Oncology Highlights - May 2016
Reading our newsletter will only take a few minutes and allows you to keep up to date with last month’s news items on oncology drug development.
Kind regards, the SMS-oncology team
Genomic research reveals ten novel subgroups in breast cancer
Experts at Cambridge University, UK did a reanalysis of 173 sequenced genes in 2,433 samples of primary breast cancer patients from the METABRIC study and found 40 gene mutations driving progression of the disease. Interestingly, several of these mutated genes were not related to breast cancer so far. Mapping of the ‘genetic blueprints for breast cancer' resulted in the classification of 10 distinct subgroups of breast cancer. The information gained from this research might help in several different ways: For example, one of the major findings regarding the mutations was the linkage of the more commonly mutated PIK3CA to poor survival within three of the ten subgroups of breast cancer. In the future this may help identifying in which cases treatment with PIK3CA targeting drugs is reasonable and in which cases it is not. The study published in Nature Communications highlights once again how complicated cancers are and that overall genomic research like this can refine treatment for breast cancer patients in the future. Read more >
T cells use “handshake” to distinguish between friend and foe - new mechanism insights for T cell activation
A group of scientists led by Khalid Salaita, published a study with new insights on the specific activation process of T cells against harmful cells. T cells can recognize specific antigenic peptides on the cell surface of antigen presenting cells (APC), identifying peptides as derived from either harmless or harming cells. Khalid’s group focused on mechanical forces of cellular processes as they hypothesized that mechanical strain might also play a role in T cell responses. By examining the interaction between the T cell receptor (TCR) of T cells and the ligand on the surface of APCs, they discovered that T cells give a very specific and finely tuned mechanical tug (or “handshake”) to determine whether it is a friend or foe. The TCR pulls at the ligand and if the tug releases easily, it indicates a friend (harmless ligand), whereas a strong resistance to this pulling indicates a foe (harming ligand), which consequently activates the immune response. These novel findings could have major impact on improving several of the T cell dependent cancer therapies. Read more >
Colorectal cancer patients might benefit from being overweight
In a new observational study published in JAMA Oncology, evidence was found that overweight colorectal cancer (CRC) patients are likely to have better survival rates than patients with normal weight. Until now overweight has been mostly identified as a factor that increases the risk of several diseases, especially cancers. Author Candyce Kroenke and her team did research on 3,400 patients who were diagnosed with stage I-III CRC between 2006 and 2011 and compared their risk of death over a time period of 15 months from diagnosis. It was found that overweight patients had a 55% less risk of dying from their cancer burden, supporting the “obesity paradox”. Researchers highlighted that this study does not give evidence that overweight caused the decreased risk of death; it’s just an observation and everyone should keep in mind that in most cancers overweight persons develop cancer at higher rates. However, it does show that an advice on reduction of weight for a better health condition might not always be correct. So cookie, anyone? Read more >
Arsenic drinking water potential explanation for elevated bladder cancer risk in New England
In northern New England the bladder cancer mortality rates have been 20% above average compared to the United States overall for at least five decades. In order to find the reason for this elevated rates, researchers compared in defined geographic areas several risk factors of 1,213 people newly diagnosed with bladder cancer to 1,418 disease-free people. Arsenic as a cause of bladder cancer has already been proven in earlier studies and therefore researchers hypothesized for an association to arsenic in drinking water. With a high degree of certainty, the former wide-spread practice of water consumption from private wells (particularly dug wells) in the investigated areas could be associated with a higher probability of arsenic consumption and the consequent increased bladder cancer risk. The shallow dug wells seem to be potentially susceptible to contamination of arsenic-based pesticides used prior to the 1960s.The conclusion of the study was that low-to-moderate levels of arsenic in drinking water might be an explanation for the increased risk for bladder cancer in New England. Read more >
AbbVie to acquire startup Stemcentrx investing up to $10 billion
AbbVie has announced to acquire startup Stemcentrx for $9.8 billion, of which $5.8 billion to be paid up-front and up to another $4 billion in milestones. Not only will this be one of the largest biotech acquisitions in recent memory, it would also be one of the biggest private venture capital-backed acquisitions ever. Abbvie’s new investment might be associated with the expiring patent of Humira in December this year, their monocloncal antibody for the treatment of arthritis and psoriasis that belongs to the group of world’s top-selling drugs. Stemcentrx now offers the chance for the marketing of a new top-selling antibody candidate with its objective to treat cancer by eliminating cancer stem cells (CSCs). These cells are believed to give rise to the variety of cancerous cell types found within a particular cancer. Stemcentrx’s approach aims to kill these cancer stem cells in order to stop cancer at its beginning and thus prevent a new tumour development from the same CSCs. The company currently has five drug candidates in ongoing clinical trials, each specifically targeting the CSCs that are in control of the respective tumor. The furthest along and with encouraging results is Rovalpituzumab tesirine (Rova-T), a biomarker-specific antibody drug conjugate targeting the cancer stem cell protein DLL3 of small cell lung cancer. Read more >
Business unit of Novartis divided in 2: Novartis Pharmaceuticals and Novartis Oncology
Novartis reorganizes its main Pharmaceuticals business dividing it into two units: Novartis Pharmaceuticals and Novartis Oncology. This division shall bring more transparency into corresponding investments, in particular for the oncology drug development which is most popular with investors. Giving oncology its own department within Novartis shows how important cancer treatment is to Novartis’ future, especially after Novartis acquired GlaxoSmithKline’s oncology assets. Several personnel changes within Novartis have been mentioned as well. Paul Hudson will becomethe new CEO of Novartis Pharmaceuticals, thereby replacing current Division Head and CEO David Epstein who is going to leave the company, whereasBruno Strigini will be appointed CEO of Novartis Oncology. Both Hudson and Strigini will report directly to Joseph Jimenez, CEO of Novartis. Read more >
EMA / FDA
EMA oncology drug recommendations for approval May 2016:
The Committee for Medicinal Products for Human Use (CHMP) adopted a position opinion for:
- Carfilzomib (Kyprolis®, Amgen Europe) in combination with either lenalidomide and dexamethasone or dexamethasone alone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Carfilzomib is a proteasome inhibitor. The inhibition of the proteasome leads to an accumulation of poly-ubiquinated proteins within the tumour cell leading to apoptosis, which stops tumour growth.
CHMP also adopted an extension or adaptation of indication for:
- Brentuximab vedotin (Adcetris®, Takeda Pharma) for the treatment of adult patients with CD30+ Hodgkin lymphoma (HL) at increased risk of relapse or progression following autologous stem cell transplantation. Brentuximab vedotin is a CD30 specific monoclonal antibody conjugated to the antimitotic compound Vedotin. Adcetris has already an indication for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).
- Atezolizumab (Tecentriq®, Genentech ) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Tecentriq belongs to the promising class of PD-L1 inhibitors. The antibody will be used for the treatment of bladder cancer, for which no significant new medicines have been marketed in years.
- Nivolumab (Opdivo®, Bristol-Myers Squibb) for the treatment of patients with classical Hodgkin lymphoma (cHL) that have relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (Adcetris). Nivolumab is an anti-PD-1 antibody - a checkpoint inhibitor - blocking the inactivation of T cells that are capable of attacking the cancer. It is already approved for the treatment of melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC).
- Lenvatinib (Lenvima ®, Eisai) in combination with everolimus, for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy. Lenvatinib belongs to the group of vascular endothelial growth factor receptor (VEGFR) inhibitors and mainly targets VEGFR1/2/3 within the cancerogenic signal transduction pathway but also inhibits several other proteins that are part of this pathway. It is taken in form of capsules and in 2015 Lenvatinib was already approved for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.
EMA plans to improve safety of first-in-human clinical trials
EMA initiated an EU-wide review of first-in-human clinical trial guidelines. This follows the death of a healthy volunteer and the hospitalization of five others in a phase I trial in France earlier this year. A concept paper is expected in July identifying the areas for change and proposals to further minimize risk. The review is performed by two expert groups, one focusing on the preclinical data needed to initiate a trial in humans and the second group is looking at trial design to better ensure safety of the participants. The EMA also provided an interesting statistic, since 2005 a total of 14.700 phase I (305.000 subjects) have been conducted in the EU. Thus far only two severe incidents have been reported, namely the recent incidence in France and the TeGenero incident. Read more >
European initiative to protect healthcare professionals from occupational exposure to cytotoxic drugs
With increasing incidences in cancer and rising numbers of diseases that are treated by cytotoxic drugs, the exposure of health care professionals to these drugs immensely and continuously grows. Cytotoxic drug substances can cause severe health defects and are therefore classified as hazardous. But until now there is no official guideline or legislation within the European countries in order to keep these healthcare professionals (nurses, pharmacists and pharmacy technicians) save, even though they are at the highest risk of exposure. Finally, last year in November the European Parliament started with a first step to establish a safer cytotoxic drug associated work environment with a recommendations paper to initiate the way to legislation. The authors of this paper endorse a European legislation, give advice on preventive actions and recommend continuous education on safe handling of hazardous drugs by the healthcare staff. Moreover, a common definition was demanded for ‘Closed System Drug Transfer Devices’ – which are considered the best solution to safe handling, while some of the established cytotoxic drug containers that claim to be ‘Closed’ at present might produce aerosols, vapors and dripping – with a given detailed specification. Contributors to these recommendations now hope for a rapid establishment of EU wide standards for the conduct of occupational contact with cytotoxic drugs. Read more >