On October 5, 2020 Diaceutics PLC, (AIM: DXRX) reported new research which predicts that the Non-Small Cell Lung Cancer (NSCLC) testing market will expand to $3.6 billion in the United States by 2025 – up considerably from just $125 million today (Press release, Diaceutics, OCT 5, 2020, View Source [SID1234568115]). The findings are published in the 2020 Diaceutics PM Readiness Report.

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Driven by the increased utility of NSCLC testing and testing services, as well as new single and combination treatments – Diaceutics’ research found that currently, there are 714 new precision medicine treatments focused on NSCLC in late-stage clinical trials – this exponential growth represents 40% of the total value for the NSCLC treatment market. The growing market demonstrates the mounting dependence on precision medicine therapies for cancer treatment; and the pharmaceutical sector’s increasing investment in testing to ensure that their new treatments reach the eligible patient population. In doing so, they are closing the gap on the $2-3 billion in potential NSCLC revenues that is currently lost every year due to inefficient testing.

Currently, only half of patients with advanced NSCLC are receiving the right drug
As pharma revenues continue to be lost due to hurdles inherent with current NSCLC testing pathways, analysis in Diaceutics’ PM Readiness Report shows that this has a significant impact on patient treatment. Currently, only half of NSCLC patients who are eligible for precision medicine therapies receive them, with not enough emphasis being placed on the economic value of diagnostic testing. Pharma investment therefore often does not reflect the true value of efficient testing, or the investment is spread too thinly across multiple players. This disincentivises stakeholders within the testing ecosystem from addressing the entire patient journey from cough to precision treatment, leading to a fragmented approach to testing.

Diaceutics’ research found that by investing heavily in the PD-L1 22C3 antibody, Merck has shown how education and investment drives biomarker adoption, with 83% of all PD-L1 testing today using Merck’s associated antibody.

Furthermore, 10% of patients receive NSCLC treatment without relevant testing
Diaceutics’ research shows that even when patients do receive a precision medicine drug, one-in-10 will receive the wrong one. The PM Readiness Report found that 10% of NSCLC patients are receiving precision medicine treatments without having had the relevant biomarker tests, signifying a knowledge gap amongst oncologists around biomarkers and their associated treatments.

Progress is being made with PD-L1
Recent guidance from the FDA states that it is continually approving multiple drugs that are dependent on the same biomarkers, and pharmaceutical companies should therefore focus on promoting multiple tests that lead patients to their specific therapies, rather than focusing on one proprietary test.

Diaceutics analysed the value in multiple pharma competitors simultaneously promoting companion diagnostic tests for specific groups of therapies and found significant revenue benefits for pharma. In the case of PD-L1 testing, this approach has reduced the post-launch time it takes for a new biomarker test to reach 80% of the eligible patient population from seven years to three. In the case of EGFR and ALK, however, the average delay remains high at six years due to poor pre-launch preparation.

The impact of COVID-19
The fragility of the testing ecosystem has been highlighted by the emergence of COVID-19 and Diaceutics has observed the pandemic’s highly disruptive impact on cancer testing. It found that cancer testing in China decreased by as much as 50% in Q2 2020 versus the Q2 2019. The company’s tracker in the US also revealed that there was a 31% drop in newly diagnosed cases of lung cancer between February and March 2020. The research revealed that while patients already diagnosed with cancer and receiving treatment were continuing to be supported, the decrease in testing over this period will result in a backlog of undiagnosed patients. The ramifications of this backlog will be felt in 2021 and beyond. Furthermore, the increased pressure on testing laboratories caused by the demand for COVID testing has seen a decentralisation of cancer testing observed across China with regional laboratories having to manage the fallout. As a result, Diaceutics observed that enhanced planning and investment will be critical to absorb what will be a significant increase in testing needs following COVID-19.

Speaking about the findings of the report, Peter Keeling, CEO and Founder of Diaceutics, said: "Patients simply cannot get the right treatment without efficient testing – COVID-19 has unequivocally proven that model to be true and has presented us with an opportunity to get out in front of a global testing crisis which has this year, been put in the spotlight.

