Oncology Highlights - December 2018
We wish you a wonderful start with lots of joy and happiness in 2019! 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
A look back at 2018 oncology advances
The year 2018 has been an eventful year in the field of oncology. Practice-changing new study results, cell therapies, drug price discussions, record IPOs stamped this year in preparation for a competitive and exciting next year ahead. Among the new drugs and combinations approved by FDA, special attention is brought to the approval of larotrectinib for patients with solid tumors that have NTRK gene fusion, the second ever tumor and tissue type agnostic, genetic alteration specific approval since 2017. Another amazing step to precision oncology advancement. While the scientific community is accumulating data for adoptive immunotherapy with CAR T-cells long-term efficacy assessment, which was approved in 2017, first studies of its combination with checkpoint inhibitors appeared. The first two CAR-T therapies became accessible in Europe, also triggering fierce discussions on oncology drug pricing. In terms of lifestyle, new insights gained in the understanding of the link between obesity, cancer and immunotherapy. Increased weight is identified as a risk factor for certain cancer types (e.g. colorectal, kidney, endometrial) with underlying mechanisms effecting immune system. Gut microbiome and antitumor therapy efficacy was highlighted in several studies marking the importance of normal gut microbiome as a part of successful antitumor treatment strategy. Two outstanding scientists, James P. Allison (USA) and Tasuku Honjo (Japan) whose discoveries formed the basis of modern cancer immunotherapy, became laureates of the 2018 Nobel Prize in the field of physiology and medicine. The prize was awarded for their discovery of cancer therapy by inhibition of negative immune regulation. A vast number of combination therapies with immune-checkpoint inhibitors (ICI) showed extended survival, although these benefits did not translate to all patients. Notable optimism for disruptive RNA therapies was marked by the largest IPO in biotech history by Moderna’s mRNA platform before showing clinical utility. 2018 highlights are not limited to what we described above, there were many more of them! We look forward to new discoveries in the upcoming 2019!
Abberant DNA methylation landscape (Methylascape) is linked to cancer. Untill now, studies tried to identify biological consequences of DNA Methylscape changes for specific cancer types through sequencing circulating tumor DNA in liquid biopsy. Researchers at the University of Queensland developed a test exploiting the physicochemical properties of differential methyl cytosine landscape in tumor DNA. They found that when DNA is placed in aqueous solution, tightly-packed clusters of these methyl groups folded into particular nanostructures which then stuck to solid surfaces like gold, allowing them to be easily detected. Based on this observation, they designed a simple test using gold nanoparticles that instantly change color to determine if the 3D nanostructures of cancer DNA are present. This rather inexpensive, universal and fast method will provide a robust and immediate “yes or no” answer under 10 min which will need to further investigated in the clinic. The study is published in Nature Communications. (Image: Sina et al., 2018 Nature Communications)
Dendritic cells (DC) orchestrate the immune response with their ability to sense, process and present antigen to lymphocytes and hence are prominent players of tumor recognition. Currently there are therapies under clinical development based on modifying these DCs from donors to recruit other immune cells in cancer. However, DCs are rare and hard to produce in large numbers. A recent study published by researchers in Sweden tries to overcome this hurdle by using cellular reprograming. The team identified three key genes: PU.1, IRF8, and BATF3 which can reprogram skin fibroblasts into DCs in mouse cell line model. Induction with these transcription factors resulted in cells that can engulf antigens and interact with T-cells like true DCs. The modified cells might be easier to use as they do not require an inflammatory signal in order to mature and present antigens. The group also had proof-of-concept results in human cells with plans to commercialize the technology as a cell therapy for the treatment of cancer. The study is published in Science Immunology. (Image: Rosa et al., 2018 Science Immunology)
M&A news, oncology deals:
- Argenx $1.6B deal with J&J: Johnson & Johnson's Janssen signed collaboration agreement with a potential worth to $1.6B to develop and market Dutch drug maker Argenx' cusatuzumab. J&J will pay $300M upfront cash for cusatuzumab (ARGX-110) is a CD70 antibody and novel checkpoint inhibitor that is currently in phase I/II trials in patients with acute myeloid leukaemia (AML) and high-risk myelodysplastic syndromes (MDS).
