Oncology Highlights - July 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
Breakthrough – fat fuels brain cancer growth
For decades, scientists have been focusing on ways to starve cancer cells of their sugar supply, but now a new study published in the journal Neuro-Oncology has found evidence in mice experiments that a common form of cancerous brain tumours use fat as their preferred source of energy. The glioma tumours in mice were treated with a fatty acid oxidation inhibitor called etomoxir which blocks the cells’ ability to process fat as fuel. This slowed down the cancer’s growth resulting in a "prolonged median survival time” by 17 percent. This discovery brought forth an entirely new approach how to treat brain tumours. Gliomas, such as astrocytoma or ependymoma, belong to the hardest cancers to treat with 60 percent of patients that die within one year. Read more >
1 in 12 cancer patients suffer from a secondary, unrelated malignancy
A recent study performed by researchers at the University of California in Los Angeles (UCLA) looking at long-term outcomes in cancer patients found that 8 percent of patients - or one in 12 - already diagnosed with one form of cancer end up developing other, unrelated secondary cancers, especially lung cancer. The current study included more than 2 million people diagnosed with cancer. Out of the patients that developed a secondary tumor, a 13 percent died of their primary tumor and 55 percent of their secondary tumour. The research team found that patients diagnosed with bladder cancer were the most at risk for developing a second cancer. Therefore, the findings point to the need for annual screening with a CT scan of the lungs for bladder cancer patients, for broader monitoring of cancer survivors, and a new routine of long term follow-up for cancer patients. Read more >
Diet and exercises reduce cancer-promoting protein levels
A study, published in the journal Cancer Research suggest that simple changes to the lifestyle - maintaining a healthy diet and exercising frequently - could reduce the amount of blood proteins in healthy humans that are involved in angiogenesis and in general would promote the development and survival of malignant cells. The study investigated 439 women suffering from overweight and/or obese during their diet and exercise period and it was found that women experiencing weight loss had a decline in levels of blood proteins associated with angiogenesis. A linear trend was seen in the reduction, revealing the higher the amount of weight loss the women experienced, the greater was the reduction in cancer-promoting protein levels. Researcher Catherine Duggan noted that reducing the circulating levels of antigenic factors through weight loss, might be associated with a less favourable milieu for tumour growth and proliferation but the direct impact on tumour growth for example in cancer patients remains to be shown. She concludes that making small lifestyle changes to reduce weight will lower the risk factors for cancer. Read more >
Alcohol causes 7 types of cancer
The study, published in the scientific journal Addiction, concludes that alcohol can cause seven forms of cancer. The review from the University of Otago in New Zealand aimed to summarise data from published biological and epidemiological research to evaluate the strength of evidence that alcohol causes cancer. The researcher was able to link alcohol to cancer of the mouth, throat, larynx, oesophagus, liver, colon, rectum and female breast but most likely to other cancers as well. Even though scientists are unsure of the exact biological reasons why alcohol causes cancer there is strong evidence of a direct, harmful effect of drinking with the highest risks for heavy drinking. Though, this study suggested even people who drink at low or moderate levels may contribute to a significant proportion of cancer cases. The study also states there is no suggestion of a "safe" level of drinking with respect to cancer. Read more >
Drinking alcohol regularly can increase the risk of at least 7 different cancers.
(Source: Cancer Research UK)
FDA put CAR-T cell trial on hold after 3 participants’ deaths
A CAR-T advanced program in Phase II known as ROCKET trial from Juno Therapeutics was recently suspended by the FDA after 3 deaths, which appear to be treatment-related. This trial studied the effect of Juno’s candidate JCAR015 in 90 adult patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (ALL). All three deaths were in young patients, all under the age of 25, having received fludarabine as part of the preconditioning regimen, and all three died from cerebral oedema. The preconditioning regimen consisted of cyclophosphamide plus fludarabine over three days. The latter has a history of eliciting neurotoxicity, therefore Juno said it suspects the fludarabine preconditioning regimen causing the problems and has proposed to the FDA that it continue the ROCKET trial using JCAR015 with cyclophosphamide preconditioning only. The majority of patients treated in the trial received preconditioning with cyclophosphamide alone. No treatment related deaths occurred in those receiving cyclophosphamide alone, and neurotoxicity was within the range of expectations. Now Juno Therapeutics hopes to get permission from the US Food and Drug Administration to continue the CAR-T trial without Fludarabine. Read more >
U.S. Patent Office Pilot Program for Cancer Immunotherapy
