On July 16, 2020 Genmab A/S (Nasdaq: GMAB) reported that worldwide net sales of DARZALEX (daratumumab), including sales of the subcutaneous formulation, as reported by Johnson & Johnson were USD 901 million in the second quarter of 2020 (Press release, Genmab, JUL 16, 2020, View Source [SID1234561932]). Net trade sales were USD 492 million in the U.S. and USD 409 million in the rest of the world. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

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About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy2. Daratumumab is the first subcutaneous CD38-directed antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.3 DARZALEX FASPRO is the first subcutaneous CD38-directed antibody approved in the U.S. for the treatment of multiple myeloma.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,4,5,6,7

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

On July 16, 2020 Seventy-five organizations from around the world have endorsed the new Brain Tumour Patients’ Charter of Rights, a document intended to help initiate positive change in the care of people diagnosed with brain and central nervous system tumours (Press release, EORTC, JUL 16, 2020, View Source [SID1234561931]). The Charter provides a framework for the reduction of inequalities in care and the achievement of policy objectives aimed at improving healthcare systems and communications. It can also be used by individual patients to underpin particular aspects of their care. Ultimately, the goal of The Brain Tumour Patients’ Charter of Rights is to achieve the best possible health and quality of life for adults, children and adolescents living with brain tumors by encouraging and supporting quality standards, policies, and practices.

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"Patients have always been at the core of EORTC scientific strategy focusing on major public health needs in oncology. With rare tumours standing high on the scientific agenda, the standards of care in neuro-oncology has been a flagship programme at EORTC," said Dr Denis Lacombe, EORTC Director General. "This charter greatly contributes to the efficient implementation of therapeutic progress by giving patients important rights for access to research and state of the art care."

The Charter sets out the rights to which all brain tumour patients and caregivers should be entitled no matter where they live in the world.

"The Brain Tumour Patients’ Charter of Rights has worldwide relevance," said Kathy Oliver, Chair of the International Brain Tumour Alliance (IBTA) and one of the members of the Charter drafting group. "We’re excited that so many patient organizations and professional societies are supporting the Charter and we hope it will prompt productive discussion and debate and bring about positive change where necessary. The Charter is the result of a truly global collaborative process to help people who are diagnosed with this devastating disease, and those who care for them and treat them."

The Charter enumerates ten fundamental categories of "rights" for brain tumour patients that every country should strive to deliver:

Acknowledgment and Respect
Appropriate Investigation of Signs and Symptoms
A Clear, Comprehensive, Integrated Diagnosis
Appropriate Support
Excellent Treatment and High-Quality Follow-Up Care
The Care Relationship
Supportive/Palliative Care
Rehabilitation and Wellbeing
Medical Information and Privacy
Appropriate End-of-Life Options and Care
Within each category, specific policies, practices, and standards – a number of which will be aspirational in some countries – are defined.

The Brain Tumour Patients’ Charter of Rights was developed through a multi-stakeholder and iterative process and is a "living document", subject to annual review.

ABOUT BRAIN TUMOURS

There are over 100 histologically distinct types of primary brain and central nervous system (CNS) tumours, each with its own spectrum of clinical presentations, treatments, and outcomes. [1]
Brain and CNS tumours can affect anyone of any age – from very young babies, children and adolescents to young adults, older adults and the elderly.
Brain and CNS tumours are responsible for substantial symptoms, side effects and mortality worldwide.
The worldwide incidence rate of primary malignantbrain and other CNS tumours in 2018, age-adjusted using the world standard population, was 3.5 per 100,000. Incidence rates by sex were 3.9 per 100,000 in males and 3.1 per 100,000 in females. This represented an estimated 162,534 males and 134,317 females who were diagnosed worldwide with a primary malignant brain tumour in 2018, an overall total of 296,851 individuals. [2]
In the United States, brain tumours kill more children under 15 years than any other cancer. [1]
In 2016, malignant brain and CNS tumours were responsible for 227,000 deaths globally with an age-standardised death rate of 3.24 per 100,000 person-years. [3]
Central Brain Tumour Registry of the United States (CBTRUS) Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012–2016, View Source
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68(6):394–424. View Source View Source.
The Lancet Neurology, https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30468-X/fulltext

On July 15, 2020 Cancer Research UK reported that it has developed plans to become a leaner, more focused organisation following the devastating impact of COVID-19 on its fundraising income (Press release, Cancer Research UK, JUL 15, 2020, View Source [SID1234562078]). The charity is making difficult decisions to significantly reduce how much it spends on beating cancer, its operations and the number of staff following an anticipated £300 million decline in fundraising income over the next three years, but is more focussed than ever on staying at the forefront of the global fight against cancer.

