- Updated draft hypertension guidance reduces threshold for CVD risk.
- Benralizumab recommended for severe eosinophilic asthma in final guidance.
- Blinatumomab not recommended for acute lymphoblastic leukaemia in draft guidance.
- More people with severe to profound deafness to be eligible for cochlear implants with updated guidance.
- Intrapartum care for women with existing medical conditions or obstetric complications and their babies: guideline published.
- CHMP recommends eight medicines for approval:
- Ondexxya: an antidote for medicines apixaban or rivaroxaban, when reversal of their action is needed due to life-threatening or uncontrolled bleeding.
- Waylivra: for familial chylomicronaemia syndrome.
- Dectova: for complicated and potentially life-threatening influenza (under exceptional circumstances only).
- Lorviqua: for anaplastic lymphoma kinase-positive advanced lung cancer.
- Palynziq: for patients aged 16 and older with phenylketonuria.
- Zynquista: as an adjunct to insulin for certain patients with type 1 diabetes.
- Skyrizi: for the treatment of moderate to severe psoriasis.
- Pazenir: for metastatic breast cancer and lung cancer.
- Applicant for Doxolipad requests re-examination of adopted negative opinion.
- Extensions of indication recommended for five medicines.
- First guidance on new rules for certain medical devices published.
- Drug alert class 4 issued for Paracetamol 10mg/ml Solution for Infusion: Accord.
- Medical device alerts issued:
- All T34 ambulatory syringe pumps.
- All Bard urogynaecological mesh – voluntary product withdrawal, implanted devices do not need to be removed
- Therapy to be given as part of plan to tackle diabulimia.
- PrEP Impact Trial to be expanded.
- Pharmacies now able to dispense controlled drugs via Electronic Prescription Service.
- App launched for mobile devices to help detect hearing loss.
- Report suggests drug-resistant gonorrhoea compromises recommended treatment in Europe.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
UPDATED DRAFT GUIDANCE ON THE DIAGNOSIS AND MANAGEMENT OF HYPERTENSION IN ADULTS REDUCES THRESHOLD FOR CVD RISK
NICE has published a draft updated guideline on the diagnosis and treatment of hypertension. The new draft guideline supports the direction of the NHS Long Term Plan and CVD ambitions to improve outcomes in cardiovascular disease (CVD), including preventing strokes and heart attacks, through better detection and treatment of high blood pressure. One of the most significant changes to the guidance originally published in 2011 is the reduced threshold for CVD risk at which treatment for high blood pressure should be considered. The draft guideline recommends that blood pressure lowering drugs should be offered to people aged under 80 with a diagnosis of stage 1 hypertension who have an estimated 10-year risk of CVD of 10% or more. The draft guideline also considered new studies suggesting people with blood pressure below 140/90mmHg might also benefit from medication and what the effect would be of lowering the blood pressure target for people on treatment. However, some of these studies, which formed a key part of the evidence reviewed in other recent international hypertension guidelines, were difficult to interpret because although they recruited people with raised blood pressure who had increased CVD risk, they also included people who had other CVD risk factors such as established blood pressure-related organ damage from previous CVD, or chronic kidney disease. Therefore, these studies could not be directly used to inform the recommendations in this draft guidance. The draft guideline is open for public consultation until 23 April 2019. Final guidance is expected to be published in August 2019.
BENRALIZUMAB RECOMMENDED FOR SEVERE EOSINOPHILIC ASTHMA IN FINAL GUIDANCE
NICE has published final guidance which recommends benralizumab (Fasenra), as an add-on therapy, as an option for treating severe eosinophilic asthma that is inadequately controlled in adults despite maintenance therapy with high-dose inhaled corticosteroids and long-acting beta-agonists, only if:
- the person has agreed to and followed the optimised standard treatment plan and
- the blood eosinophil count has been recorded as 300 cells per microlitre or more and the person has had four or more exacerbations needing systemic corticosteroids in the previous 12 months, or has had continuous oral corticosteroids of at least the equivalent of prednisolone 5 mg per day over the previous six months (that is, the person is eligible for mepolizumab) or
- the blood eosinophil count has been recorded as 400 cells per microlitre or more with three or more exacerbations needing systemic corticosteroids in the past 12 months (that is, the person is eligible for reslizumab).
Benralizumab is recommended only if the company provides it according to the commercial arrangement. See NICE’s guidance for full recommendations.
