Savings to the NHS predicted from switching to generic antiretrovirals

1 December 2014. Related: Conference reports, Antiretrovirals, Treatment access, HIV 12 Glasgow 2014.

Polly Clayden, HIV i-Base

If everyone on HIV treatment in the UK switched from patented originator antiretrovirals to generics, there is the potential to save 1.25 billion in NHS drug costs over the next five years (2015-2019), according to modelling data presented at the 2014 HIV Drug Therapy Glasgow Congress.

The switch to generic antiretrovirals would involve HIV positive people increasing their pill count from and average of 2.3 to 3.5 pills a day.

Andrew Hill presented these findings on behalf of colleagues from St Stephens AIDS Trust, Chelsea and Westminster Hospital, and the Research Department of Infection and Population Health, University College, London.

Dr Hill explained that every year the number of people on antiretroviral treatment (ART) in the UK increases by 7-10%. The total number on ART could rise to over 100,000 by 2019, particularly with successful strategies to find the 20-25% of people with HIV who are currently undiagnosed.

Current antiretroviral drug costs to the UK compared to those for low-income countries are shown in Table 1. Prices can be discounted below these listed UK prices – typically by 30%.

* Per person per year £ sterling

Sources: BNF 2014, CHAI 2013, MSF 2014.

Basic patents on individual drugs last for 20 years. After patents expire, drugs can be sold by generic companies at prices that can be 80-90% lower than the discounted originator prices. Table 2 shows how much generic drugs could cost in the UK.

* Per person per year £ sterling

Sources: BNF 2014, CHAI 2013, MSF 2014

There are also evergreen patents – by which originator manufacturers retain royalties on products with patents that would otherwise expire – on co-formulations of drugs. These evergreen patents can last over 10 years after the patents on the individual drugs expire.

Patents on AZT, 3TC, nevirapine, efavirenz and ritonavir have either already expired or are due to expire this year. Abacavir and lopinavir/ ritonavir are due to expire in 2016, tenofovir, atazanavir and darunavir in 2017 and raltegravir in 2025. Co-formulated abacavir/3TC expires in 2019 and tenofovir/FTC in 2024. Patents for fixed dose combinations (FDCs) tenofovir/3TC/efavirenz and tenofovir/3TC/rilpivirine do not expire until 2026. The abacavir/3TC/dolutegravir patent expires in 2029.

At current prices FDCs in the UK cost upwards of £4500 per patient year: tenofovir/3TC/efavirenz £4500, tenofovir/3TC/rilpivirine £5200, and tenofovir/FTC/cobicistat/elvitegravir £7400. The price of abacavir/3TC/dolutegravir in the UK has yet to be announced. Dr Hill noted that using generic abacavir or tenofovir plus generic 3TC plus generic efavirenz or boosted protease inhibitor as single agents (three pills) the price of an ART regimen could be approximately £1000 per patient year in the UK.

For the generics model, the investigators assumed 72,000 people on ART in 2014 rising by 8% per year, with originator companies selling drugs to the NHS at 28% discount on list price. The other assumptions were that generic drugs are 80% cheaper than NHS prices and immediately after patent expiry people switch from originator to generic antiretrovirals.

UK treatment use was estimated using UKCHIC data from 2013; proportions of people using individual antiretrovirals are shown in Table 3.

Two scenarios were used for the generic model:

Option 1 – Use only patented, co-formulated drugs (no generics, originator prices remain stable, dolutegravir introduced at a similar price to originator efavirenz).

Option 2 – 100% switch to generic drugs in the year of patent expiry (2014: 3TC, EFV, ABC, NVP, AZT; 2016: ABC, LPV/r; and 2017/8: TDF, DRV/r, ATV/r).

With Option 1 the average pill count remains at 2.3 per day, with Option 2 this would increase by 1.2 pills to 3.5 per day.

With efavirenz plus two NRTIs as first line ART, switches during 2015-2019 would be: in 2015 from FTC to generic 3TC, switch from Atripla to tenofovir plus generic 3TC plus generic efavirenz; 2016 switch to generic abacavir; 2017-19 switch to generic tenofovir. Generic atazanavir and darunavir would be introduced in 2017-2019. Originator integrase inhibitors and etravirine or rilpivirine would only be used for toxicity switching.

In order to better understand the implications of switching from FDCs to individual tablets, the investigators performed a meta-analysis of nine randomised head-to-head trials, including 2,568 participants. Endpoints included: virological failure, development of resistance, discontinuation due to adverse events, switch due to failure and adherence >95%. There was no significant benefit of FDCs vs individual tablet with regards to virological failure, resistance or discontinuation for adverse events. But, people receiving single tablets were more likely to switch treatment +2.6% (95% CI -0.4 to +5.2%), p=0.05 and there was more likelihood of full adherence with FDCs, +5% (95% CI 1.4 to +8.7%), p=0.007. All differences were within the 10% non-inferiority margin.

The generic model predicated annual NHS costs of antiretrovirals of £2.41 billion with Option 1 vs £1.16 billion with Option 2; a potential saving of £1.25 billion. Annual savings increased stepwise as more generic antiretrovirals became available. The relative costs of Option 1 vs Option 2 were £411 million vs £351 million in 2015, these costs were £559 million vs £168 in 2019.

Comment

This presentation caused quite a stir. Remarks from the audience afterwards included the suggestion that a change from FDCs might not be beneficial for patients and health systems in the long run, that people get attached to one pill once a day, and that changes in products cause confusion. Andrew Hill commented that for most people tolerability is usually more important than one versus two or three pills.

Many researchers and doctors have been very supportive of the potential cost savings to the NHS and have mentioned how much good could be done with this money particularly for HIV prevention and HCV treatment.

It is important that patients, payers, and doctors everywhere understand the difference between the cost and price of drugs. Andrew Hill and his group’s work on pricing of drugs – notably the new HCV direct acting antivirals (DAAs) globally and antiretrovirals in middle income countries – is laudable, and gives enormous credibility to fair pricing and access campaigns.

Reference:

Hill A et al. Predicted savings to the UK National Health Service from switching to generic antiretrovirals, 2014-2018. HIV Drug Therapy Glasgow Congress, 2-6 November 2014. Oral abstract O-216. Journal of the International AIDS Society 2014, 17(Suppl 3):19497.
http://www.jiasociety.org/index.php/jias/article/view/19497
http://aps.mediasite.com/mediasite/Play/82986e5259d94163bd78fb97af5fcdb01d?usehtml5=true