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The charity plans to rebuild, adapting to the changed world and finding new opportunities, in order to continue to make an impact for people with cancer. There will be a continued focus on world-class research and shaping the UK’s science ecosystem, and a commitment to influencing and providing excellent information across cancer prevention, diagnosis and treatment.

Read more from Cancer Research UK’s chief executive Michelle Mitchell on plans to rebuild and adapt.
But due to the projected drop in income, of £160 million this year (30%) and £300 million over three years, the charity needs to make tough choices about where and how it spends its money. There will be a greater focus on investing strategically for the future, whilst contracting in other areas amidst continued financial uncertainty.

Regrettably, Cancer Research UK will have to stop some programmes of work, reduce the amount or scope of other activities, and will be reducing the size of its workforce by 500 roles (circa. 24%), not including trading. The recruitment freeze that was put in place as an early response to COVID-19 will reduce the impact on existing staff, but sadly the charity expects to make 295-345 redundancies (14-17%) not including trading, within six months.

The charity also recently announced unavoidable cuts to its life-saving research. It plans to introduce a new research model designed to maximise impact from a lower level of spend, and will reduce its research spend to £250 million within four to five years – a cut of £150m from what the charity had planned to spend. But Cancer Research UK is doing everything it can to find more financial support, and is calling on the Government to help find a solution to this funding gap. The transition to a new funding model will be phased carefully to minimise the impact on the research community and existing portfolio. The commitment to maximising research impact remains, and the charity will continue to back the best researchers around the world.

The plan also outlines how Cancer Research UK will be more focused than it has ever been – doing less, but maintaining the highest quality in its work. It will deepen relationships with its supporters, so that thanks to their generosity it can return to growth as quickly as possible. The charity will continue to invest in digital transformation, basing its approach on how supporters want to engage, and will reach out to philanthropic individuals and organisations around the world to support its work.

Michelle Mitchell, chief executive at Cancer Research UK said: "We’re living through a global crisis unlike any other and, as it’s unfolded, it’s become clear that there’ll be a huge economic impact for years to come. As the world’s leading cancer charity dedicated to saving lives through research, we must always focus on delivering our pioneering work into the prevention, diagnosis and treatment of cancer.

"We made some very difficult decisions early on to mitigate the impact on our work; we moved all of our staff to 80% pay, furloughed 60% of staff, and cut £44 million from our research. But it is with a heavy heart that I can confirm we will have to reduce the size of our workforce, and make significant cuts to our research spend, as a result of the situation we find ourselves in. With such a significant shortfall in income, we cannot afford to keep spending at the same levels. But that doesn’t make those decisions any easier. We’re keeping our dedicated, hard-working staff up to date on developments as we have them, and their professionalism throughout this period has been hugely appreciated.

"I am confident that through our world-leading research, information and influencing, we will continue to make transformative steps in the prevention, diagnosis and treatment of cancer. This plan sets the direction for a new phase in the life of Cancer Research UK and will help us respond to the changed world, quicker than we’ve ever done before. We will emerge a streamlined charity, but still with a resolute drive for impact. Together, we will still beat cancer and realise our ambition to improve cancer survival to 3 in 4 by 2034."

Cancer Research UK remains committed to ensuring at least 80p in every £1 raised is available to spend on beating cancer.

On July 15, 2020 A Ludwig Cancer Research study reported that it has dissected how radiotherapy alters the behavior of immune cells known as macrophages found in glioblastoma (GBM) tumors and shown how these cells might be reprogrammed with an existing drug to suppress the invariable recurrence of the aggressive brain cancer (Press release, Ludwig Institute For Cancer Research, JUL 15, 2020, View Source [SID1234562070]).

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Led by Ludwig Lausanne Member Johanna Joyce and published in the current issue of Science Translational Medicine, the study details how radiotherapy dynamically alters gene expression programs in two subtypes of tumor-associated macrophages (TAMs) and describes how those changes push TAMs into a state in which they aid therapeutic resistance and growth. Joyce and her colleagues, led by first author Leila Akkari, now at the Netherlands Cancer Institute, also demonstrate that combining radiotherapy with daily dosing of a drug that targets macrophages—an inhibitor of the colony stimulating factor-1 receptor (CSF-1R)—reverses that transformation and dramatically extends survival in mouse models of GBM.

"What these preclinical data tell us is that for patients receiving radiotherapy for glioblastoma, adding CSF-1R inhibition to the treatment regimen could have the effect of prolonging survival," says Joyce.