BLINATUMOMAB NOT RECOMMENDED FOR ACUTE LYMPHOBLASTIC LEUKAEMIA IN DRAFT GUIDANCE
NICE has published draft guidance which does not recommend blinatumomab (Blincyto) for treating acute lymphoblastic leukaemia in adults with Philadelphia-chromosome-negative CD19-positive B-precursor whose disease is in first or second complete remission with minimal residual disease (MRD) of at least 0.1%. The committee concluded that blinatumomab has significant clinical benefits but that further evidence on cost-effectiveness is required to assess its plausibility for NHS funding. NICE has requested further clarification from the company for the second committee meeting in April. Closing date for comments is 25 March 2019.
MORE PEOPLE WITH SEVERE TO PROFOUND DEAFNESS TO BE ELIGIBLE FOR COCHLEAR IMPLANTS WITH UPDATED GUIDANCE
NICE has published new guidance that updates and replaces technology appraisal guidance TA166 following a review of the criteria for defining severe to profound deafness, which is used to identify if a cochlear implant might be appropriate. Severe to profound deafness is now recognised as only hearing sounds louder than 80dB HL at two or more frequencies without hearing aids. Previously it was defined as only hearing sounds louder than 90dB HL. According to NICE, it is estimated that currently around 1,260 people in England receive cochlear implants each year. These updated recommendations could lead to a 70% increase in that number, to 2,150 people, once a steady state is reached in 2024/25.
INTRAPARTUM CARE FOR WOMEN WITH EXISTING MEDICAL CONDITIONS OR OBSTETRIC COMPLICATIONS AND THEIR BABIES: GUIDELINE PUBLISHED
NICE has published a guideline which covers care during labour and birth for women who need extra support because they have a medical condition or complications in their current or previous pregnancy. The guideline also covers women who have had no antenatal care. It aims to improve experiences and outcomes for women and their babies. This guideline includes recommendations on:
- heart disease, bleeding disorders and subarachnoid haemorrhage
- asthma, long-term systemic steroids and obesity
- acute kidney injury and chronic kidney disease
- sepsis and intrapartum haemorrhage
- previous caesarean section and labour after 42 weeks
- small-for-gestational-age baby and large-for-gestational-age baby
- no antenatal care
NICE has also produced a guideline on care during labour and birth for healthy women and their babies.
EUROPEAN MEDICINES AGENCY
CHMP RECOMMENDS EIGHT MEDICINES FOR APPROVAL AND EXTENDS INDICATIONS FOR FIVE
The European Medicines Agency’s (EMA) human medicines committee (CHMP) has recommended eight medicines for approval, including two orphan medicines in its February 2019 meeting:
- Conditional marketing authorisations were granted for:
- Ondexxya (andexanet alfa), as an antidote for adult patients taking the anticoagulant medicines apixaban or rivaroxaban, when reversal of their action is needed due to life-threatening or uncontrolled bleeding.
- Waylivra (volanesorsen), the first medicine for the treatment of familial chylomicronaemia syndrome. Waylivra was designated as an orphan medicine during its development.
- Dectova (zanamivir), for the treatment of complicated and potentially life-threatening influenza (under exceptional circumstances only).
- Lorviqua (lorlatinib), for the treatment of patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer.
- Positive opinions were adopted for:
- Palynziq (pegvaliase), for patients aged 16 and older with phenylketonuria. Palynziq was designated as an orphan medicine during its development.
- Zynquista (sotagliflozin) as an adjunct to insulin for certain patients with type 1 diabetes.
- Skyrizi (risankizumab) for the treatment of moderate to severe psoriasis.
- In addition, the Committee recommended for approval the generic medicine Pazenir (paclitaxel), for the treatment of metastatic breast cancer and non-small cell lung cancer.
Furthermore, the applicant for Doxolipad (doxorubicin) has requested a re-examination of the Committee's negative opinion adopted at the January 2019 meeting. The CHMP will now re-examine the opinion and issue a final recommendation.
The CHMP also recommended an extension of indication of Dupixent (dupilumab) as an add-on maintenance treatment for patients 12 years and older with certain forms of severe asthma. Other extensions of indication recommended by the Committee include Lynparza (olaparib), Riarify and Trydonis (beclometasone/formoterol/glycopyrronium bromide), and Viread (tenofovir disoproxil).
