Cristiana Bernini

The European Commission granted a marketing authorization valid throughout the European Union for blinatumomab on 23 November 2015. Blinatumomab is a cancer medicine used to treat adult patients with B-precursor acute lymphoblastic leukaemia (ALL), a type of blood cancer. In B-precursor ALL, certain cells that give rise to B-cells multiply too quickly and eventually these abnormal cells replace normal blood cells. Blinatumomab is used when the ALL has come back or has not responded to previous treatment. It is used when the patients are “Philadelphia-chromosome-negative” (Ph-). This means that some of their genes are not re‑arranged forming a special chromosome called the Philadelphia chromosome, which is found in some patients with ALL. Blinatumomab was designated an ‘orphan medicine’ on 24 July 2009. Blinatumomab is a type of antibody that has been designed to recognise and attach to two proteins:

• CD19, which is found on the surface of all B-cells, including ALL cells;
• CD3 on the surface of T-cells (cells of the immune system responsible for killing pathogens and cancer cells).

Blinatumomab acts as a “bridge” to bring the T-cells and the B-cells together. This activates T-cells, which release substances that eventually kill B-cells.

Blinatumomab has been studied in one main study in 189 patients with Ph- B-cell precursor ALL whose leukaemia had come back or had not responded to treatment. Patients were given Blinatumomab for up to five treatment cycles. In this study, Blinatumomab was not compared with any other treatment. The main measure of effectiveness was based on the percentage of patients who, after two treatment cycles, responded to treatment, measured as resolution of signs of leukaemia and complete or partial normalisation of blood cell counts. The study showed that 42.9% (81 out of 189) of patients given Blinatumomab responded to treatment. In most patients who had a response, there was no evidence of cancer cells left. The average survival time before the cancer came back was around 6 months, which could enable suitable patients to undergo a blood stem cell transplant. The most common side effects with Blinatumomab are infusion-related reactions, infections, pyrexia, headache, febrile neutropenia, peripheral edema, nausea, hypokalaemia, constipation, anaemia, cough, diarrhoea, tremor, neutropenia, abdominal pain, insomnia, fatigue and chills. The most serious side effects were infections, neurologic events, neutropenia with or without fever, cytokine release syndrome, and tumour lysis syndrome. Since Blinatumomab has been granted a conditional approval, the company that markets Blinatumomab will provide data from a larger study comparing the effectiveness Blinatumomab to standard chemotherapy in Ph- B-precursor ALL patients. An additional study will look at the safety and use of Blinatumomab in clinical practise.

The European Commission granted a marketing authorization valid throughout the European Union for Nucala on 2 December 2015. Nucala is an asthma medicine used to treat adults with a particular type of asthma called eosinophilic asthma. It is used with other medicines in patients whose asthma is severe and not well controlled with previous treatments. In eosinophilic asthma, symptoms are associated with having too many of a type of white blood cell called eosinophils in the blood and in phlegm in the lungs. The active substance in Nucala, mepolizumab, is a type of protein called a monoclonal antibody, which attaches to a specific substance in the body. Mepolizumab attaches to a substance called interleukin-5 which encourages the production and survival of eosinophils. By attaching to interleukin-5, mepolizumab blocks its action and thereby reduces the numbers of eosinophils. This helps to reduce inflammation, resulting in a reduction in asthma attacks and improvement of symptoms. The benefits of Nucala in severe eosinophilic asthma that is not well controlled by previous treatment have been shown in three main studies, in which it was compared with a placebo (dummy) injection. The first study involved 616 adults and adolescents given Nucala every 4 weeks for a year, in addition to their regular asthma medicines. The second study involved 576 adults and adolescents given Nucala every 4 weeks for 28 weeks. The main measure of effectiveness in these studies was the number of severe attacks (exacerbations) of asthma that occurred during treatment, which was reduced by about half in patients given Nucala. The third study involved 135 patients with eosinophilic asthma severe enough to need regular treatment by mouth with corticosteroids (potent anti-inflammatory medicines such as prednisone and prednisolone), and the main measure of effectiveness was how much the corticosteroid dose could be reduced using Nucala for 24 weeks compared with placebo. Over half (37 of 69) of the patients given Nucala were able to reduce their daily corticosteroid dose by more than 50% to a dose of 5 mg or less, and 10 of them were able to stop corticosteroids altogether, compared with about a third of those given placebo (22 of 66, of whom 5 were able to stop corticosteroids). The most common side effect with Nucala is headache; reactions at the site of injection and back pain are also common, affecting up to 1 patient in 10.

The United States Food and Drug Administration (FDA) accepted a new drug application for a drug-device for measuring adherence to antipsychotic treatment for adults with schizophrenia, bipolar disorder, or major depressive disorder. The Digital Medicine, first in the world, is a drug/device product that combines Otsuka’s ABILIFY^® (aripiprazole) for serious mental illness, embedded with the Proteus® ingestible sensor in a single tablet to digitally record ingestion and, with patient consent, share information with their healthcare professionals and caregivers. With the consumer’s consent, the sensor communicates with a wearable sensor patch and a medical software application to share information with the consumer’s care team about when the medication was taken. The system also tracks the consumer’s physiological responses, such as sleep patterns and physical activity levels. An estimated average of 50% of patients with chronic diseases in developed countries do not take medicines as prescribed, possibly limiting the effectiveness of those medicines. In the U.S., this may result in an estimated $100-300 billion in avoidable healthcare costs due to direct costs such as unnecessary escalation of treatment as well as indirect costs*1,*2. For example, patients suffering from chronic mental disorders such as schizophrenia are often required to take medication for long periods, and it is not unusual for these patients to discontinue taking their medication, or not take their medication as prescribed, which can lead to disease relapse and recurrence.