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Iovance Biotherapeutics is facing a three-month delay in the review of its lifileucel cell therapy for melanoma in the US, held up by “insufficient resources” at the FDA.

The new data has been extended from 25th November to 24th February next year, although Iovance said the FDA has said it will “expedite the remaining review for a potentially earlier approval date.”

The biotech filed tumour-infiltrating lymphocyte (TIL) therapy lifileucel as a one-time, individualised therapy for people with advanced melanoma in May, and was awarded a priority, six-month review by the FDA, with no advisory committee meeting required.

Iovance said the priority review remains in place, adding that the FDA had reassured it that there were no major review issues with the marketing application and all pre-approval inspections of clinical, manufacturing, and testing sites have been completed. The delay resulted from a lack of capacity to deal with the response to a request for additional information.

It also said the FDA has no concerns with the TILVANCE-301 in frontline advanced melanoma, designed to be a confirmatory trial for accelerated approval, which should be “well underway” by the new decision date.

Iovance is leading the charge among biopharma companies trying to bring cell therapies to market for solid tumours and mirror the success achieved with CAR-Ts in haematological cancers.

Like a CAR-T, lifileucel is derived from lymphocytes that are harvested from individual patients, expanded in the lab, and then reinfused to fight the cancer. Unlike CAR-T therapies, however, the cells don’t need to be genetically modified, merely exposed to IL-2 to activate them, which makes the manufacturing process shorter.

Iovance’s filing covers the use of the therapy for patients with advanced melanoma who progressed on or after prior anti-PD-1/L1 therapy and targeted therapy, where applicable. There are currently no FDA-approved therapies in this treatment setting, according to the company.

Its filing is based on the results of the C-144-01 study, which showed lifileucel achieved a 36% objective response rate (ORR) with a duration of response of 36 months in these patients, leading to predictions of blockbuster sales for the cell therapy.

That initial optimism has been somewhat dented by follow-up data that raised questions about lifileucel’s durability, with an ORR of 29% for a second cohort in the study and a duration of 10.4 months. GlobalData is currently predicting US sales will peak at around $722 million.

“We appreciate FDA management’s efforts to expedite the remaining review so that we can bring lifileucel to critically ill patients with no other FDA-approved options after current standard of care,” said Iovance’s chief executive, Frederick Vogt.

“We are confident in the potential for lifileucel to redefine the treatment paradigm for these patients.”

Shares in the company dipped on the delay, but were on the rise this morning as investors responded to the positive elements in the update and the agency’s reported willingness to complete the review as quickly as possible.

Anteris Technologies has revealed that a successful procedure of its DurAVR transcatheter aortic valve (THV) took place in a Canadian study as the company continues to build up positive clinical evidence for the device.

Implanted in patients as part of Health Canada’s Special Access Programme that allows life-saving technology not currently available to be used when no other treatments are suitable, the device is what Anteris claims is the world’s only balloon-expandable, single-piece THV.

The Australian medical device company recently announced the start of a US early feasibility trial(NCT05712161) in patients with aortic stenosis for the implant, which is made from a single piece of bioengineered tissue with anti-calcification properties.

Dr Janar Sathananthan, who made the request to Health Canada and is an interventional cardiologist at Vancouver General and St Paul’s Hospital, said: “Today’s case demonstrated what we saw in preclinical testing, that DurAVR THV has the potential to offer superior gradients for valve-in-valve patients. This is a great result in a small surgical valve at high risk for elevated gradients.”

Anteris is also conducting an early feasibility study in Europe (CT05182307) testing the device in patients with aortic stenosis. As per the ClinicalTrials.gov entry, the trial is expected to be completed in Q4 2023.

Anteris Technologies CEO Wayne Paterson said: “As the body of evidence is growing rapidly with our Europe and North American patients, we are seeing results that support both the clinical and commercial case for DurAVR THV.

“Our continued clinical success both in the treatment of native aortic stenosis patients as well as the complicated and difficult-to-treat valve-in-valve patients is building confidence within the global physician community.”

China-based QiLu Pharmaceutical has announced positive data from a Phase III trial investigating iruplinalkib in patients with non-small cell lung cancer (NSCLC).

