Horizon scanning for managing medicines

1. Horizon scanning for managing medicines Produced to support the Prescribing Outlook series November 2011

2. Outline What is horizon scanning and why is it necessary? How does the process of horizon scanning work? What factors affect the prioritisation of new drugs? How can medicines information support the process? What will be the key pressures on medicines budgets in the near future?

3. What is horizon scanning? Horizon Scanning has been defined as:‘the systematic examination of potential threats, opportunities and likely future developments……. ….may explore novel and unexpected issues, as well as persistent problems or trends.'

4. Why horizon scan for medicines? ‘the purpose of horizon scanning is not to predict the future, but to explore ranges of possible futures in order to challenge and inform strategy’ • Manage budgets • Plan services - new and redesign • Anticipate pressures (financial and service delivery) • Identify areas for disinvestment • Manage entry into hospital/ formulary /practice etc • Identify drugs suitable for homecare

5. A woman with advanced kidney cancer and six months left to live says she is missing out on a potentially life-saving drug…….

6. 2010 Prescribing data (England) • The overall NHS expenditure on medicines in 2010 was £12.9 billion. • Hospital use accounted for 31.7% of the total cost (up from 30.9% in 2009) • Cost of medicines rose by 4.8% overall but by 7.7% in hospitals (compared to 5.6% overall but by 13.2% in hospitals in 2009) Hospital Prescribing 2010: England. NHS Information Centre Oct 2011

7. Drivers of growth in prescribing (1) • New drugs for diseases where previous therapeutic/ management options were limited e.g. rare genetic diseases, HPV vaccine • Ageing population • Expanded indications (increase in eligible population) e.g. chemotherapy drugs moving from last-line use to first-line use • Displacement of old drugs with new drugs at higher cost e.g. “biologicals”, oral anticoagulants • New drug regimens or maintenance treatments added to standard therapy e.g. chemotherapy • ‘Medicalisation’ e.g. social phobia

8. Drivers of growth in prescribing (2) • National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), All Wales Medicines Strategy Group (AWMSG) • Quality and Outcomes Framework in primary care • Cancer drugs fund

9. Benefits of advance information • Enables assessment of safety and efficacy • Enables assessment of value or cost effectiveness (rarely) • Informs and primes NHS organisations to implement management strategies

10. The horizon scanning process Systematic early identification (horizon scanning) Filtration and selection Information retrieval Prioritisation not include include Assessment Dissemination

11. Information sources for the horizon scanning process • Specialist media for press releases highlighting • conference presentations • dates for submission to licensing authorities • plans for development • Specialist databases • Journals – specialist and general • General media • Industry (contacts, websites, annual reports) • UK PharmaScan • Licensing agencies • Clinical specialists • Other horizon scanners

12. Filtration and selection PIII or filed in EU (over 500 listed on NDO) Prioritisation…………big hitters!

13. Group work 1Factors that influence prioritisation List factors that influence the impact a new drug/ licence extension/ new formulation might have on an NHS organisation. Hint: Think about which drugs have had a large impact on your organisation over recent years and why this was so.

14. Impact Factors (1) Financial factors • Cost of drug, administration and testing • PbR • Likely Commissioning for Quality and Innovation (CQUIN) target • Will it change where patients are treated e.g. hospital vs. healthcare at home vs. primary care. • Funding of services?

15. Impact Factors (2) Drug properties/therapeutics • Anticipated licensed indication – is it wide or narrow? • Formulation and administration? • First in class? • Place in therapy? • Significant improvement in disease management? • What could be its USP (unique selling point)? • Other trials ongoing? (Licence extensions are easier to obtain and there may be off label use.)

16. Impact Factors (3) External factors • Size of target population i.e. large population or significant subset of large population? What is large? • Local services e.g. tertiary centre • Local use (in ongoing clinical trials or unlicensed use) • NHS priorities? • Where in NICE agenda? • Which company? • Media/public interest

17. Factors used by UKMi for prioritisation • the drug is expected to provide a significant improvement in disease management • the drug is first in class or has a major new indication • there are limited other drug/non-drug alternatives • the drug cost will be high • the target population is large • there is likely to be a significant effect on service implications e.g. route/ formulation/ method of delivery • the drug or disease area is considered an NHS priority • the drug has significant additional indications in the advanced pipeline stage • the drug is in the EU licensing process • there is likely to be significant media interest.