GBM patients typically survive little more than a year following diagnosis, as the cancer inevitably recurs and typically resists multiple therapies. But it was not known whether TAMs—which are linked to cancer cell survival and drug resistance in a variety of tumor types—promote GBM resistance to ionizing radiation, which is part of the standard of care for the aggressive tumor.

Two types of macrophages populate glioma tumors. One is the brain’s resident macrophage, or microglia (MG). The other is the monocyte-derived macrophage (MDM) that patrols the body, gobbling up pathogens and dead cells, or their detritus, and initiating additional immune responses. Macrophages can, however, be pushed into an alternative state—often termed the M2-like activation phenotype—in which they aid tissue healing rather than respond to threats. Many cancers coax macrophages into this alternative phenotype, which supports tumor survival and growth.

Joyce and her team found both MG and MDMs flood into GBM tumors in mice to clean up the cellular detritus following an initial course of radiotherapy. But when the gliomas recur, interestingly, it is MDMs that predominate in the TAM populations. The gene expression profiles of these MDMs in irradiated tumors, however, more closely resembles those of MG. They found, moreover, that both MDMs and MG in irradiated gliomas are alternatively activated into a wound-healing phenotype and secrete factors that bolster DNA repair in cells.

"Not only were these macrophage populations changing but, more importantly, they were now able to interfere with the efficacy of radiotherapy because they could help cancer cells repair the DNA damage it causes," explains Joyce.

"So you have this yin/yang situation. The irradiation is of course destroying many of the cancer cells, but it has also caused all these macrophages to rush into the tumor to clean up the mess and, as a consequence, they’ve been super-activated to create a permissive niche for the remaining cancer cells to form new tumors."

To see if depleting MDMs specifically might reverse that effect, the researchers treated different GBM mouse models with an antibody that blocks the entry of MDMs into the brain. But that only nominally improved survival in one of the models.

The Joyce lab has previously reported that TAMs can be pushed out of the wound-healing phenotype by CSF-1R inhibitors, so they next tested whether that strategy might bolster the efficacy of radiotherapy.

They found that a single, 12-day cycle of CSF-1R inhibitor treatment following radiotherapy enhanced the initial therapeutic response and extended the median survival of mice by about three weeks beyond the modest increase seen with radiotherapy alone. By contrast, a continuous, daily regimen of CSF-1R inhibition for several months following radiotherapy yielded the most striking results, reprogramming TAMs and dramatically extending median survival.

"We had approximately 95% of mice survive the full course of this six-month study," says Joyce. In addition, mice engrafted with patient-derived tumors showed increased survival.

Joyce and colleagues are further exploring the mechanism by which TAMs promote DNA repair and otherwise assist cancer cell survival in GBM.

This study was supported by Ludwig Cancer Research, the Swiss Cancer League, the Dutch Cancer Society, the Dutch Research Council, The Brain Tumor Charity, the Brain Tumor Funders Collaborative, the American Brain Tumor Association and the U.S. National Cancer Institute.

In addition to her post as a Member of the Ludwig Institute for Cancer Research, Lausanne Branch, Joyce is also a Professor at the University of Lausanne.

On July 15, 2020 Aspen (APNJ.J) reported that it has offered to cut prices by an average of 73% for six off-patent cancer drugs, EU antitrust regulators said on Tuesday, a move that could help the South African pharmaceutical company avoid a potentially hefty fine (Press release, Aspen Global, JUL 15, 2020, View Source [SID1234562069]).

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The European Commission opened an investigation into Aspen in 2017 following concerns it may have charged excessive prices for drugs critical in treating patients suffering from certain types of life-threatening cancer, such as leukaemia and multiple myeloma.

Aspen’s price cuts will cover all of Europe except for Italy, which imposed a five million euro ($5.68 million) fine on the company in 2016 for price hikes of up to 1,500% for some drugs.

The European Commission, the EU executive, said it would seek feedback from interested parties before deciding whether to accept the company’s offer.

"The proposed commitments aim at bringing to an end Aspen’s suspected excessive pricing conduct with respect to its six off-patent cancer medicines, which the Commission suspects to constitute an abuse of a dominant position," the Commission said in a statement.

It said Aspen’s proposal would lead to an immediate price cut in its net prices to below 2012 levels for most of the drugs, guarantee supply and involve a 10-year price ceiling.

The price cuts would apply retroactively from Oct. 1, 2019, when Aspen first submitted its concessions to regulators.

Under its antitrust settlement procedures, accepting the offer would mean no fines and no acknowledgement of wrongdoing. Sanctions can amount to 10% of a company’s global turnover.