Oncology Highlights - September 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
NO blockers might improve efficacy chemotherapy in AML
Chemotherapeutic delivery to Acute Myeloid Leukemic (AML) cells could be improved using cardiovascular drugs, a new study suggests. Researchers from the Francis Crick Institute found that AML triggers blood vessel leakage inside the bone marrow, resulting in a less effective delivery of chemotherapeutic drugs to leukemic cells. While investigating AML xenografted mice, the research group found that the bone marrow of these mice is hypoxic compared to healthy mice. Hypoxia subsequently leads to an increased production of nitric oxide (NO), a chemical compound which is involved in blood vessel relaxation to increase the flow of oxygen-rich blood. The researchers speculated that this NO-induced blood vessel relaxation in the bone marrow of AML mice enables blood to leak through the vessel walls, allowing leukemic cells to evade chemotherapy. Further research supported their hypothesis: treating the AML mice with NO blockers prevented blood vessel leakage, restored normal blood flow, and most importantly allowed chemotherapy drugs to reach the leukemic cells. Further research must prove if NO blockers can improve treatment outcomes in patients as well. The study was published in Cancer Cell.
FDA shuts down two Phase I CAR-T trials
US based biopharmaceutical company Cellectis was forced to shut down their two running Phase I trials testing “off the shelf” CAR-T therapy. The two trials tested the prospective cancer therapy UCART123, an allogenic therapy – meaning that T cells from any donor can be used. This way, Cellectis aimed to develop a cheaper alternative for the autologous therapies most companies develop. For example, Novartis its CTL019 is heavily debated as a one-time treatment with their autologous therapy costs $475.000. Both Cellectis trials were stopped after a 78-year-old male with blastic plasmacytoid dendritic cell neoplasm died after experiencing cytokine release syndrome (CRS). CRS is a common immune system reaction to immune therapies, including CAR-T treatments. However, in this specific case the CRS worsened and eventually was fatal. Another patient, a 58-year-old woman with AML developed CRS as well. After these events, the monitoring committee advised Cellectis to lower the dose of UCART123 in the end August. Early September, the FDA fully suspended both the trials.
Zika virus potential weapon to target glioblastoma
The Zika virus has recently gained publicity as a mosquito carried vector infection. Infections in pregnant women can spread to the fetus, inducing microcephaly. The virus targets and destroys neural progenitor cells, which are the stem cells to differentiate into neurons and glial cells in the central nervous system. A new study investigated the potential of the Zika virus to target glioblastoma stem cells. Glioblastoma stem cells are particularly resistant to known therapies, resulting in poor survival rates and often relapse. In their study, the research group exposed in vitro glioblastoma cells to the virus. The virus targeted and killed glioblastoma stem cells specifically, rather than other (healthy) brain cells or other types of glioblastoma cells. Doing the same experiments in vivo in mice, a decrease in tumour growth was observed. Combining the viral therapy with the chemotherapeutic compound temozolomide, effectiveness was enhanced even more. Further investigation is needed to better and fully understand how the virus works, before potentially clinical use. The preliminary results were published in The Journal of Experimental Medicine.
Merck Sharp & Dohme acquires Rigontec
New Jersey’s Merck acquired German cancer immunotherapy company Rigontec in a deal valued at up to €454 million. This consists of an upfront payment of €115 million, and an additional €349 million in clinical, development, regulatory and commercial milestone payments. In 2014, Rigontec was established as a spin-out of the University of Bonn, Germany. Its lead candidate is in early-stage clinical development as a potential treatment in patients with various tumors, using a novel and distinct approach in cancer immunotherapy to induce both immediate and long-term anti-tumor immunity.
Ergomed acquires PSR Group
London based Ergomed acquired PSR Group, a Dutch CRO specialized in the development of orphan drugs, including many rare cancers. Ergomed agreed to acquire 100 % of PSR Group’s issued share capital with a value up to €5.7 million. The initial consideration will be €3.2 million; the aggregate €2.5 million will be based on the achievement of EBITDA targets for 2017, 2018 and 2019. Ergomed will continue with PSR its global orphan drug development business. This will remain under the PSR brand, meaning it will remain focussed on supporting biotech and pharma companies with their regulatory and clinical development of orphan drugs and providing orphan drug specialized staff.
The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for:
- Padeliporfin (Tookad, Steba Biotech) for the treatment of adult patients with adenocarcinoma of the prostate. The vascular targeted photochemotherapy is also in clinical trials for renal cancer, cholangiocarcinoma, non-small cell lung cancer (NSCLC) and choroidal neovascularization.
- Niraparib (Zejula, Tesaro UK) for the maintenance treatment of ovarian cancer. The PARP inhibitor was designated as an ophan medicinal product in 2010.
- Imatinib (Imatinib Teva B.V., Teva B.V.) for the treatment of leukaemia and gastrointestinal stromal tumours (GIST). This protein kinase inhibitor that inhibits the activity of the Bcr-Abl tyrosine kinase (TK) and several receptor TKs is a generic of Glivec.
- Trastuzumab (Ontruzant, Samsung Bioepis UK) for the treatment of early and metastatic breast cancer, and metastatic gastric cancer. The monoclonal antibody is a biosimilar of Herceptin, and was shown to have the same quality safety and efficacy as the original drug.
- Nilotinib (Tasigna, Novartis) for the treatment of paediatric patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukaemia (CML) in the chronic phase, and paediatric patients with chronic phase Philadelphia chromosome positive CML with resistance or intolerance to prior therapy including imatinib. Until now, the tyrosine kinase inhibitor only was approved for adults with the same indication.
The Food and Drug Administration adopted a positive opinion for:
- Gemtuzumab ozogamicin (Mylotarg, Pfizer) for the treatment of newly-diagnosed CD33-positive AML in adults and for treatment of relapsed or refractory CD33-positive AML in adults and in pediatric patients 2 years and older. The anti-CD33 monoclonal antibody can be used in combination with daunorubicin and cytarabine for adults with newly-diagnosed AML, or as a stand-alone treatment for certain adult and pediatric patients. In 2010, Pfizer voluntarily withdrew the drug when a confirmatory Phase III trial did not show a clinical benefit and the rate of fatalities as a result of treatment-related toxicity was significantly higher in the Mylotarg arm.
- Bevacizumab (Mvasi, Amgen) as a biosimilar of Avastin for the treatment of non-squamous NSCLC, glioblastoma, metastatic renal cell carcinoma (RCC), cervical cancer and several forms of metastatic colorectal cancer (CRC). This humanized monoclonal antibody is the first cancer biosimilar approved by the FDA.
- Copanlisib (Aliqopa, Bayer Healthcare Pharmaceuticals) for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.
- Pembrolizumab (Keytruda, Merck) for the treatment of recurrent locally advanced or metastatic, gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 as determined by an FDA-approved test. Patients must have had disease progression on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy.
- A lower dose of cabazitaxel (20 mg/m2 every 3 weeks) (Jevtana, Sanofi-Aventis) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. Cabazitaxel (25 mg/m2 every 3 weeks) was approved for the same indication in 2010.
- Nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib.