Avelumab has been approved for treatment of Merkel cell carcinoma in the US
The US Food and Drug Administration (FDA) has granted accelerated approval to avelumab (Merck KGaA and Pfizer) for treatment of metastatic Merkel cell carcinoma (MCC), which is a rare and aggressive form of skin cancer. Avelumab, a PD-L1-specific MAb, thus becomes the fourth checkpoint inhibitor approved for cancer treatment and first systemic therapy for MCC.
The approval is based on a small single-arm study, in which one third of the 88 tested patients responded to treatment. Avelumab is being tested in >20 studies in a variety of cancer types.
HPV vaccine is safe in pregnancy, study finds
The quadrivalent HPV vaccine (Gardasil, Merck & Co. Inc.) administered to pregnant women is safe, according to a large-scale retrospective study.Citation1 The vaccine did not increase the risk of spontaneous abortion, preterm birth, low birth weight of the infant or any major birth defect. The study investigated data from Danish national registries during 2006-13 and compared 1,665 pregnant women who inadvertently had been given the vaccine to 6,660 unexposed subjects. It should be noted that the quadrivalent vaccine was replaced by the nonavalent vaccine since the time of this study.
“Before our study, very little was known about the safety of HPV vaccination in pregnancy,” co-author Anders Hviid of Statens Serum Institut told Reuters. “The lesson is that for young women who are inadvertently vaccinated early in pregnancy there is no need to worry; our results do not support that this exposure has an adverse effect on the unborn baby.”
- Scheller NM, Pasternak B, Mølgaard-Nielsen D, Svanström H, Hviid A. Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes. N Engl J Med 2017; 376(13):1223-1233
First immunotherapy for house dust mite allergy approved by FDA
The FDA has approved Odactra (Merck & Co. Inc.), a sublingual immunotherapy tablet, for treatment of house dust mite-induced allergic rhinitis in adults aged 18-65. Clinical trials have shown that Odactra is 16-18% effective in reducing symptoms.
House dust mites are one of the most common causes of allergy in the world affecting hundreds of millions of people. The tablet, which contains allergen extracts, is administered for 8-14 weeks in increasing doses for desensitization of the patient's immune system.
Ocrelizumab becomes the first approved treatment for multiple sclerosis
The immunosuppressive MAb ocrelizumab (Ocrevus, Roche) won approval by the FDA for patients with multiple sclerosis (MS). Clinical trials have shown that ocrelizumab prevented disease progression in almost 50% of tested subjects with a progressive form of the disease. The number was 75% for patients with relapsing MS.
MS, which affects ∼400,000 people in the US alone, is a neurological autoimmune disease in which myelin sheaths of the nerve axons are destroyed by the immune system. Ocrelizumab targets the CD20 antigen on the B cells.
Heat-stable rotavirus vaccine efficacious in late-stage trial
The pentavalent rotavirus vaccine candidate BRV-PV (Rotasil, Serum Institute of India) prevented 67% of severe rotavirus gastroenteritis cases in a placebo-controlled, Phase 3 trial involving >3,500 healthy infants in Niger.Citation1 This is a higher efficacy than that of the two approved rotavirus vaccines Rotarix (61%) and RotaTeq (39%).
In addition, unlike the two vaccines in use, BRV-PV is heat-stable (two years at 37°C, six months at 40°C), and the doses were not refrigerated during the trial.
Rotavirus causes one of the most severe childhood illnesses in the developing world. >200,000 children under age 5 years die every year due to the infection linked to severe diarrhea, vomiting and fever.
- Isanaka S, Guindo O, Langendorf C, Matar Seck A, Plikaytis BD, Sayinzoga-Makombe N, McNeal MM, Meyer N, Adehossi E, Djibo A, Jochum B, Grais RF. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger. N Engl J Med 2017; 376(12):1121-1130
Neoantigen cancer immunotherapy enters clinical trials
The first of a pipeline for personalized cancer vaccines will be tested in a Phase 1 trial in a variety of cancers. The live, attenuated double-deleted Listeria platform (Advaxis and Amgen) utilizes the bacterial vector for delivery of neoantigens identified by sequencing of the resected tumor. Researchers hope to elicit both cell and antibody responses against the tumor cells boosted by the presence of the Listeria bacterium.
Preclinical trials showed that the platform elicits strong innate and adaptive responses, and remodels the tumor microenvironment to increase T-cell infiltration. The neoantigen vaccine is also being tested in combination with checkpoint inhibitors.
Europe's committee recommends group B meningococcal vaccine Trumenba
The European Medicines Agency's Committee for Medicinal Products for Human Use has recommended approval of the meningitis B vaccine Trumenba (Pfizer) for people 10 years and older. The verdict is based on clinical data on >20,000 adolescents and adults showing that Trumenba is safe and induces protective antibody responses.
The recombinant vaccine contains two variants of the lipidated factor H binding protein found on the surface of Neisseria meningitis serogroup B. It was approved in the US in 2014.
Early trial will investigate oncolytic immunotherapy of myeloma
A dose-escalation Phase 1b trial enrolls 44 myeloma patients across the UK to test oncolytic immunotherapy pelareorep (Reolysin, Oncolytics) in combination with immunomodulatory drugs pomalidomide and lenalidomide.
Pelareorep is based on human reovirus, which preferentially lyses cancer cells, and is designed to induce both innate and adaptive immune responses to create inflamed tumor microenvironment. It is being tested in a variety of cancers in combination with other treatments.
Antibody therapy provided protection from HIV in preclinical models
The combination of two broadly neutralizing HIV antibodies (bNAbs), 3BNC117 and 10-1074, enabled macaques to control infection by simian HIV for extended periods of time.Citation1 Early post-infection treatment was associated with low viremia and persistent T-cell immunity. Six of the 13 tested monkeys controlled the virus up to 13 months after bNAb administration. Overall, 10 monkeys benefited from the treatment.
These bNAbs were isolated from humans with natural resistance to HIV infection. Their therapeutic potential has been explored in clinical trials, and now a trial is underway which also tests the combination.
- Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, Klein F, Gazumyan A, Golijanin J, Donaldson M, Donau OK, Plishka RJ, Buckler-White A, Seaman MS, Lifson JD, Koup RA, Fauci AS, Nussenzweig MC, Martin MA. Early antibody therapy can induce long-lasting immunity to SHIV. Nature 2017; 543(7646):559-563