The United States Patent and Trademark Office (USPTO) announced the implementation of a fast-track pilot program named Cancer Immunotherapy Pilot Program (CIPP). The new program offers applications relating to cancer immunotherapy a faster review of the patent with the objective to complete examination of an application within 12 months or less. In case the application qualifies for CIPP it will provide the “accelerated or prioritized examination program” for free to this particular cancer immunotherapy patent application. Usually, patent applications are examined by the USPTO in the order of their U.S. filing date. The examination process, from the filing date to a final statement can take about three years. The USPTO’s “accelerated or prioritized examination program” usually requires the applicant either to provide extensive examination support documents or pay considerable fees (up to $4,000). The program will run for one year, but may be extended. Currently the USPTO deal with circa 900 cancer immunotherapy-related patent applications per year. Thus, the pilot program is being initiated with the aim of boosting the applicant’s prospects for cancer immunotherapy treatments. Read more >
EMA calls for suspension of drugs tested by Indian CRO Semler Research Centre
The European Medicines Agency (EMA) has recommended suspending a number of nationally approved medicines associated with the Indian based CRO named Semler Research Centre but also has stopped the current evaluation for authorisation of medicines for which bioequivalence studies were conducted by this CRO. The quality of the bioequivalence studies performed by Semler Research Centre is being called into question after the CRO has been subject to a recent GCP inspection by the WHO and FDA. Critical findings and deficiencies were identified, including the substitution and manipulation of samples. National authorities of EU member state can temporarily postpone the suspension in the interest of patients due to e.g. lack of available alternatives. A list of medicines recommended for suspension is available on the EMA web page. Read more >
EMA / FDA
EMA oncology drug recommendations for approval July 2016:
The Committee for Medicinal Products for Human Use (CHMP) adopted a position opinion for:
- an extension of the indication for the medicinal product:
Idelalisib (Zydelig®, Gilead Sciences International) is indicated in combination with an anti‑CD20 monoclonal antibody (rituximab or ofatumumab) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL): who have received at least one prior therapy, or as first line treatment in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies. Zydelig is also indicated as monotherapy for the treatment of adult patients with follicular lymphoma (FL) that is refractory to two prior lines of treatment. The drug is a chemotherapy blocking the delta isoform of the enzyme phosphoinositide 3-kinase, thereby inducing apoptosis in tumor cells and preventing proliferation of the latter.
- a change to the terms of the marketing authorisation for the medicinal products:
Crizotinib (Xalkori®, Pfizer) is indicated for the first-line treatment of adults with anaplastic lymphoma kinase (ALK)‑positive advanced non-small cell lung cancer (NSCLC). Crizotinib functions as a protein kinase inhibitor and blocks the constitutive kinase activity of the EML4-ALK fusion protein which is present in abnormal anaplastic lymphoma kinase positive patients.
Ibrutinib (Imbruvica ®, Janssen-Cilag International) as a single agent is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). Imbruvica as a single agent is also indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). As a single agent or in combination with bendamustine and rituximab (BR) it is indicated for the treatment of adult patients with CLL who have received at least one prior therapy. Imbruvica as a single agent is indicated as well for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo‑immunotherapy. The drug is an inhibitor of the enzyme Bruton's tyrosine kinase and by this means blocks B cell receptor signalling, which drives cells into apoptosis.
FDA Issuing Two Draft Guidances on NGS-Based Tests
Supporting the US President’s Precision Medicine Initiative, the US Food and Drug Administration (FDA) issued on 6 July 2016 two draft guidances which shall assure a flexible and streamlined approach to the oversight of next generation sequencing (NGS) diagnostic tests. These test either have the potential to detect medically important differences in the genomics of a subject or the subject’s DNA can be scanned for genomic variations in order to detect potential disease risks. The objective of these guidelines is to offer a flexible and adaptive regulatory oversight of these tests, allowing for variations in the way companies develop and validate the new technologies. The first draft guidance, named "Use of Standards in FDA’s Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases" gives recommendations for NGS-based tests for rare hereditary diseases. The second draft guidance titled “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics” proposes an approach for test developers to rely on data and assertions from FDA-recognized public genome databases to support clinical claims for their tests. The FDA is hoping for comments and valuable input on both draft guidances. Read more >
EMA seeks to revise guidance on Phase I first-in-human clinical trials
The European Medicines Agency (EMA) is proposing changes to the current guidelines on first-in-human clinical trials to improve risk-based strategies. This proposal was made with cooperation from the European Commission and the Member States of the European Union (EU) and addresses the increased complexity of the protocols of first-in-human clinical trials. EMA launched a public consultation on 21 July 2016 wherein these changes are outlined in a new concept paper. The concept paper and the comments received will be used for an update of the guideline and a draft revised guideline is expected to be published before the end of 2016 for consultation. Read more >
Logo European Medicines Agency (EMA) (Source: EMA)