The data analysis showed that the primary endpoint of progression-free survival (PFS) met the pre-defined criteria. Additionally, PFS in the treatment group was significantly improved compared to the comparator cohort, with a median PFS of 27.7 months and 14.62 months, respectively.

Iruplinalkib also showed superior results compared to crizotinib, which was a comparator in this trial, in the secondary endpoints such as duration of response (DoR) and control of intracranial disease. Iruplinalkib retained its safety profile that was established in previous studies.

INSPIRE trial design

The open-label randomised INSPIRE trial (CTR20191231) enrolled 292 patients with ALK-positive NSCLC who had not been previously treated with ALK tyrosine kinase inhibitors.

The trial evaluated the safety and efficacy of oral 180mg once-daily dose of iruplinalkib versus oral 250mg twice-daily dose of crizotinib. The treatment cohort had a seven-day lean-in phase of 60mg once-daily dose of iruplinalkib.

The trial was conducted across 40 hospitals in China and led by investigator Yuankai Shi, a professor at the Cancer Hospital Chinese Academy of Medical Sciences.

On 28 June, the China National Medical Products Administration (NMPA) approved QiLu’s oral iruplinalkib for market launch to treat patients with metastatic ALK-positive NSCLC who had progressed or are intolerant to crizotinib.

QiLu has already submitted a new drug application for iruplinalkib as a first-line treatment for the same patient population. The application has been accepted by the NMPA’s Center for Drug Evaluation.

QiLu’s NSCLC pipeline

QiLu has two other ongoing Phase III clinical trials in NSCLC that are investigating QL1706. QL1706 is a bifunctional antibody for immunotherapy that is a combination of iparomlimab and tuvonralimab.

The DUBHE-L-304 (NCT05487391) is a randomised, double-blind, placebo-controlled trial. QiLu plans to enrol 632 patients with completely resected stage II-IIIB NSCLC without EGFR-sensitive mutations and ALK fusion genes.

Participants will receive 16 cycles of QL1706 or placebo in combination with two to four cycles of adjuvant chemotherapy. The primary endpoints are measuring investigator-assessed disease-free survival (DFS).

The double-blind, randomised, active-controlled DUBHE-L-303 (NCT05690945) trial plans to enol 650 patients with PD-L1-negative, stage IIIB-IV NSCLC without EGFR/ALK mutations.

Patients will receive either four cycles of QL1706 or tislelizumab plus chemotherapy. This will be followed by maintenance treatment with QL1706 or tislelizumab. The primary endpoints are evaluating PFS and overall survival.

Both DUBHE trials are conducted in research centres across China.

Alphabet precision health technology company Verily and OneOncology have announced a strategic collaboration for clinical trials.

Under the partnership, community OneOncology Research Network sites will get access to new tools for expediting trials and improving their cancer care delivery.

Verily’s clinical trial management software (CTMS) platform SignalPath will be integrated across practices in OneR, the OneOncology Research Network, as part of the agreement.

Using next-generation protocol digitisation technology, SignalPath will configure and systematise study protocol workflows and save time and effort of the site staff.

It helps improve the complexities, costs and time associated with running clinical trials and optimises for quality and time with participants.

OneOncology chief medical officer Dr Davey Daniel said: “Clinical trial research is core to high-quality cancer care programmes.

“By using technology to create a platform offering from OneR, we can help enhance our partners’ clinical trial programmes, which ultimately better democratises clinical trials, and improves health equity.”

OneOncology plans to further develop connected solutions across its research and care product offerings and will continue to collaborate with Verily.

In September 2021, Verily concluded the acquisition of SignalPath, boosting its clinical research capabilities.

Phase I/II trials for Ocugen’s gene therapies, OCU410 and OCU410ST, are planned for initiation by the end of 2023 in geographic atrophy and Stargardt disease.

The plans follow the US Food and Drug Administration’s (FDA) approval of the Investigational New Drug (IND) application for the two gene therapies.