"The era of launching a therapy with a single companion diagnostic partner is definitely behind us. We need to consider the global needs of our patients and the regional restrictions which have been further exacerbated by the pandemic. This calls for pharma to think beyond a one-size-fits-all approach and to embrace the democratisation of testing.

"The time has come to eradicate the hurdles that stand in the way of getting patients the treatment they deserve. Our evidence, our partners and our experience tell us that there is a better way and that the time for that better way is now. We believe that a global platform will enable the collaboration required between stakeholders to overcome the hurdles in today’s testing ecosystem.

"Research from the Report shows that a platform like DXRX has the potential to reduce the time to achieve 50% test adoption in NSCLC from the current average of 4.5 years to just months. That would be transformative for patients and could make the promise of precision medicine a reality for more people."

On October 5, 2020 Cancer Research UK reported that Earlier detection of cancer offers arguably the single biggest opportunity to save lives from the disease, but there are many challenges of seeing this a reality for patients in the NHS, according to Cancer Research UK’s Roadmap for the Early Detection and Diagnosis of Cancer report, and highlighted in a commentary in the Lancet Oncology (Press release, Cancer Research UK, OCT 5, 2020, View Source [SID1234568131]).

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Cancer Research UK’s consultation of over 100 experts highlights the siloed early detection research and development ecosystem, from academia and industry to the health services and policy makers, which is hampering progress. It proposes a series of tangible recommendations to unite these sectors, address these challenges and deliver a future where early detection of cancer is a routine reality.

Critically, it calls for the significant investment in diagnostic equipment and technologies, along with NHS staff, to support new ways of working and drive the paradigm shift to diagnose more cancers at an earlier stage, and ultimately save lives. The Roadmap also calls to attention a market failure in early detection of cancer, with too few innovative technologies making into the health system.

By having the right investments and policies in place, the UK has the potential to become a world leader in early detection and diagnosis of cancer, unlocking a major economic growth opportunity for the UK.

The authors hope that the prioritisation of early detection and diagnosis of cancer by scientists, companies, health services and government will create a thriving multidisciplinary ecosystem, focussed on proactively managing patients’ health and wellbeing before symptoms arise.

Dr David Crosby, head of prevention and early detection research at Cancer Research UK and co-author of the Roadmap said: "All too often, patients are being diagnosed at a late stage, where their cancer is deeply rooted and requires significant intervention, often with poor outcomes.

"This is a human tragedy, not just in terms of lives lost, but it also means more expensive treatments, hospital stays and monitoring. If we can turn this on its head and find cancer at its earliest stages when it’s easier to treat, not only will we be able to save lives on a vast scale, but we will be saving our NHS millions of pounds that would otherwise be needed for costly late stage treatments.

"For the first time, the Roadmap shows us how we can bring together the entire research, commercial and health ecosystem to create a future where lives are not needlessly lost due to late diagnosis."

Terry Kavanagh, who was diagnosed with lung cancer and took part in the consultation said: "I still remember the surgeon’s words after waking from surgery to remove half of my left lung, "Well Terry, I’m satisfied we caught it early". It’s why I’m still here. Taking part in the roadmap really opened my eyes to the number of disciplines that have to come together in a bigger plan to help other cancer patients. Hopefully one day, early detection will be a reality for every cancer."

On October 5, 2020 Oasmia Pharmaceutical AB, an innovation-focused specialty pharmaceutical company, reported that Elevar Therapeutics, Inc. and Taiba Middle East FZ LLC have entered into an exclusive agreement under which Taiba will commercialize and distribute Apealea (micellar paclitaxel) in certain countries throughout the Middle East and North African (MENA) region (Press release, Oasmia, OCT 5, 2020, View Source [SID1234568100]). Under the terms of the agreement, Taiba will also be responsible for managing named-patient requests through which physicians can legally and ethically prescribe Apealea for patients prior to commercial availability.

