Oncology Highlights - March 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.
Kind regards, the SMS-oncology team
New successful approach for detecting cancer with blood test
Researchers from the University of California San Diego have developed a blood test to both detect cancer and locate where in the body a tumor is growing. Current blood tests use the conventional approach of screening DNA released by dying tumor cells. Those approaches indicate if there is tumor growth in patients, but don’t indicate where that tumor resides. With this new method, CpG methylation haplotypes are utilized to detect the location. Tumor cells compete with normal cells for nutrients and space, killing the healthy cells and releasing their DNA. This DNA has unique signature CpG methylation haplotypes which can be used to determine the corresponding tissue. Using signals from other cells instead of cancer cells, the researchers realized that both sets of signals can be integrated to both determine the presence/absence of a tumor and where the tumor is growing. Though proof of concept has been shown, clinical development is needed to further optimize and refine the new method. The study was published in Nature Genetics.
Genome-wide association study identifies genetic errors related to gliomas
An international team of researchers have identified 13 new genetic errors that are related to a high risk of glioma. With a 5-year survival of 34.4%, brains tumors are a difficult cancer type to treat. Of all brain tumors, gliomas account for 27% and have a yearly incidence of 3-5/100,000 with a slight predominance in males, causing 13,000 deaths a year in the US. Patients diagnosed with glioblastomas have a survival rate of only 5%. With the current meta-analysis of 12,500 glioma patients and 18,000 healthy controls, the researchers now doubled the number of known genetic disorders raising the risk of brain cancers. The study shows genetic errors that impact several cell functions such as genesis and division of neurons, cell cycle regulation, DNA repair and protein production. Besides the newly discovered errors, the study confirmed the role of previously identified genes. Understanding the genetics of glioma in such detail allows clinicians to identify people with high inherited risk, and opens a search for new treatments. The study was published in Nature Genetics.
The phase II clinical trial for JCAR015, intended for the treatment of Acute Lymphoblastic Leukemia (ALL) in adults, has permanently stopped. Three months earlier, the study was put on hold as a result of patient deaths. In 2016, the drug was already put on hold two times. The first time Juno blamed two deaths to the additional drug fludarabine. Removing the chemotherapeutic compound, the trial continued but was halted again later in November, when two more patients died from cerebral edema. It is now unknown if the trial will be canceled, modified or continues with the same course. More information will be available after the investor conference in December 2017. The company now intends to start a different trial to treat adult ALL in 2018 that is more similar to its JCAR017 trial, which tests pediatric ALL and has no deaths in the 43 included patients. Juno Therapeutics’ stock dropped 5.3 % just hours after the news was announced.
Japan follows US in fighting drug prices
Where Trump started his mission to reverse drug prices in the US, Japan is now taking a similar track. In Japan, $93 billion is annually spent on medication with a coverage of 40% by the government. Last December, plans were announced to review drug prices more frequently. Prices of Opdivo were halved in the last few months, following by a cut of 32% for Sovaldi this April, and many more are expected to follow. Researchers estimate sales in the world’s third-largest drug market (after the US and China) will drop with 30% to about $62 billion through 2025. Experts claim Japan risks multinationals will redirect their investments in drug development elsewhere. The Japanese health ministry says it’s important to strike a balance between continuity of universal health insurance system and innovation as they pursue to reform. The new system should benefit to people in terms of cost and quality. These new plans go against the ideas of 2010, when Japan promised to keep prices of new drugs at levels as set by the government. Recently, Japan stated that it would revise these plans from 2010 and will introduce a new pricing system that evaluates innovation and the cost effectiveness of drugs.
EMA / FDA
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- Fluciclovine (Axumin, Blue Earth Diagnostics) as a diagnostic agent for the detection of recurrence of prostate cancer with PET imaging. Fluciclovine tagged PET scans have shown to be more sensitive compared to CT scans or [11C]-tagged choline PET scans.
- Dinutuximab beta (Dinutuximab beta Apeiron, Apeiron Biologics) for the treatment of high-risk neuroblastoma in children and adults. The monoclonal chimeric antibody targeting ganglioside GD2 was designated as an orphan medicinal product in November 2012. It was also concluded that the active substance in dinutuximab beta could not be considered a new active substance.
The CHMP adopted a positive opinion for the extension of:
- Pembrolizumab (Keytruda, Merck Sharp & Dohme) as monotherapy for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed an autologous stem cell transplantion (ASCT) and brentuximab vedotin (BV), or who are transplant-ineligible and have failed BV. Pembrolizumab is already approved for advanced melanoma and several forms of Non-Small Cell Lung Cancer (NSCLC).
- Nivolumab (Opdivo, Bristol-Meyers Squibb Pharma) as monotherapy for the treatment of Head and Neck Squamous Cell Cancer (HNSCC) in adults progressing on or after platinum-based therapy. The anti-PD-1 monoclonal antibody is already approved for melanoma, NSCLC, Renal Cell Carcinoma (RCC) and classical Hodgkin Lymphoma (cHL).
The FDA granted regular approval for:
- Palbociclib (Ibrance, Pfizer) for the treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women. The selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6 already received accelerated approval in combination with letrozole in 2015, and in combination with fulvestrant in 2016.
- Osimertinib (Tagrisso, AstraZeneca Pharmaceuticals) for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy. In November 2015, the tyrosine kinase inhibitor received accelerated approval for this indication based on an overall response rate (ORR) of 59% among 411 patients in two single-arm clinical trials.
- Niraparib (Zeluja, Tesaro) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. The PARP-inhibitor was granted fast track designation.
The FDA granted accelerated approval for:
- Avelumab (Bavencio, EMD Serono) for the treatment of patients 12 years and older with metastatic Merkel Cell Carcinoma (MCC). The PD-L1 inhibiting monoclonal antibody is the first FDA-approved product to treat this type of cancer.
- Ribociclib (Kisqali, Novartis Pharmaceuticals) in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. The cyclin-dependent kinase 4/6 inhibitor is now recommended as first-line treatment and is currently in clinical trials for several other indications, including neuroblastoma and malignant rhabdoid tumors.
- Pembrolizumab (Keytruda, Merck and Co.) for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or those who have relapsed after three or more prior lines of therapy. The PD-1 inhibitor was earlier approved for Melanoma, Non-Small Cell Lung Cancer (NSCLC) and Head and Neck cancer.