- GSK to acquire Tesaro for $5.1B: Glaxo Smith Kline (GSK) agreed to buy Boston based oncology biotech Tesaro with an investment of $5.1B. Tesaro’s Zejula (niraparib), an oral poly ADP ribose polymerase (PARP) inhibitor, is approved in the US and Europe for ovarian cancer. Zejula has a strong market value and demonstrated notable clinical benefit in patients with and without germline mutations in a BRCA gene (gBRCA).
- Gilead-Agenus pact: Gilead Sciences and Agenus have entered into a partnership for the development and commercialization of AGEN1423 as well as the option to license for AGEN1223 and AGEN2373. The agreement includes $1.7B potential worth with milestones and the upfront payment to Agenus $150M upon closing. AGEN1423 is a bispecific antibody with a tumor microenvironment conditioning effect. Similarly, AGEN1223 is also a bispecific that is designed to deplete Tregs. CD137 agonist, AGEN2373 is a positive regulator of activated T-cells.
The Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorization for:
- Zirabev (bevacizumab, Pfizer) for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer (NSCLC), renal cell cancer and carcinoma of the cervix. This anti-VEGF monoclonal antibody is Pfizer’s second therapeutic oncology biosimilar (next to Avastin) to receive a positive opinion from the EMA in 2018 after Trazimera (trastuzumab).
The CHMP extended the therapeutic indication for:
- Adcetris (brentuximab vedotin, Takeda) in adult patients with previously untreated CD30+ stage IV Hodgkin lymphoma (HL) in combination with doxorubicin, vinblastine and dacarbazine (AVD). CD30 directed ADC was first approved in 2011 and is used to treat classical HL as well as anaplastic large cell lymphoma. The recent results presented in ASH meeting demonstrated Adcetris is effective at extending PFS and OS of patients CD30-expressing peripheral T-cell lymphomas (PTCL).
- Rubraca (rucaparib, Clovis Oncology) as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. The PARPi its clinical benefit is supported by the pivotal ARIEL3 study, which provided benefit in all ovarian cancer patient populations.
- Sprycel (dasatanib, BMS) in pediatric patients newly diagnosed Ph+ acute lymphoblastic leukaemia (ALL) in combination with chemotherapy. The TK inhibitor was first approved by the EC in July 2018 and the expansion is based on data from CA180-372 (NCT01460160), an ongoing phase 2 trial in pediatric patients with newly diagnosed Ph+ ALL.
The FDA granted approval for:
- Elzonris (tagraxofusp-erzs, Stemline Therapeutics) blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients aged 2 years and older. The CD123 directed cytotoxin is the first treatment approved by FDA for this rare blood disorder.
- Asparlas (calaspargase pegol-mknl, Servier) as a component of a multi-agent chemotherapeutic regimen for ALL in pediatric and young adult patients. This selective asparagine enzyme kills leukemic cells due to depletion of L-asparagine and permits for a longer interval between doses compared to other available pegaspargase products.
- Lynparza (olaparib, AstraZeneca) for the first-line maintenance treatment of adult patients with BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. The decision is based on the phase III SOLO-3 trial in which PARP inhibitor reduced the disease progression with 70% compared to a placebo. Lynparza has become the first PARP inhibitor to be approved for first-line maintenance therapy.
- Herzuma (trastuzumab-pkrb, Celltrion) for patients with HER2-overexpressing breast cancer. Herzuma is the second FDA-approved trastuzumab biosimilar, following Mylan and Biocon’s approval for Ogivri in December 2017.
- Tecentriq (atezolizumab, Genentech) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. The PD-L1i also won a priority review from FDA for the first-line treatment extensive-stage small cell lung cancer (SCLC).
The FDA granted accelerated approval for:
- Keytruda (pembroluzimab, Merck) for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). Earlier this month, Roche and Merck announced a collaboration to develop a new companion diagnostic for PD1i therapy specifically to assess mismatch repair deficiency (MMR) in solid tumors.
The FDA announced a new framework:
Framework for FDA’s real world evidence program: The FDA unveiled a new framework discussing how the agency will use real-world evidence (RWE) and real-world data (RWD) to help companies win new indications for approved drugs and biologics, expand labels or satisfy post-approval study requirements. The framework defines RWE and RWD, their use in clinical trials, potential trial designs with RWD/RWE, regulatory considerations and data standards for integration and submission to FDA. Medical devices are not covered in the framework.