18. UKMi Horizon scanning products Prescribing outlook www.nelm.nhs.uk Password restricted to NHS

19. UKMi Horizon scanning products New Drugs Online (NDO) • Contains over 1300 monographs • Updated daily • In August 2011 • 363 monographs updated • 135 evidence based evaluations added • 2,168 registered users • Monthly newsletter

20. NDO via Evidence in Health and Social care (NHS Evidence) www.nelm.nhs.uk

21. Other UKMi products (all via NeLM) • London New Drugs Group reviews • UKMi/NPC ‘On the horizon’ • New Medicines Profiles • IFR summaries • NICE bites

22. UK PharmaScan • Common horizon scanning database for medicines • Hosted by NICE • Data input regularly by Pharma • For horizon scanning bodies and organisations with NHS planning remits • Developed in collaboration with national horizon scanning organisations (UKMi, SMC, AWMSG, NHSC, NPC, NICE), ABPI and Department of Health • More info at ukpharmascan.org.uk

23. Key pressures on medicines budgets in 2011-2012 due to new medicines

24. Key new drugs or licence extensions anticipated 2011-2012 • Erlotinib for NSCLC • Bevacizumab for ovarian cancer • Lenalidomide for multiple myeloma • Vemurafenib for malignant melanoma • Almetuzumab/ Laquinimod for multiple sclerosis • Strontium for osteoarthritis • Rivaroxaban/ Apixaban for stroke prevention • Dabigatran/ Rivaroxaban/ Apixaban for VTE treatment and long term prevention • C1 esterase inhibitor for hereditary angioedema • Nalmefene for alcohol dependence • Telaprevir for hepatitis C • Exenatide/ Liraglutide plus basal insulin • Pertuzumab for breast cancer

25. Rivaroxaban/ Apixaban Indication: Stroke preventionin atrial fibrillation Impact? Primary care. • Prevalence of AF is about 1,300 per 100,000 people. More than 20% of strokes are attributed to AF. NICE estimates about 47% currently receive an anticoagulant with an additional 30% eligible, but not receiving therapy. Availability of newer anticoagulants may increase the number of patients treated. • There is no requirement for monitoring of anticoagulation with the newer agents but reversing the anticoagulant effect is difficult. This may have implications for at risk patients. Increased cost of these may be offset by reduced monitoring. There may be an impact on commissioning of anticoagulant services. • Dabigatran was recently launched for this indication.

26. Dabigatran/ rivaroxaban / apixaban Indication: Venous thromboembolism treatmentand long term prevention Impact? Secondary and Primary care. • In England in 2009-10 there were over 37,000 finished consultant episodes with a diagnosis of PE (~71 per 100,000 people). Following an episode of VTE, risk of recurrence within 8 years is about 30%. • In primary care, newer drugs may free district nursing services from administration of low molecular weight heparins and a licence for long-term secondary prevention may increase the number of people on anticoagulants. • There isno requirement for monitoring but reversing the anticoagulant effect is difficult which may have implications for at risk patients. • Increased cost of these may be offset by reduced monitoring. There may be an impact on commissioning of anticoagulant services. • Differences in frequency of dosing may be important for compliance in the long-term use.

27. C1 esterase inhibitor Indication: Hereditary angioedema (HAE) – long term prophylaxis. Impact? Secondary care • HAE is a genetic disorder with an estimated prevalence of 1 in 50,000. • Current options for prophylaxis include oral danazol and tranexamic acid; C1-esterase inhibitor may be an option where these are contra-indicated. • C1-esterase inhibitor is much more expensive and there are significant service delivery implications as it is administered i.v. twice weekly. Self-administration may be possible but requires extensive training.

28. Nalmefene Indication: Alcohol dependence. Impact? Primary care • In England, alcohol dependence affects around 4% of people aged 16-65 years. 290 prescription items per 100,000 people were dispensed for alcohol dependency in England in 2010. • Unlike existing drug therapies, nalmefene is used ‘as-needed’ and does not require complete abstinence.This will make it attractive and as a new treatment nalmefene could be expensive.

