Oncology Highlights - December 2017
We wish you a wonderful start with lots of joy and happiness in 2018! Thanks to all our subscribers and partners for following Oncology Highlights throughout the year. We look forward to bringing you the most interesting insights in the New Year!
The SMS-oncology team
Oncology Highlights year in review 2017
What really mattered in 2017? We prepared the most read highlights of science events and news that shaped the year. Take a look back in our oncology highlights review!
Cell therapies: This year saw the first (and the second) approval of a sophisticated cancer treatment: CAR-T cell therapy. Novartis its drug Kymriah was approved for the treatment of B-cell acute lymphoblastic leukemia (ALL) in August and its first competitor Gilead’s Yescarta for the treatment of B-cell non-Hodgkin lymphoma in October.
Genetics bonanza: While the CRISPR/Cas9 patent fight goes on, gene editing for clinical use in assisted reproduction leapt forward in 2017. With six studies the total number of papers on the topic quadrupled. In August, a team announced the first use of the CRISPR/Cas9 gene-editing system to repair a disease-causing mutation in viable human embryos.
EMA is moving to the city of canals: European Union member nations voted to move the European Medicines Agency (EMA) to Amsterdam from its current London headquarters. The EMA employs about 900 people and attracts 36,000 visitors a year to London from government, science and industry. Amsterdam was able to attract the EMA with the promise of “a new office in the Zuidas area of the city, already home to companies including paint maker Akzo Nobel and bank ABN Amro Group.”
Acute lymphoblastic leukemia in 2017: Three groundbreaking immunotherapies for relapsed and/or refractory B-cell ALL were approved based on impressive outcomes observed in clinical trials. INO-VATE (inotuzumab ozogamicin; anti-CD-22 ADC), TOWER (Blinatumomab, anti-CD19/CD3 bi-specific T-cell-engager) and ELIANA (Tisagenlecleucel, anti-CD19 chimeric antigen receptor T cells) trials successfully demonstrated the expected outcomes for approval. Additional breakthroughs included seminal research into ALL genomics and the importance of adherence to chemotherapy, which will have direct implications for clinical care.
Immunotherapy resistance and emerging solutions: Immune checkpoint inhibitors stole the show in oncology drug development for the past years. However, PD-1 and PD-L1 inhibitors have demonstrated limited efficacy for patients raining the hopes out. The biggest challenge now is to understand why results wildly vary between the patients and how to increase clinical benefit. Approaches focusing on solving the puzzle were in highlight of 2017: precision medicine, predictor biomarkers, combination therapy and fundamental research on checkpoint inhibitors.
The FDA pushes for generic drugs: After the appointment of new commissioner at the Food and Drug Administration (FDA), a variety of changes and updates have taken place in the agency. One of the most critical changes has been the move to push competition in the market through the development of generic drugs. After the announcement of drug competition action plan, the FDA published the list of drugs in need of generic candidates on its website, providing companies a guideline on which current drugs had the option to be adapted to a cheaper model. This could open the doors for drug makers to seek untapped areas of care and provide cheaper options for patients.
To design efficient and accurate drug delivery systems remains one of the biggest challenges in oncology drug development. Most of the treatments, although mechanistically successful, fail to make it to the market due to the toxicity from unspecific uptake by other organs, limited tissue penetration and the decrease of effective concentration. A creative approach has been published recently with the use of engineered sperm to target female reproductive track cancer. Scientists in Leibniz Institute managed to hijack the sperm to deliver chemotherapy to cervical cancer cells in a highly targeted manner. “Sperm-Hybrid Micromotor” is fitted with tiny four-armed magnetic harnesses that allowed them to be guided by magnets. When the sperm hit a solid tumor, the arms sprung open, releasing the sperm and allowing them to swim into the tumor. The team loaded sperm-motors with doxorubicin, and released them in a dish containing mini cervical cancer, the sperm swam towards the tumors, killing 87 per cent of their cells within three days. Overall, the technology is promising as sperms are excellent candidates to operate in physiological environments, as they lack pathogeny and proliferative ability to form undesirable colonies, unlike other delivery systems such as viruses. The results were published in ACS Nano.
Heterogeneity of human cancers resulting in the inefficient response and eventually resistance to the therapeutic agents is a substantial obstacle in healthcare. One of the attractive trends in cancer treatment is the use of “combination therapy” of which the popularity is risen after the observed positive outcomes in combination clinical trials such as DNA repair pathway inhibitors and chemo-immuno therapies. Many targeted therapies are currently combined based on molecular reasoning about the functions of targets or evidence of additive or synergistic effects in cell line and animal models. In a recent study published in Cell, scientist aim to dissect the synergistic effect of combined drugs from independent action of each drug in a heterogonous cell population. Looking at the correlation in drug response in patient-derived tumor xenografts and with analysis of previous clinical trial data, Palmer and Solger show that clinical efficacy of many combinations is accurately predicted without drug synergy. Their theory predicts that the superiority of many approved combinations can be explained by the simpler and older ‘‘null-hypothesis’’ of independent drug action. Independent action appears to be a sufficient explanation even for drug trials stratified using response biomarkers (e.g., HER2AMP for trastuzumab). The study aims to shed light on drug independence to optimize designing cancer treatments.
Regeneron and ISA announced a collaboration to jointly fund and conduct clinical trials of the combination treatment in cervical cancer and head-and-neck cancer. The partnership stems from the molecular evidence of correlation between the increased HPV oncoprotein expression with cervical and head-and-neck cancers. Research suggests that approximately 55 percent of cervical cancers and more than 60 percent of head-and-neck cancers are HPV16 positive. Clinical collaboration will involve the treatment with ISA101, an immunotherapy targeting human papillomavirus type 16 (HPV16)-induced cancer, in combination with cemiplimab (REGN2810), a PD-1 (programmed cell death protein 1) antibody. Regeneron and ISA will exchange product supply. In addition, Regeneron will provide an upfront payment and an equity investment in exchange for an option to an exclusive, global license for ISA101.
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- Trastuzumab (Herzuma, Celltrion Healthcare) for the treatment of breast (HER2 positive) and gastric cancer. The biosimilar showed comparable safety, quality and efficacy to its reference drug Herceptin which has been authorized in EU since 2000.
The Food and Drug Administration adopted a positive opinion for:
- Bosutinib (Bosulif, Pfizer) for treatment of patients with newly-diagnosed chronic phase (CP) Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML). The tyrosine kinase inhibitor was granted priority review and orphan drug designation for this application in indicated patients.
- Cabozantinib (Cabometyx, Exelixis) for treatment of patients with advanced renal cell carcinoma (RCC). The Met-c and VEGFR2 tyrosine kinase inhibitor was approved for treatment of patients with advanced RCC who have received prior anti-angiogenic therapy in 2016. Recent approval provides for treatment in the first-line setting.
- Ogivri (Trastuzumab-dkst, Mylan) for the treatment of patients with HER2-overexpressing breast or metastatic stomach cancer (gastric or gastroesophageal junction adenocarcinoma). It is the first biosimilar that has been approved to its reference Herceptin (Trastuzumab, Genentech).