Oncology Highlights - June 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
Side effects of CRISPR-Cas9 possibly bigger than expected
One outstanding breakthrough to manipulate the human genome is CRISPR-Cas9. Editing the genome with this technique gives scientists the possibility to alter specific sections of the DNA and therefore the ability to potentially fix genetic illnesses. However, new research has shown that all of this is not that easy. Though only single regions in the genome are supposed to be targeted, often other regions are affected as well. These off-target effects have been known for a while – and where they occur can be predicted using algorithms. However, this new study shows these predictions are underestimating the severity. The study found that there are more than 1000 unexpected mutations, including over 100 large deletions and insertions. Risks from these side effects are thought to be small, though each of them can potentially cause serious side effects. As the study was conducted in mice and was relatively small, it is now investigated how serious these problems are – and how these can be solved. The study was published in Nature Methods.
Personalized pembrolizumab dosing can save nearly $1 billion per year
Immunotherapies are expensive, something that is now heavily debated with regards to all cancer drugs. New calculations shine a bright light on the costs of pembrolizumab, and more specific on how those costs might be unnecessarily high at this point. Pembrolizumab (Keytruda) is a human PD-1-blocking antibody indicated for the treatment of metastatic melanoma, metastatic non-small cell lung cancer (NSCLC), recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), and classical Hodgkin lymphoma (cHL). Oncologists have calculated the extra costs because of flat dosing compared to personalized dosing. Pembrolizumab is approved for a personalized dosing of 2 mg/kg per 3 weeks. For a person of 75 kg this would require 150 mg pembrolizumab. As the drug is dosed per 100 mg, this means the flat dosing gives an excess of 50 mg which equals 25%. Personalized dosing of pembrolizumab may have the potential to save approximately $825 million annually in the United States, likely without affecting outcomes. The results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting last month, and published in The Journal of the National Cancer Institute.
Signs of developing gliomas observed years before diagnosis
Growing brain tumors induce changes in immune activity years before any symptoms arise, researchers from the Ohio State University claim. They found that proteins sent by immune cells to signal other immune cells are weakened in the blood, a phenomenon which already can be seen 5 years before the cancer is even diagnosed. Such information can be used to diagnose brain cancer earlier and could lead to better treatment options and more effective interventions. Though preventive screening of the whole human population is an unattainable option, these results can help other investigations to identify gliomas earlier. Moreover, the current research found cytokines that play an important role in the development of brain cancer, results that should be further investigated and evaluated. The study was published in PLOS one.
Parexel to be acquired by Pamploma Capital Management in $5 billion deal
Parexel has entered a definitive agreement to be acquired by the privately owned hedge fund sponsor Pamplona Capital Management for $88.10 per share in cash in a transaction valued at roughly $4.5-5.0 billion. After the recent merger of inVentiv Health and INC Research – in which INC is paying a similar price to inVentiv, estimated at $4.6 billion – rumors already circulated that Parexel was exploring a sale. Along with other combinations such as Quintiles-IMS and Covance-LabCorp, some argue we now have a fourth category added to the already existing categories of ‘large’, ‘midsize’ and ‘niche/small’ CRO, namely ‘mega’. Interesting times in CRO world; the major activity in the top of the hierarchy may result in an extension of large CROs, creating an even bigger distance between the mega and the midsize & niche players.
F-star and Merck agree on €1 billion deal to develop 5 bi-specific antibodies
F-star and Merck have announced a new partnership for the development of five bi-specific immuno-oncology antibodies. With this new agreement, Merck has the option to acquire each of F-star’s five bi-specific programs, including the preclinical lead asset FS118 designed to block LAG-3 and PD-L1. These two pathways are used by cancer cells to evade the immune system. For the other four novel bi-specific antibodies targeting specific pathways, Merck gains exclusive development and commercial rights to augment the anti-tumor immune response. Merck will pay up to €115 million in upfront, R&D funding and milestone payments in the first two years. Further payments are based on milestones.
EMA / FDA
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- Tivozanib hydrochloride monohydrate (Fotivda, EUSA Pharma) for the treatment of advanced renal cell carcinoma (RCC). The protein kinase inhibitor (PKI) blocks vascular endothelial growth factor receptors (VEGFR) and therefore inhibits angiogenesis leading to inhibition of tumor growth.
- Ribociclib (Kisqali, Novartis) for the treatment of locally advanced or metastatic breast cancer. The PKI selectively inhibits cyclin-dependent kinase (CDK) 4 and 6, which are downstream proteins of multiple signaling pathways leading to cellular proliferation.
The U.S. Food and Drug Administration adopted a positive opinion for:
- A combination of dabrafenib and trametinib (Tafinlar and Mekinist, Novartis) for the treatment of metastatic NSCLC with BRAF V600E mutation as detected by an FDA-approved test. Both drugs are already approved separately for several indications with BRAF V600E or V600K mutations. The FDA also approved the Oncomine Dx Target Test (Thermo Fisher Scientific), a next generation sequencing (NGS) test to detect multiple gene mutations for lung cancer in a single test from a single tissue specimen. This is the first NGS oncology panel test that is approved by the FDA for multiple companion diagnostic indications.
- An injection of the combination of rituximab and hyaluronidase human (Rituxan Hycela, Genentech) for adult patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia (CLL). This subcutaneous route of rituximab shortens administration time from several hours to 5-7 minutes. Moreover, the new combination provides for flat dosing.
- Aminolevulinic acid hydrochloride (Gleolan, NX Development) as an optical imaging agent indicated in patients with gliomas as an adjunct for the visualization of malignant tissue during surgery.
FDA publishes: “Use of electronic records and electronic signatures in clinical investigations under 21 CFR part 11 – questions and answers”
The FDA has provided new instructions to guide to sponsors, clinical investigators, institutional review boards (IRBs), contract research organizations (CROs), and other interested parties. This document is intended for the use of electronic records and electronic signatures in clinical investigations of medical products under 21 CFR part 11, Electronic Records; Electronic Signatures. This document discusses the procedures to help ensure that electronic signatures meet FDA requirements and to affirm that they have the same worth as paper records and handwritten signatures. Moreover, the use of a risk-based approach when deciding to validate electronic systems, implement audit trails for electronic records, and archive records that are pertinent to clinical investigations conducted under parts 312 and 812 are highlighted.