Ocugen is also planning for a Phase III trial in retinitis pigmentosa for OCU400 in Q4 2023/Q1 2024. The Phase III trial initiation is contingent on the FDA’s approval of trial plans and Phase I/II data.

OCU410ST was granted the orphan drug designation by the FDA for the treatment of Stargardt disease. Also known as ABCA4 retinopathy, the illness is a rare genetic disorder caused by pathogenic variations in the ABCA4 gene leading to fatty build-up on the macula and loss of vision.

OCU400 is an adeno-associated virus serotype 5 capsid containing the gene for human nuclear hormone receptor NR2E3. It is being developed in partnership with China-based CanSinoBIO. It is currently being evaluated in an open-label Phase II trial (NCT05203939).

An open-label Phase I trial (NCT05802329) for OCU200 in patients with diabetic macular oedema was initiated in Q2 2023. One of the cohorts in the trial will evaluate the combination therapy of OCU200 and Novartis’ Lucentis (ranibizumab).

Ocugen announced that the manufacturing facility for its regenerative cell therapy for cartilage, NeoCart, is expected for completion by the end of 2023, with a Phase III trial for the therapy planned for initiation in H2 2024.

As part of their second quarter financials, Ocugen reported cash equivalents of $70.6m on 30 June 2023. The company also reported a loss of $0.10 per common share in Q2 2023.

The FDA has approved BioMarin’s Roctavian (valoctogene roxaparvovec) for adults with severe haemophilia A.

Currently, around half of the patients who have the most severe form of haemophilia A undergo intravenous Factor VIII (FVIII) infusions two to three times per week, or receive a bispecific monoclonal antibody one to four times per month. However, many patients still suffer from bleeds, leading to incapacitating joint damage. Addressing this unmet need, BioMarin’s Roctavian is administered as a solitary infusion and delivers a functional gene that enables the body to independently produce FVIII. This innovative approach reduces the treatment burden by eliminating the need for continuous haemophilia prophylaxis.

The authorisation was granted based on the results of the Phase III GENEr8-1 clinical trial. This study assessed the effectiveness and safety of Roctavian in a group of 134 adult males afflicted with severe haemophilia A. Each participant was given a solitary intravenous infusion of Roctavian and subsequently monitored for a period of three years. Among the 134 patients enrolled in the study, baseline annualised bleeding rate (ABR) data was collected for 112 patients prospectively, covering a minimum period of six months while they were on FVIII prophylaxis before receiving Roctavian. The remaining 22 patients had their baseline ABR data collected retrospectively. After receiving Roctavian, the 112 patients for whom six-month baseline ABR data was prospectively collected witnessed a noteworthy average reduction of 52% in ABR (equivalent to 2.6 bleeds per year) during the follow-up period. This reduction is in comparison to their baseline ABR while receiving routine FVIII prophylaxis (equivalent to 5.4 bleeds per year). Moreover, these patients reported a significant decrease in the occurrence of joint pain and spontaneous bleeds following their treatment with Roctavian.

BioMarin’s Roctavian will face a distinctive challenge, setting it apart from the numerous gene therapies already approved by the FDA. Unlike therapies that are targeted at conditions with limited alternatives, Roctavian enters a competitive market saturated with many successful haemophilia A treatments; one such example is Roche’s blockbuster antibody drug Hemlibra (emicizumab-kxwh), which generated sales of $4m in 2022. Accordingly, GlobalData estimates global sales of $1.21bn by 2029 for Roctavian.

Astellas Pharma Inc has announced that the US Food and Drug Administration (FDA) has accepted and granted Priority Review of its zolbetuximab Biologics License Application (BLA). If approved, the first-in-class investigational Claudin 18.2 (CLDN18.2)-targeted monoclonal antibody would be the first CLDN18.2-targeted therapy available in the US for patients with advanced gastric and gastroesophageal cancers.

Gastric cancer, more commonly known as stomach cancer, is the fifth most diagnosed cancer in the world. In the US alone, roughly 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023. Frequently, early-stage gastric cancer symptoms overlap with more common stomach-related conditions. This often results in gastric cancer diagnosis occurring in the advanced or metastatic stage, or once it has spread from the tumour origin to other body tissues or organs.

