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Cost-effectiveness, current barriers and access to Hepatitis C treatment in Asia

MBBS. PhD, MMed, FAMS(Gastro) Associate Professor Chair, University Medicine Cluster Head, Dept of Medicine, YLL School of Medicine. Adjunct.,Cancer Science Institute National University of Singapore Head /Senior Consultant. Div of Gastro & Hepatology, National University Health System

Dan Yock Young

Disclosure

Consultation/ Advisory Board/ Research Funding

• Gilead

• MSD

• Abbvie

• Sanofi-Aventis

• Novartis

Disease burden of Hepatitis C

EASL guidelines 2015

Regimen HCV Genotype

1a 1b 4 5 or 6

SOF + PR 12 wks 12 wks 12 wks

SMV + PR 12 wks (naive or relapse) 24 wks (partial/null)

12 wks (naive or relapse) 24 wks (partial/null)

Not recommended

LDV/SOF 8-12 wks,† no RBV 12 wks, no RBV 12 wks, no RBV

OBV/PTV/RTV + DSV

12 wks + RBV

12 wks, no RBV

Not recommended Not recommended

OBV/PTV/RTV Not recommended 12 wks + RBV Not recommended

SOF + SMV 12 wks, no RBV 12 wks, no RBV Not recommended

SOF + DCV 12 wks, no RBV 12 wks, no RBV 12 wks, no RBV

Our version of real world…….

• Treatment of Hepatitis C has shifted from a medical limitation to a socio-economic access challenge.

• HCV can be eradicated-screen, treat, track

• Whose duty is it to make treatment accessible?

Who is paying for these drugs?

• Healthpayer

– Single healthpayer- government

– Private Insurance

– Employer

– Co-payment/Government assist

– Self paying

xxx Self-paying

Single health payer

How do payers decide if they should pay for a new treatment

• NICE (UK) NICE accepts as cost-effective if interventions has ICER < than £20,000 per QALY and there should be increasingly strong reasons for accepting as cost-effective interventions if ICER > £30,000 per QALY. NICE guideline manual

• US CEA threshold < USD50000/QALY highly cost-effective < USD100000/QALY – cost-effective >USD100000/QALY

• WHO <1x GDP per capita – highly cost-effective 1-3X GDP per capita – cost-effective >3x GDP – not cost-effective

• Real-life cost-effectiveness ranking It is not about whether a drug is cost-effective or not If there is a fixed budget – which are the treatment which would give me the highest yield for single health dollar- may be better spent on water sanitation, food nutrition etc.

Cost effective vs affordable

BMW

bicycle

motorbike

Chevrolet

$150K $100K $20K $500

Cost/km travelled

US CEA and affordability

• SOF/LDV is cost-effective – ICERs ranged from $9700 to $284 300 per QALY

– Chhatwal et al Ann Int Med 2015

• SOF/LDV cost $12 825 more per QALY than SOC – Najafzade et al Ann Int Med 2015

• Treating all eligible patients in the US compared to SOC would cost an additional USD 65 billion and offset USD 16 billion of costs.

• However, treating half of the

eligible patients in US would cost

$134 billion and is 1/8th of US

health budget 2014 www.usgovernmentspending.com/us

UK EAP

• The NHS (UK) made available 18.7 million pound for treating CHC but this would be sufficient for only 500 people.

Is it affordable in Asia

• Affordability GDP/ capita

Rank Continent GDP per capita (US$)

Year

World Average 18,351 2010

1 Oceania 39,052 2010

2 North America 32,077 2010

3 Europe 25,434 2010

4 South America 9,024 2010

5 Asia 2,941 2010

6 Africa 1,576 2010

7 Antarctica 0 2010

Is it affordable in Asia

• There is still a place for Interferon IL-28B gene favourable for achieving an SVR rs12979860 CC in Caucasian rs8099917 TT in Asians The pooled prevalence of the favourable IL-28B genotype is more common in Asians (73%) than in Caucasians (41%) and African Americans (13%). Among 8 studies on 2,612 Asian HCV patients from Japan, Taiwan and Korea, Asians who have the favourable IL-28B rs8099917 TT gene had an overall Odds Ratio (OR) of SVR 5.66 (95% CI 3.99, 8.02) compared with those without the favourable gene Compared to OR rates 3.88 (95% CI 2.75, 5.49) and 4.63 (95% CI 2.52, 8.50) for Caucasian and Black patients, respectively

• Rangnekar et al. Aliment Pharmacol Ther 2012;36:104-14. • Jimenez-Sousa et al BMC Med 2013;11:6.