29. Telaprevir Indication: Hepatitis C (genotype 1) - treatment naïve and resistant patients Impact? Secondary care • HCV infection is under diagnosed but testing is increasing.In 2009, estimates suggest 250,000 people in England and Wales were infected; 146,000 chronically (262 per 100,000). • Genotype 1 is the most resistant form and infects about 40% of patients, of whom up to 60% do not have a sustained virological response to the current standard (peginterferon plus ribavirin). • This, together with the recently launched boceprevir represent a new treatment strategy especially for patients who have failed on standard therapy where further treatment options are limited. As add-on therapy, they will add considerably to the cost of treatment. Boceprevir costs about £100/day.

30. Exenatide/ Liraglutide plus insulin Indication: Type 2 diabetes mellitus (T2DM) Impact? Primary care • In 2009, the UK prevalence of diabetes mellitus in adults was 4% (about 90% with T2DM). It is thought up to 5% of people in England have diabetes, including those undiagnosed. NHS health checks will increase the number diagnosed. • The combination of a GLP-1 and basal insulin will offer an additional treatment step for patients with inadequate control despite several therapies. • The combination is currently used off-label to a limited extent, but licensing may increase use.

31. Pertuzumab Indication: Metastatic breast cancer – first line in HER2-positive. Impact? Secondary care • The incidence of breast cancer in the UK is about 78 per 100,000 people. Up to 40% of patients develop metastatic disease within 10 years and one third of these are HER2-positive (10 per 100,000). • This is likely to be used as add on to standard therapy.

32. Erlotinib Indication: Advanced NSCLC- first line in EGFR positive. Impact? Secondary care • The UK incidence of advanced NSCLC is 40 per 100,000. Of the 25% of patients well enough to receive first-line therapy, 20-40% may be eligible for second-line therapy. • Erlotinib will offer a less complicated and less toxic alternative to first-line i.v. chemotherapy in selected patients. • Current cost of erlotinib is about £1,630 per month. Cost of testing should be taken into account.

33. Bevacizumab Indication: Advanced ovarian cancer – first line. Impact? Secondary care • UK incidence of ovarian cancer is about 21 per 100,000 people. 40% of affected women are diagnosed with advanced disease. • NICE recommends paclitaxel and cisplatin or carboplatin as first-line therapy after surgery. If licensed, bevacizumab will be the first angiogenesis inhibitor for ovarian cancer and used in combination with carboplatin and paclitaxel. • Current cost of six 15mg/kg doses of bevacizumab given in 3-weekly cycles to a 65kg woman is about £14,000. Maintenance dose is 7.5mg/kg 3-weekly.

34. Lenalidomide Indication: Multiple myeloma (MM) - maintenance. Impact? Secondary care • The UK incidence of MM is 6.6 per 100,000 people. Median survival is 3-5 years, increasing to 7 years with intensive therapy. Remission is followed by multiple relapses, and ultimately treatment resistance. • Lenalidomide offers the possibility of prolonged remission and fewer relapses, compared to current therapy. • Cost per 28-day cycle is between £3,570 and £4,368 (5mg and 25mg doses).

35. Vemurafenib Indication: Malignant melanoma. Impact? Secondary care • Incidence of malignant melanoma in the UK is about 15 per 100,000 people, and is doubling every 10-20 years. About 50% are BRAFV600 positive which is associated with increased tumour aggressiveness. • Dacarbazine is the current first-line choice but oral vemurafenib has already attracted media attention. • A test is needed to identify BRAFV600 positive patients. • Vemurafenib is likely to be expensive but could offset current outpatient i.v. administration costs. In the US, a 6-month course will cost $56,400. Cost of the test should be considered.

36. Alemetuzumab/ Laquinimod Indication: Multiple sclerosis – relapsing remitting (RRMS). Impact? Secondary care • In England and Wales the annual incidence and prevalence of MS is 3.5-6.6 and 100-120 per 100,000, respectively. Around 80% have RRMS at onset. • Alemtuzumab is a new class of drug for MS and as a single annual treatment it may be attractive. • As an oral competitor to fingolimod laquinimod will have to be competitive. • Cost of MabCampath brand of alemtuzumab is about £1,300 for a 5 day course. However, as Lemtrada is a new brand for MS the pricing structure may be different and could be in line with the cost of other MS treatments.

37. Strontium ranelate Indication: Osteoarthritis (OA). Impact? Primary care • By the age of 65, at least 50% of people have some degree of joint OA. About 10% of people over 65 have a major disability due to OA. • Strontium will be an add-on therapy for patients who require disease modifying therapy and will be an additional benefit for those with osteoporosis and OA. • Current cost of Protelos is about £30/month and will be an additional treatment cost.