The five-year survival rate for patients at the metastatic stage is 6.6%.

Zolbetuximab is intended for first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours are CLDN18.2-positive. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

The BLA is based on results from the phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 – a combination regimen that includes oxaliplatin, leucovorin, and fluorouracil – compared to placebo plus mFOLFOX6.

The GLOW study evaluated zolbetuximab plus CAPOX – a combination chemotherapy regimen that includes capecitabine and oxaliplatin – compared to placebo plus CAPOX.

In both studies, approximately 38% of patients screened for the trials had tumours that were CLDN18.2-positive, as determined by a validated immunohistochemistry assay.

The FDA reviewed the application under its Real-Time Oncology Review (RTOR) programme, which aims to explore a more efficient review process to ensure that safe and effective treatments are made available to patients as early as possible.

Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of 12th January 2024 and Astellas has already reflected the impact of this acceptance in its financial forecast of the current fiscal year ending 31st March 2024.

Moitreyee Chatterjee-Kishore, senior vice president and head of immuno-oncology development at Astella, said: “Astellas is committed to bringing innovative therapies to patients with hard-to-treat cancers, including gastric cancer […] The FDA’s acceptance of the Biologics License Application filing and Priority Review designation for zolbetuximab confirms the urgent therapeutic need and brings us one step closer to delivering on this commitment to patients, families, and caregivers.”

A digital tool developed by researchers in the NHS that is being used to speed up the diagnosis of heart disease has won this year’s Future NHS Award, which recognises outstanding contributions from the health service workforce.

The artificial intelligence-powered tool was developed by doctors and scientists from Sheffield Teaching Hospitals and the University of Sheffield’s Insigneo Institute and is designed to evaluate the heart function of a patient and identify damage to heart tissue in just a few seconds using MRI scans.

It automatically detects the heart’s function using an algorithm that performs analytical tasks on more than 180 images taken from a patient’s MRI scan, which otherwise would need to be carried out manually.

The tool was described by Sheffield MP Clive Betts, who nominated it for the NHS Parliamentary Award, as a potential ‘game changer’ in future heart disease care, speeding up the diagnosis, treatment, and care of patients.

Betts said the technology “is already leading to more speedy identification of problems and is therefore reducing waiting times for treatment.”

In addition to providing a measure of heart function, the AI can also monitor changes in pressure that take place over the course of the cardiac cycle, providing more detailed information about the flow of blood in and out of the heart.

That, in turn, allows clinicians to identify and spot where the heart’s function may be disrupted at a level of detail previously not available.

The team behind the AI comprises Sheffield Teaching Hospitals’ scientific and innovation director Professor Wendy Tindale OBE, consultant radiologist Dr Kavitasagary Karunasaagarar, consultant cardiothoracic radiologist Dr Andrew Swift, clinical scientist Dr Pete Metherall, and Michael Sharkey, University of Sheffield senior research scientist in AI.

“The fully automatic cardiac MRI segmentation analysis has already made significant strides in improving both the efficiency and precision of cardiac MRI analysis,” commented Dr Karunasaagarar.

“This distinguished recognition underlines the commitment our team has shown in revolutionising healthcare through technological innovations.”

Other winners in the NHS Parliamentary Award included an integrated frailty service reducing pressure on hospitals in Warwickshire, a reproductive trauma service supporting pregnant women with mental health challenges in Lancashire and South Cumbria, and a prostate self-referral service set up to help increase prostate cancer referrals in the Southampton area after the pandemic.

“It is thanks to the doctors and nurses, the porters and the cleaners, social care workers, physiotherapists, ambulance crews – and everyone else – that the NHS continues to be our national treasure,” said Health and Social Care Secretary Steve Barclay at the awards ceremony.

“So much has been achieved within healthcare over the past 75 years, and they are helping to build a stronger, healthier service for the long term,” he added.

Yesterday the US Food and Drug Administration granted full approval to Eisai and Biogen’s Leqembi (lecanemab-irmb), making it the first approved Alzheimer’s treatment clinically shown to slow disease progression and cognitive and functional decline. Though these benefits are modest – Leqembi reduced clinical decline on the  Clinical Dementia Rating Sum of Boxes (CDR-SB) by 27% at 18 months compared to placebo – they are nonetheless a significant milestone in treatment for the neurodegenerative disease.

