Oncology Highlights - August 2017
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!
The SMS-oncology team
Genes essential for cancer immunotherapy identified
A new study has identified genes that are necessary in cancer cells for immunotherapy to work, a treatment that sometimes causes a great response, while other patients don’t respond to the therapy at all. Immunotherapy relies on the destruction of cancer cells by T lymphocytes. However, somatic gene mutations can alter the vulnerability of cancer cells to the attack of T cells. To investigate which genes are involved, scientists knocked out every known protein-encoding gene of the human genome in a melanoma tumor cell line. The gene-modified cancer cells were tested how to respond to T cells, leading to a group of more than 100 genes that might play a role facilitating T cell tumor destruction. Next, these genes were examined on cytolytic activity, resulting in a final number of genes identified as necessary for cancer cells to respond to T cells. These results could serve as a blueprint to study the emergence of tumor resistance to T cell-based cancer therapies, and if validated in clinical trials this data could lead to improved immunotherapies. The study was published in Nature.
Colorectal Cancer mortality rates rises in adults under 55
Death amongst colorectal cancer (CRC) patients under 55 have been rising since 2004. Scientists analyzed over 240 thousand people who died from CRC between 1970 and 2014. Though a drop was seen from 6.3 per 100.000 in 1970 to 3.9 per 100.00 patients in 2004, this number has been rising for the 10 following years up to 4.3 per 100.000 – a rise of approximately 1 % per year. Interestingly, rates declined in black individuals in every age group. The results were particularly unexpected, as new screening methods prevents cancer and leads to earlier detection when cure rates are better. Though risk of CRC remains relatively low for young and middle-aged adults, this rise suggests that the increased incidence is not only due to earlier detection, but an actual escalation in disease occurrence. These results highlight the need for new interventions to improve use of age-appropriate screening and timely follow-up of symptoms. The study was published in The Journal of the American Medical Association.
United States Senate passes legislation to improve paediatric cancer drugs
On August 3rd, the United States Senate have passed a legislation that requires pharmaceutical companies to spend more resources on treatments for childhood cancers. In the last 20, years only 3 new cancer treatments have been approved by the FDA, in comparison to 190 in adults. For adults many breakthrough treatments have become available, both with better results and less harmful effects. At this moment, these treatments are not available for children though they show promising results. Previously, drug companies had the free choice to pursue paediatric cancers treatments, but with this new law the pharmaceutical companies are obliged to move forward. The legislation is now waiting to be signed by President Trump.
New potential tracer for better prostate cancer imaging
Researchers at the University of Michigan demonstrated the potential of a new PET tracer for imaging prostate cancer using Carbon-11 labeled sarcosine (11C-sarcosine). Prostate cancer has the second highest mortality amongst men, and sarcosine plays an important role in the progression and severity of the disease. The amino acid – also known as N-methylglycine – enters cells via proton-coupled amino acid transporters (PAT). These PATs are overexpressed in specific tissues and solid tumors. This possibly makes sarcosine a suitable imaging target, both for the monitoring of prostrate as well as other types of malignancy. Preclinical models showed tumor-to-background ratios obtained from 11C-sarcosine PET to be significantly elevated compared to 11C-choline, the currently used tracer for imaging prostate cancer. The new tracer is now being further developed for clinical use. The study was published in The Journal of Nuclear Medicine.
Kite Pharma acquired for $11.9 billion
Biopharmaceutical giant Gilead Sciences acquired Kite Pharma for $180.00 per share in cash, a 29% premium over the Friday closing price, which values Kite at approximately $11.9 billion. Hereafter, Gilead’s shares rose about 1% to $74.69. Kite Pharma was founded in 2009 and went public in 2014, and is one of the leaders in cell therapy development. Axicabtagene ciloleucel, one of their most advanced therapy candidates, is expected to be the first for the treatment of refractory aggressive non-Hodgkin lymphoma, which includes diffuse large B-cell lymphoma, transformed follicular lymphoma and primary mediastinal B-cell lymphoma, and is currently under review by the U.S. Food and Drug Administration.
No Committee for Medicinal Products for Human Use (CHMP) meeting was held in August.
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- Nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of patients 12 years and older with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic colorectal cancer, that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
- Enasidenib (Idhifa, Celgene) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by the simultaneously approved companion diagnostic RealTime IDH2 Assay, for the detection of the IDH2 mutation.
- A liposome-encapsulated combination of daunorubicin and cytarabine (Vyxeos, Jazz Pharmaceuticals) for the treatment of adults with newly-diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC), two types of AML with a poor prognosis.
- Inotuzumab ozogamicin (Besponsa, Wyeth) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The CD22-directed antibody-drug conjugate (ADC) was already approved by the EMA earlier in 2017.
- Olaparib tablets (Lynparza, AstraZeneca) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. The PARP inhibitor was already approved as 4th line (or later) treatment of Advanced gBRCA-mutated ovarian cancer.
- Tisagenlecleucel (Kymriah, Novartis) for the treatment of patients up to age 25 years with B-cell precursor ALL that is refractory or in second or later relapse. The CAR-T cell therapy is the first FDA-approved gene therapy in the United States.