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Apealea is a patented formulation of paclitaxel in combination with Oasmia’s proprietary XR-17 technology which encapsulates individual active pharmaceutical ingredients (APIs) in a layer of micelles, making the API and micelle formulation water soluble and therefore usable in water based intravenous injections.

Apealea has been approved by the European regulatory authorities for use in combination with carboplatin for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer.

In March 2020, Oasmia signed a global strategic partnership with Elevar Therapeutics for the commercialization of Apealea, making Oasmia eligible for potential milestone payments of up to USD 678 million- and double-digit royalties on sales.

François Martelet, M.D., CEO of Oasmia, commented: "It is great to see Elevar secure a quality regional partner for the MENA region which will initiate the process of obtaining regulatory approvals and commercialization. If regulatory approval is obtained, Apealea will be the first Cremophor-free formulation of paclitaxel approved for use in ovarian cancer in the Middle East and North Africa region and offer many cancer patients a therapeutic option with far less side effects."

Alex Kim, CEO of Elevar Therapeutics, added: "Partnering with Taiba in the Middle East and North Africa is an important milestone in our global registration and commercialization strategy for Apealea. This is the first regional partnership deal for Apealea, we are in active discussions with a number of other potential partners for other regions around the world and look forward to updating the public as these deals are executed."

On October 5, 2020 Guardant Health, Inc. (Nasdaq: GH). Despite advances in precision oncology, reported that progress is slowed by the limitations of tissue genotyping, which is traditionally used to enroll patients in clinical trials (Press release, Guardant Health, OCT 5, 2020, View Source [SID1234568116]). A new study published in Nature Medicine,1 led by the National Cancer Center Hospital East (NCCHE) in Japan, demonstrates that the Guardant360 liquid biopsy is not only concordant to tissue genotyping, but also accelerates clinical trial enrollment, detects more actionable alterations, and achieves similar treatment response rates and progression-free survival in patients with advanced gastrointestinal cancer. Publication link here.

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The study, SCRUM-Japan GOZILA, compares comprehensive genomic profiling using the Guardant360 liquid biopsy, versus tissue genotyping for trial enrollment into the SCRUM-Japan study network. Patients with advanced gastrointestinal cancer, including gastric and colorectal cancer, were matched to novel therapies that target the specific biomarkers identified. Compared to tissue genotyping (n=5,621) used in GI-SCREEN, the Guardant360 liquid biopsy (n=1,687) shortened screening duration by 67 percent (median 11 vs. 33 days) and improved trial enrollment rate by 132 percent (9.5 vs. 4.1 percent).

Additionally, the Guardant360 liquid biopsy revealed more actionable alterations because of its high success rate and ability to detect heterogeneously-distributed mutations which are often missed by single-locus tissue analysis. Most importantly, similar objective response rates and progression-free survival were seen in both studies, which included patients who were matched to interventional biomarker-targeted therapies when their cancer had progressed, after receiving first-line treatment.

"The data demonstrate that genomic profiling by ctDNA (circulating tumor DNA) analysis using the Guardant360 liquid biopsy has the advantage of shorter turnaround times and improved patient enrollment compared to tissue biopsy for clinical trials, without compromising treatment efficacy. The paradigm of precision oncology should be shifted toward greater use of liquid biopsies." said the Principal Investigator of this study Dr. Yoshiaki Nakamura, Attending Physician, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East.

AmirAli Talasaz, Ph.D., Guardant Health President added, "These data complement other studies supporting the routine use of the Guardant360 test in personalized treatment decisions for patients with advanced cancer, and its potential to significantly accelerate the development and delivery of innovation in precision medicine to patients."

The Guardant360 test is increasingly being used by pharmaceutical companies and academic researchers in clinical trials to accelerate precision medicine drug development, and by oncologists to guide treatment across solid cancers as the number of treatment-relevant genomic alterations continues to grow. Using next-generation sequencing, the Guardant360 test analyzes 74 genes using cell-free tumor DNA from blood samples and is broadly covered by Medicare for use across the vast majority of advanced solid tumors and many private payers. The Guardant360 CDx was recently approved by the FDA for tumor mutation profiling, also known as comprehensive genomic profiling (CGP), in patients with any solid malignant neoplasm (cancerous tumor). The Guardant360 CDx is also approved as a companion diagnostic to identify non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) alterations who may benefit from treatment with Tagrisso (osimertinib).