Under the approved Biologics License Application, the drug is cleared to be used intravenously in early AD patients.

Crucially, the announcement was also accompanied by confirmation from the Centers for Medicaid and Medicare Services that it would cover the therapy more broadly in the wake of the decision. Since the controversy surrounding Leqembi’s predecessor, Aduhelm, CMS has been very limited in its coverage of amyloid-targeting Alzheimer’s drugs.

“Today marks a breakthrough in the treatment of Alzheimer’s disease, and we are proud to be at the forefront of ushering in a new era of advances for a disease that was previously considered untreatable. We would like to express our sincere appreciation to those who have worked tirelessly to find a treatment for this unrelenting disease, without whom this progress would not be possible,” said Christopher A. Viehbacher, president and CEO of Biogen, said in a statement. “Our focus is now on the path forward, working alongside Eisai with the goal of making Leqembi accessible to eligible patients as soon as possible.”  

“Alzheimer’s disease is a progressive, fatal disease that greatly impacts not only the people living with it, but also their loved ones, care partners and society,” added Eisai CEO Haruo Naito. “We continue to work to create broad and simple access to LEQEMBI for patients and to support diagnosis and treatment at the early stage of the disease. Eisai will diligently work to educate physicians on the safe and appropriate use of LEQEMBI to maximise its benefit to people living with early AD and their families.”   

Today’s news was expected following the unanimous support Leqembi received from an FDA Advisory Committee last month. The panel found that the risk-to-benefit profile for the drug was acceptable in various patient subgroups, including patients with two copies of apolipoprotein E (ApoE) ε4 gene, on anticoagulants or with cerebral amyloid angiopathy, who seem to be at elevated risk of side effects, and particularly potentially life-threatening amyloid-related imaging abnormalities (ARIA).

Nonetheless, it’s something of a vindication for Eisai and Biogen, whose previous amyloid-targeting drug Aduhelm ended up mired in controversy and ultimately proved a commercial failure. While the safety questions aren’t settled, the outlook is looking decidedly more optimistic, and this approval should bode well for Eli Lilly’s upcoming donanemab as well as further innovation in this space in the future.

Boehringer and Zealand released Phase II data with the investigational drug survodutide, while Novo Nordisk presented new Ozempic data.

At the American Diabetes Association’s 83rd Scientific Sessions, Boehringer Ingelheim and Novo Nordisk took another step in the obesity arena with data presentations on their respective glucagon-like peptide receptor 1 agonist (GLP1RA) trials for diabetes and obesity management.

Boehringer’s survodutide (BI 456906) is a subcutaneous long-acting dual glucagon and GLP-1 agonist that requires administration once weekly. The Germany-based company is developing the therapy with Zealand Pharma for people living with obesity or who have a body mass index (BMI) exceeding 27kg/m² and for treating non-alcoholic steatohepatitis (NASH).

Data from the Phase II dose-finding trial (NCT04667377) showed a dose-response relationship with higher doses of survodutide, which lead to increased weight loss. Furthermore, 82.8% of the participants in the 4.8mg survodutide group achieved a weight loss of at least 5% at week 46 in comparison to 25.9% in the placebo group. The company reported that 90.9% of participants in the survodutide group had adverse events in comparison to 75.3% of the placebo group. Additionally, the drug has shown a nearly 19% efficacy for weight loss in overweight or obese people, as per a 23 June Zealand Pharma release. 

In a press release, Dr Carel le Roux, the principal investigator of the trial explained the drug’s mechanism saying, “By activating both the glucagon and GLP-1 receptors, survodutide may inhibit both appetite and improve energy expenditure.”

Survodutide is being developed under a GLP-1/glucagon dual agonist licensing agreement between the two companies where Boehringer finances all research, development and commercialisation activities. This partnership uses Zealand’s experience in developing peptide-based medicines and the company could possibly receive up to €345m ($376.1m).