FIRST GUIDANCE ON NEW RULES FOR CERTAIN MEDICAL DEVICES PUBLISHED
The EMA has published the first of a series of guidance documents to help applicants prepare for obligations stemming from the new EU regulations on medical devices. The new regulations introduce new roles and responsibilities for EMA and national competent authorities (NCAs) in relation to certain types of medical devices and in-vitro diagnostics. This first questions and answers (Q&A) document focuses on the implementation of Article 117 of the medical devices regulation, which stipulates that marketing authorisation applications for medicines with an integral medical device must include the results of the device’s assessment of conformity by a notified body. Approximately one in four centrally authorised medicines includes a medical device component, and the majority of these involve an integral device. This includes pre-filled syringes and pens, patches for transdermal drug delivery and pre-filled inhalers. The EMA will publish further updates to the Q&A document addressing other requirements for various categories of devices, including those made of substances that are systemically absorbed, products which are not clearly defined as medicinal products, known as ‘borderline products’, and in vitro diagnostic tests used to determine patients’ eligibility for a specific medical treatment.
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
DRUG ALERT CLASS 4 ISSUED FOR PARACETAMOL INFUSION, ACCORD
The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a class 4 drug alert for Paracetamol 10mg/ml Solution for Infusion, manufactured by Accord Healthcare Limited, who has informed the MHRA that there is an error on the portion of the Patient Information Leaflet (PIL) which is intended for healthcare professionals. The PIL for Paracetamol 10mg/ml Solution for Infusion is a joint PIL between the 50ml vial and the 100ml vial. The error applies to the 50ml vial, which is not currently marketed. The 100ml vial is restricted for use in adults, adolescents and children weighing more than 33kg but it cannot be ruled out the that it is being used for the treatment of term newborn infants, infants, toddlers and children weighing 33kg or less. In the incorrect version of the PIL, the maximum volume of solution for administration to babies and infants weighing 10kg or less is given as 75ml on the dosage table intended for Healthcare professionals. The correct maximum volume for administration to this group is 7.5ml. The PIL has already been corrected and can be accessed here.
MEDICAL DEVICE ALERT ISSUED FOR ALL T34 AMBULATORY SYRINGE PUMPS
The MHRA has issued a medical device alert stating that all T34 ambulatory syringe pumps need a sponge pad fitted to the battery compartment to prevent battery connection issues. Caesarea Medical Electronics (CME) Ltd, have provided instructions to reduce the risk of delay to therapy and loss of infusion if the battery loses connection. The battery that was originally validated for use in the T34 pump was the Duracell (MN1604) 6LR61 9v battery. There is a +/- 2mm tolerance in size, which is allowed within IEC Standards. However, this could result in the battery moving within its housing, leading to a possible loss of connection. In some circumstances, this may result in the pump shutting down. CME are now rolling out a corrective action to fit sponge pads within the battery compartment of the syringe pumps, in order to improve battery connectivity. CME have undertaken additional battery testing on the Enix NX 6LR61 battery and have confirmed that this brand of battery is still suitable for use in the T34 pump.
ALL BARD UROGYNAECOLOGICAL MESH – VOLUNTARY PRODUCT WITHDRAWAL, IMPLANTED DEVICES DO NOT NEED TO BE REMOVED
The MHRA has issued a medical device alert for all Bard urogynaecological mesh. C.R. Bard (Becton, Dickinson and Company (BD)) has informed the MHRA that surgical mesh used for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) is being withdrawn from hospitals and distribution centres. Bard has taken the decision to stop production of these devices as part of its business strategy. The MHRA understands that Bard are stopping production rather than continuing to invest in clinical data to support additional EU requirements. Therefore, implanted devices don’t need to be removed and no additional follow-up is required for patients implanted with these devices. In addition, healthcare professionals (HCPs) are advised to:
- Identify and quarantine affected, unused devices listed in the manufacturer notice from BARD
- Ensure, in cooperation with implanting surgeons, that suitable alternative devices are available
- Follow the actions listed in the manufacturer notice from BARD
- Report adverse events involving these devices through the local incident reporting system and/or the national incident reporting authority as appropriate: England, Scotland, Northern Ireland, Wales. HCPs are advised to also report directly to manufacturers if the local or national systems do not.
THERAPY TO BE GIVEN AS PART OF PLAN TO TACKLE DIABULIMIA
NHS England has announced patients will receive therapy to counteract the impact of harmful social media, as part of a new NHS service for the rare eating disorder diabulimia. Diabulimia is a condition where people with type 1 diabetes restrict their insulin intake to lose weight and can lead to serious complications. Patients will be coached to deal with unrealistic body images amid increasing concerns about the potential damage social media can have on young peoples’ mental health. Patients who are referred to the new services will also be offered daily structured meal planning and clinical support to manage their insulin intake as well as therapy. The new service will also provide:
- Eating disorder teams including team members specialising in mental healthcare and type 1 diabetes.
- Tailored care ranging from hospital stays where necessary and help in the community to provide advice on diet, insulin doses, as well as mental health support.
- Training for healthcare workers to increase their knowledge of the condition.
