Evaluating the extent of the efficacy and safety of the investigational monoclonal antibody drug litifilimab (BIIB059) in two parts, Part B results from the randomised, double-blind, placebo-controlled trial were published in July this year and looked at the effects of litifilimab on patients with cutaneous lupus erythematosus (CLE).

Principal investigator of the study, Dr Richard Furie, professor at the Feinstein’s Institute of Molecular Medicine, said, “Patients live with SLE their entire lives and experience chronic inflammation, pain, and potentially organ failure.” Litifilimab could offer a lifeline.

Dr Furie has also lead other clinical trials resulting in FDA approval of new therapies for SLE, including Saphnelo (anifrolumab), as well as Benlysta (belimumab) for lupus nephritis – the first therapy approved for treatment of that form of lupus.

Around 1.5 million people in the US alone are living with systemic lupus erythematosus. In SLE, sufferers’ immune systems attack their body’s own tissues, resulting in widespread inflammation and damage to affected organs, including the joints, skin, lungs, kidneys, blood vessels, and brain. There is currently no known cure for lupus.

“The results from this trial show that litifilimab may effectively block the body’s production of harmful inflammatory molecules in people with SLE, easing their joint pain and improving overall disease activity,” Dr Furie said.

Partaking in the study were 132 participants. They were either given 450mg of litifilimab or the placebo subcutaneously every four weeks for a period of 20 weeks. An additional does was given at week two. It was determined that there was a greater reduction in swollen and tender joints in those on litifilimab than the placebo over a period of 24 weeks.

Further and longer trials are needed, and Biogen Inc. is presently enrolling two phase studies in 31 countries worldwide. A pivotal study in CLE will also be initiated later this year.

Dr Kevin J. Tracey, president and CEO of Feinstein Institutes and Karches Family distinguished chair in medical research, remarked, “this clinical trial may lead to a new and much-needed option for combatting inflammatory cytokines that worsen the disease.”

Earlier this year, Akili released results from its clinical trial AKL-T01, looking at the efficacy of digital therapeutics (DTx) in managing the cognitive impairments that patients with SLE can be affected by.

Aurinia Pharma and partner Otsuka have secured approval in the EU for Lupkynis, billed as the first oral treatment for active nephritis in patients with the autoimmune disease systemic lupus erythematosus.

Kidney inflammation caused by SLE is referred to as lupus nephritis (LN), and it is estimated that between 40% and 50% of all SLE patients will develop LN that requires treatment over the course of their lifetime.

Lupkynis (voclosporin) has been cleared by the European Commission for use in combination with immunosuppressant mycophenolate mofetil (MMF) for adult patients with moderate to severe (class III to V) LN.

It was approved in the US with a similar label last year after priority review, becoming the first oral alternative to GSK’s injectable anti-BLyS/BAFF antibody Benlysta(belimumab) for the treatment of active LN, although other unapproved drugs are used to treat the condition.

Lupkynis is in the well-established calcineurin inhibitor class of immunosuppressants, which includes oral drugs like cyclosporine and tacrolimus that have both been used off-label to treat LN.

The new drug is thought to have a dual mechanism of action, acting as an immunosuppressant through inhibition of T-cell activation and cytokine production, and promoting podocyte stability in the kidney.

The EU decision is based on the data from the phase 3 AURORA 1 and 2 studies, which showed that treatment with voclosporin in combination with MMF and low-dose corticosteroids achieved superior renal responses at 52 weeks compared to MMF and low-dose corticosteroids alone, with a comparable safety profile.

A decision in Great Britain is expected from the UK Medicines and Healthcare products Regulatory Agency (MHRA) in the coming weeks, according to an Otsuka statement. Meanwhile, Lupkynis has also been filed with the Swiss Agency for Therapeutic Products and is currently under review.

Otsuka licensed rights to Lupkynis in various ex-US markets including the EU, Japan and the UK in 2020, with Aurinia retaining rights to the drug in the US and its home market of Canada.

In the US, the product launched with a wholesale acquisition cost (WAC) of $3,950 per 60 capsules – enough for around 10 days’ treatment, with the cost per patient per year estimated at around $65,000.

Aurinia reported Lupkynis sales of around $50 million in the first half of this year, and has previously said it expects full-year revenues from the drug to reach $115-$135 million, assuming EU approval.

The company is facing a patent challenge from India’s Sun Pharmaceuticals relating to a dosing protocol used for LN, which is expected to lead to a judgment from the US Patent Office (USPTO) next July.