How do medicines make it to market and what is NICE’s role in the process?
Technology appraisals: Where potential can flourish
Technology appraisals are recommendations by NICE on the use of new and existing medicines and treatments within the NHS. They are either:
• Single technology appraisal (STA): Used to assess new technologies; a single drug or treatment, usually new pharmaceutical products or license extensions for existing products. NICE also uses STA for reviews of some published appraisals. This process enables NICE to produce guidance soon after the technology is introduced in the UK.
• Multiple technology appraisal (MTA): Used to assess several drugs or treatments for one condition.
• Fast track appraisal (FTA): In April this year, the FTA process was introduced to speed up access to the most cost-effective new treatments.
Appraisals assess medicines, medical devices, diagnostic techniques, surgical procedures and health promotion activities.
NICE bases its recommendations on a review of clinical and economic evidence. Clinical evidence shows how well the medicine or treatment works and economic evidence demonstrates how well the medicine or treatment works in relation to how much it costs the NHS, and whether it represents value for money. Each appraisal can receive one or more recommendation, and can comprise more than one type of recommendation.
NICE has five decision types:
The drug or treatment is recommended for use:
• In line with marketing authorisation from the European Medicines Agency (EMA) or Medicines and Healthcare Products Regulatory Agency (MHRA), or
• In line with how it is used in clinical practice in the NHS (or both).
The technology is recommended for a smaller subset of patients than originally stated by the marketing authorisation.
Only in research
The drug or treatment is recommended for use only in the context of a research study, for example a clinical trial. This sometimes happens for new technologies when there isn’t yet enough clinical evidence to make a recommendation for use in the NHS.
The treatment is not recommended when there is a lack of evidence for the clinical effectiveness of the technology, or if it’s not considered to be a cost-effective use of NHS resources compared with current NHS practice.
Recommended for use in the CDF
If there is early evidence that a drug has clinical benefits for cancer patients, but still needs more evidence to prove its cost effectiveness, then it can be recommended for use within the Cancer Drugs Fund, which means that new cancer drugs can be made available to patients much more quickly than before. Source: nice.org.uk
Making it to market
In Europe the European Medicines Agency (EMA) carries out the role of granting marketing authorisations, which allow the manufacturer to sell and promote the new medicine for the indication(s) that the regulatory agencies have assessed and approved.
Many UK assessments are carried out by the Medicines and Healthcare Products Regulatory Agency (MHRA). Each medicine is assessed to determine if it does what it claims to do. In addition, judgement is made on ‘benefit to harm’ balance.
Adcetris (brentuximab vedotin)
At the end of August 2017, Takeda’s Adcetris was recommended as an option to treat systemic anaplastic large cell lymphoma (sALCL), a very rare and aggressive cancer of the lymphatic system, on the NHS in England and Wales.
In June this year NICE decided not to recommend routine funding for the drug, asking Takeda for a revised cost-effectiveness analysis. The drug has been available on the NHS in England via the CDF since April 2013.
The final appraisal, however, recommended Adcetris as an option for treating relapsed or refractory sALCL, but only if patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and the company provides the drug as per the terms of a commercial access agreement with NHS England.
Although “pleased” with NICE’s decision, Takeda professed to be “disappointed” with the restriction. Adam Zaeske, Takeda UK General Manager, said at the time: “It is disappointing that NICE has added a last minute ECOG restriction that could result in a small number of patients no longer having access to the medicine and being left with limited options.”
NICE recommended Bayer’s sorafenib for use on NHS England for the treatment of patients with advanced hepatocellular carcinoma (HCC) who have a Child-Pugh grade A liver impairment and have failed or are unsuitable for surgical or loco-regional therapies.
Bayer agreed a commercial access agreement with NHS England that provides the drug – the only approved pharmacological option for patients with HCC – at an undisclosed discounted price.
Sorafenib works by stopping the proteins on the surface of cells, inhibiting tumour growth. It is estimated that it extends life by at least three months.
Previously, treatments for patients with advanced liver cancer were limited. Andrew Langford, Chief Executive of the British Liver Trust, said at the time: “Evidence shows that outcomes for people with advanced liver cancer are particularly poor, so any increase in length of life is very important.”
Case study: Volte face
The decision not to recommend a drug or treatment need not spell the end of hope for patients in need of it. In June 2017, NICE performed a U-turn that was welcomed by breast cancer sufferers, patient groups, charities and clinicians, as the regulator reversed its provisional decision not to recommend Roche’s Kadcyla® (trastuzumab emtansine) for incurable HER2-positive advanced breast cancer in England.
The positive decision followed a four-year campaign to secure routine access to Kadcyla, a treatment already available for access in Scotland and 15 other European countries. The decision reversed the previous draft guidance issued in December 2016, which rejected Kadcyla’s use on the NHS in England. Close collaboration between Roche, NHS England and NICE resulted in NICE recommending Kadcyla as a cost effective treatment. The decision is expected to benefit nearly 1000 women across the UK each year.
In the pivotal EMILIA study on 991 women, Kadcyla was shown to increase the median overall survival in women with advanced HER2–positive breast cancer, previously treated with Herceptin and a taxane, by 5.8 months compared with lapatinib and capecitabine.
In response to the positive decision, Dr Andreas Makris, Consultant Clinical Oncologist, Mount Vernon Cancer Centre, Middlesex, commented: “Kadcyla is an important treatment option, able to extend life for an average of six months, giving women the invaluable time to spend with their loved ones that they deserve.”
Richard Erwin, General Manager of Roche, called it, “a positive example of how solutions can be reached when all parties show flexibility”.
Industry insider view: James Read
Director, Policy & Communications External Affairs, MSD UK
MSD has achieved a number of successful recommendations from NICE in recent years, including a series of cancer indications for pembrolizumab. Industry and NICE, however, will need to overcome some important challenges if we are to ensure that UK patients can promptly access new medicines that might be able to help them.
The Government’s recently published Life Sciences Industrial Strategy recognises many of the issues and proposes that new medicines be appraised through a single, value-led process, managed by NICE. It will include opportunities for a range of flexible funding and reimbursement vehicles, alongside the ‘NHS Adoption Plan’ for the individual medicine.
In the coming years, companies will be seeking many more recommendations for innovative medicines. That will include a range of treatments across many different cancers often in combination with other therapies, supported by a wide variety of clinical evidence. We are confident that together we will find ways to make sure patients can access important new treatments, helping the NHS to keep advancing outcomes for people affected by serious illness across the UK.
Winners & Losers
Name: Ibrutinib aloneFor: Previously treated chronic lymphocytic leukaemia and untreated chronic lymphocytic leukaemia with 17p deletion or TP53 mutation.
Name: Pomalidomide, in combination with low‑dose dexamethasone For: Multiple myeloma previously treated with lenalidomide and bortezomib.
Name: EverolimusFor: Advanced renal cell carcinoma after previous treatment.
Name: Pegylated liposomal irinotecan in combination with 5‑fluorouracil and leucovorin For: Pancreatic cancer after gemcitabine.
Name: High-dose imatinib For: Treating imatinib-resistant or intolerant chronic myeloid leukaemia.