- Online learning for people with diabulimia, carers and families.
NHS England will pilot services joining up treatment for diabetes and mental ill health in London and the South Coast and will aim to reduce emergency admissions to hospital for complications resulting from diabulimia.
PREP IMPACT TRIAL TO BE EXPANDED
NHS England has announced new places for the PrEP Impact Trial, which will start to be released following agreement at the PrEP Oversight Board (see OnMedica article). With PrEP significantly exceeding initial expert predictions, trial researchers have argued the trial should be doubled in size to up to 26,000 places so that recruitment could reach a “steady state’ in order to ensure the trial can robustly and scientifically inform the design and rollout of a full national programme in partnership with local authorities. In January, the PrEP Oversight Board confirmed its agreement in principle to double the number of places available on the PrEP Impact trial following expert recommendations by researchers but wanted more information on the impact on services. NHS England has already committed to provide funding for the PrEP drug and research costs for up to 26,000 individuals, based on the current terms. Around 80% of participating clinics have confirmed they have the capacity to accept additional trial places and the majority of sites have also received approval from their Local Authority commissioners to proceed.
PHARMACIES NOW ABLE TO DISPENSE CONTROLLED DRUGS VIA ELECTRONIC PRESCRIPTION SERVICE
Following successful testing, NHS Digital is rolling out Schedule 2 and 3 Controlled Drugs (CDs) via the Electronic Prescription Service (EPS). The functionality has been trialed across 64 GP practices across England, since pilots began in October last year. GP practices will be able to send all Schedule 2 & 3 CDs, except oral liquid methadone, electronically via EPS. Once a GP practice is able to send CDs via EPS, dispensers will no longer receive split prescriptions from them. This update means dispensers will see an increase in these prescriptions electronically over the service, rather than in paper form. Dispensers should be prepared for the change and advise affected patients who already have a nomination, that items can now be automatically sent via EPS to the nominated pharmacy, so patients will not receive any more separate paper prescriptions.
WORLD HEALTH ORGANISATION
APP LAUNCHED FOR MOBILE DEVICES TO HELP DETECT HEARING LOSS
The World Health Organisation (WHO) has launched ‘hearWHO’, a free application for mobile devices which allows people to check their hearing regularly and intervene early in case of hearing loss. The app is targeted at those who are at risk of hearing loss or who already experience some of the symptoms related to hearing loss. The ‘hearWHO’ app is based on a validated digits-in-noise technology: users are asked to concentrate, listen and enter into their mobile devices a series of three numbers when prompted. These numbers have been recorded against varying levels of background sound, simulating listening conditions in everyday life. The app displays the users' score and its meaning and stores the outcome of the test so that the user can monitor hearing status over time. The app can be used by individuals as well as health providers with a view to facilitating hearing screening especially in low-resources settings.
EUROPEAN CENTRE FOR DISEASE PREVENTION AND CONTROL
REPORT SUGGESTS DRUG-RESISTANT GONORRHOEA COMPROMISES RECOMMENDED TREATMENT IN EUROPE
The European Centre for Disease Prevention and Control has published a report which presents the results from the 2016 gonococcal antimicrobial susceptibility sentinel surveillance (Euro-GASP). The report found that in 2017:
- No isolates with resistance to ceftriaxone were detected. The 2017 Euro-GASP results revealed stable cefixime and azithromycin resistance (1.9% and 7.5% respectively) compared with 2016 (2.1% and 7.5%), although the number of countries reporting resistant isolates for both antimicrobials increased.
- 15 countries reported cefixime-resistant isolates, compared with 14 and 9 countries in 2016 and 2015 respectively, and 23 countries reported azithromycin-resistant isolates in 2017, compared with 21 and 18 countries in 2016 and 2015 respectively.
- The proportion of isolates showing ciprofloxacin resistance remained the same as in 2016: 46.5%.
The absence of ceftriaxone resistance and low level of cefixime resistance is encouraging says the ECDC and is most probably partly due to the highly effective dual-therapy regimen (ceftriaxone plus azithromycin) or the ceftriaxone high-dose monotherapy used for the treatment of gonorrhoea in the EU/EEA. However, despite the level of resistance to azithromycin (7.5%) being currently stable, the high level of resistance is concerning. Even though the level of resistance to cefixime is stable, cefixime resistance needs to be monitored closely, particularly as gonococcal strains with resistance to both cefixime and ceftriaxone have been spreading internationally in the last few years. The ECDC concludes that novel antimicrobials and/or new dual antimicrobial therapy regimens and continuing surveillance are essential to ensure that gonorrhoea remains treatable.