On October 5, 2020 Researchers at The University of Texas MD Anderson Cancer Center reported that have identified molecular and cellular characteristics of anti-CD19 CAR T cell infusion products associated with how patients with large B-cell lymphoma (LBCL) respond to treatment and develop side effects (Press release, MD Anderson, OCT 5, 2020, View Source [SID1234568101]).

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The research team also found that early changes in circulating tumor DNA one week after CAR T cell therapy may be predictive of treatment response in a particular patient. The paper was published online today in Nature Medicine.

"CAR T cell therapy is highly effective against LBCL," said corresponding author Michael Green, Ph.D., associate professor of Lymphoma and Myeloma. "However, we experience two main clinical challenges: achieving long-term remission and managing treatment-associated adverse events."

This study suggests that, within the first week of therapy, clinicians may be able to identify a subset of patients who may experience more poor outcomes or adverse treatment reactions, said Green. This would allow the care team to adjust therapy to improve efficacy or to act to mitigate toxicity.

CAR T cell signature, early molecular response may predict long-term outcomes

For this study, researchers performed single-cell analysis on CAR T cells to study gene expression profiles in the infused cells. CAR T cells were collected from those remaining in infusion bags following treatment of 24 patients with LBCL. These genetic profiles were compared to treatment responses, determined at three months post-infusion by PET/CT scan.

"When we look at the characteristics of the infused CAR T cells, we found that samples from patients who were less responsive to treatment had exhausted T cells, whereas those who experienced complete responses had T cells expressing ‘memory’ signatures," said co-corresponding author Sattva Neelapu, M.D., professor of Lymphoma and Myeloma. "Additionally, one cellular signature of T cell exhaustion was more commonly found in patients who exhibited a poor molecular response, and poor molecular response is generally associated with less-positive, long-term outcomes."

Further, the researchers analyzed early molecular responses in the patients by monitoring changes in circulating tumor DNA from treatment to one week post-infusion. The magnitude of change in tumor-associated DNA corresponded with response, suggesting that patients who displayed an early molecular response were more likely to experience a clinical response to treatment.

CAR T cell features predict likelihood of severe side effects

Adverse side effects of CAR T cell therapy can include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). These adverse events can delay patients’ recovery and can lead to increased need for hospitalization and intensive care.

"When we examined the infusion product, we found that a cell population with characteristics similar to myeloid cells, with a monocyte-like transcriptional signature, was associated with development of high-grade neurotoxicity," said Green. "Detecting these cells may subsequently lead us to identify patients who would be at higher risk of developing neurotoxicity, allowing us to provide prophylactic treatment with agents that target the specific cellular features."

Further examination may lead to insights into the types and attributes of the cells present within the CAR T infusion product.

"This study also tells us that some rare and unexpected cells identified by single-cell analysis could be biologically important," said co-corresponding author Linghua Wang, M.D., assistant professor of Genomic Medicine. "Going forward, we plan to functionally characterize these monocyte-like cells to better understand their specific biological mechanisms driving these clinical results."

These findings will help researchers develop clinical interventions that can block or target these cells. They also plan to validate the capacity of circulating tumor DNA to accurately predict patients’ long-term outcomes.

This research was supported in part by the B-cell Lymphoma Moon Shot, part of MD Anderson’s Moon Shots Program. With support from the Moon Shot and the Cancer Prevention & Research Institute of Texas (CPRIT), the research team plans to utilize PDX models of disease that relapsed following anti-CD19 CAR T cell therapy to preclinically test interventions that could lead to better treatment responses or to prevention of adverse side effects.

Other research support came from the Schweitzer Family Fund, the National Cancer Institute (P30 CA016672) and start-up research funds from MD Anderson. A full list of co-authors and their disclosures can be found here.