• Asian tolerate side effects better ?

Option A- Utopian world

– everyone is entitled to the best treatment.

-- Whoever needs to pay just has to pay.

Option B- Stratify treatment based on need

- Those who need DAA gets DAA

- Those who don’t need DAA gets cheaper but still efficacious Rx and those that fail gets retreated.

Cost-effectivenss of HCV Rx in Singapore. GT1 naïve

BOC (RGT) 29,500 19.56

BOC 36,555 7,055 19.53 -0.03 -235,167 -176,375

IL-28B (PEG/RBV+BOC, RGT) 37,748 8,248 19.13 -0.43 -19,181 -14,386

PEG/RBV 37,916 8,416 18.87 -0.69 -12,197 -9,148

IL-28B (PEG/RBV+BOC) 40,328 10,828 19.16 -0.4 -27,070 -20,303

RVR guided therapy 41,759 12,259 20.13 0.57 21,507 16,130

IL-28B (PEG/RBV+SOF) 52,977 11,218 19.39 -0.74 -15,159 -11,370

Viekira pak 72,416 30,657 20.39 0.26 117,912 88,434

Viekira pak + ribavirin 12 weeks 74,925 2,509 20.39 0 Nil Nil

SOF+ PEG/RBV 87,696 15,280 20.32 -0.07 -218,286 -163,714

SOF + LDV 101,333 28,917 20.42 0.03 963,900 722,925

Viekira pak + ribavirin 24 weeks 148,000 46,667 20.36 -0.06 -777,783 -583,337

SOF + RBV 178,319 76,986 19.83 -0.59 -130,485 -97,864

SOF + SMV 204,019 102,686 20.35 -0.07 -1,466,943 -1,100,207

Compared to no treatment

• When compared to no treatment, all strategies including the all-oral DAA were highy cost-effective with ICER<USD50000.

• Using response guided boceprevir (BOC/RGT, least costly treatment over life-time period) as a base case, peginterferon and ribavirin (PR), 48-week boceprevir, IL-28 guided boceprevir and sofosbuvir were economically dominated by BOC/RGT as they are more costly and less effective.

Oral DAA in Non-cirrhotic HCV

• The all-oral therapies such as Ombitasvir/paritaprevir/ritonavir-dasabuvir and sofosbuvir/ledipasvir had ICER of USD38,780 to USD62,645 relative to BOC/RGT and would be considered to be within cost-effective range given willingness to pay threshold at USD 52,500 (one GDP per capita in Singapore in 2015).

Non-cirrhotic HCV

• But if retreatment is taken into account , i.e. reserving DAA as second line therapy, the oral DAA are not cost-effective as first line therapy

• Oral regimens are only cost-effective compared to Boc/RGT if they are less than SGD47,997 for treatment course

• If cirrhotic , oral DAA are more cost-effective

• the ICER of Viekira Pak and SOF+LDV relative to BOC/RGT was USD 4,505 and USD 10,649 respectively.

Roadmap strategy for naïve non-cirrhotic patients

(ICER, USD 14,336) Is this ethical?

Generic licensing of HCV drugs

• USD 900 for 12 weeks == > extremely cost-effective

• Caveats: -- Pakistan average lifespan 65 years old. No difference in treating HCV. -- The need for universal health coverage for access -- Trained health personnel to reach patients -- Ability to identify patients with disease -anti HCV, HCV RNA, HCV genotyping, fibroscan - convincing patients they need treatment - worry of DAA resistance if not supervised

Is screening cost-effective

• Yes.

• In target population where the prevalence is >1.7%

• Point of care blood test with minimal call back and tracking

• High take up rate for screening

• High adherence rate to treatment

• Successful targeting of 35% of population will reduce end stage disease and HCC by 10%

Conclusion

• HCV treatment is no longer a medical problem but a socioeconomic political issue.

• In countries where patient is direct payer, access to new generation DAA will be limited by cost and healthcare infrastructure.

• Lobbying governments, employer and companies to provide co-payment based on targeted customised treatment algorithm provide a practical strategy to allow access to those who need it rather than those who can afford it.

• HCV in theory, can be eradicated. We need to make it happen.