HCV UPDATE Treatment: The Next Wave Access: Myths & Facts NASTAD National Technical Assistance Meeting October 2015 Tracy Swan HCV Treatment • Characteristics of DAA Classes

• Next-generation: FDCs

• Trends: 3somes and Quickies

• HCV Treatment in HIV/HCV DAA CLASSES

NON-NUCLEOSIDE POLYMERASE INHIBITORS (): G1 only, further development/need??

PROTEASE INHIBITORS (/r, Olysio): Usually G1 and G4, tendency for DDIs, possibly more side effects, resistance may not always be persistent—next generation might be pan-genotypic DAA CLASSES NS5A INHIBITORS (, , , ) : pan/multi-genotypic (less information in G4, G5 and G6)—some DDIs, resistance can persist for >2 years stop them from working--next generation more potent, active against resistance?

NUCLEOSIDE/TIDE POLYMERASE INHIBITORS (): pan/multi-genotypic (less information in G4, G5 and G6), few DDIs, resistance does not seem to be a major problem; a few more are finally in development Fixed-Dose Combinations (FDCs)

WHAT’S HERE NOW…. Sofosbuvir + Ledipasvir Paritaprevir/r + Ombitasvir, w/ Dasabuvir

WHAT’S COMING in 2016…. + Sofosbuvir+ Velpatasvir What’s Coming in 2016 once daily DAA fixed-dose combinations, 12 weeks*

Grazoprevir/Elbasvir adults w/ G 1,4 and 6 (TX- naive or -experienced, HIV/HCV; in people w/ cirrhosis or ESRD, and w/OST) ---cure rates generally >90%

Sofosbuvir/Velpatasvir adults with all HCV genotypes (TX-naive or -experienced, people with cirrhosis) ---cure rates generally >90%

*some people may need longer treatment and/or Trend: Couples and 3somes ABT-530 + ABT-493

Sofosbuvir/Velpatasvir + GS-9857

Grazoprevir + MK-3682 + Elbasvir or MK-8408

Odalasvir + AL-335 + Olysio Trend: Quickies • Sofosbuvir/Velpatasvir + GS-9857 for 4 or 6 weeks

• Grazoprevir/Elbasvir + Sofosbuvir for 4, 6 or 8 weeks

• Sofosbuvir + Odalasvir for 6 or 8 weeks G1: Sofosbuvir/Velpatasvir + GS-9857 4 weeks 6 weeks 6 weeks 6 weeks

Gane et al; .EASL 2015 G1: Grazoprevir/Elbasvir + Sofosbuvir

Poordad et al; EASL 2015 G3: Grazoprevir/Elbasvir + SOF 8 weeks 12 weeks 12 weeks

Poordad et al; EASL 2015 G1: Sofosbuvir + Odalasvir: for 6 or 8 weeks

Patel et al; EASL 2015 Treating HCV in HIV/HCV • Cure rates are the same-- sometimes even better

• Drug-drug interactions between ARVs and DAAs can complicate HCV treatment – extra monitoring may be needed; some drugs need to be switched Sofosbuvir/Ledipasvir (Harvoni) in HIV/HCV, G1 or G4, TX-naive or -experienced

ARVs: Atripla or Edurant/ Isentress + Truvada Cooper et al; IAS 2015 ALLY-2: Sofosbuvir/Daclatasvir in TX-naive or -experienced, HIV/HCV G1, 2, 3 ,4

ARVs: all, except Aptivus Wyles et al; CROI 2015 Grazoprevir/Elbasvir in HIV/HCV G1 or G4, TX-naive

ARVs: Edurant, Tivicay, Isentress + nucleosides/tides

Rockstroh et al; EASL 2015 ACCESS OVERVIEW • Benefits of HCV cure

• US HCV treatment guidelines

• HCV Treatment Access: Myths and Facts

• DAAs: pricing versus cost WHY being cured matters People feel better (duh)

• Uncured HCV can cause systemic health problems • Being cured lowers: • risk of liver-related illness or death—also true for people w/ cirrhosis, HIV/HCV • risk of death from all causes—also true for people w/ cirrhosis, HIV/HCV • risk of AIDS-related illness or death for HIV+ people

Adiolfi, et al; W J Gast 2015; Berenguer, et al; JAIDS 2012; Berenguer, et al; CID 2012; Branch, et al; CID 2012; Cacoub et al; Dig Liver Dis 2014 Mira et al; CID 2013 WHY being cured matters

• increases health care costs and hospitalization rates –even in people who do not have serious liver damage

• Being cured lowers health care utilization and costs

Mc Adam-Marx et al; J Mang Care Pharm; Manos et al; J Mang Care Pharm 2013; McCombs et al; Clin Ther 2011 HCV Treatment Guidelines "The goal of treatment… is to reduce all- cause mortality and liver-related health adverse consequence… by the achievement of virologic cure.”

“Treatment is recommended for patients with chronic HCV .”

AASLD/IDSA Recommendations for Testing, Managing and Treating HCV HCV Treatment Access Myths and Facts Trouble started with….. “Based on available resources, immediate treatment should be prioritized as necessary so that patients at high risk for liver-related complications and severe extrahepatic hepatitis C complications are given high priority.”

AASLD/IDSA Recommendations for Testing, Managing and Treating HCV 2014 State Medicaid Programs: Sofosbuvir Access, by Fibrosis Stage

F3 and F4 ONLY: 30/42

NO FIBROSIS-BASED RESTRICTION: 8 /42 (Alabama, Massachusetts, Minnesota, Mississippi, North Carolina, Nevada, Utah, and Wyoming)

Barua et al; Ann Inter Med 2015 Sofosbuvir: State Medicaid Eligibility, by Fibrosis Stage

Barua et al; Ann Inter Med 2015 Myth: Prioritizing Fact: Rationing We are waiting too long to treat people • Health, QoL compromised • A cure is less likely • Risk for HCC remains • Early treatment > effective

Doctors deserve a chance to cure people! What message are we sending?

Would we tell an HIV+ person that they had to wait to develop AIDS before they could be treated? MYTH: STAMPEDE! Everyone w/ HCV in the US will storm health care systems, demanding immediate treatment FACT: First, You Need to Know if You Have HCV

In the US, 45% to 85% of people with hepatitis C have not been diagnosed

Smith et al; Ann Intern Med 2012 Myth: People who inject drugs should not be treated for HCV— unless they have already stopped doing so for a while • bias about adherence

• lack of data from DAA clinical trials creates vicious cycle

• concerns about reinfection OF NEW OCCUR 80% AMONG CURRENT PWID

PEOPLE LIVING WITH HCV INFECTION Slide Courtesy of Dr Greg Dore, Kirby Institute NSW OF EXISTING INFECTIONS ARE 60% AMONG CURRENT & FORMER PWID

PEOPLE LIVING WITH HCV INFECTION Slide Courtesy of Dr Greg Dore, Kirby Institute NSW Fact: Most HCV cases in the US are from injection drug use Injection drug use is becoming more common among young people

Not everyone wants to or can stop using drugs….and why do they have to?

Do we tell people to quit smoking for 3, 6, or 12 months before they can start chemo? Sofosbuvir: State Medicaid Restrictions for Drug/Alcohol Use 88% (37/42) ask about/ restrict access for drug/alcohol use

21 require drug/alcohol testing as a prerequisite for treatment, for all patients, regardless of history

21 require abstinence (1 - 12 months) for all patients, regardless of history

• 17 ask about, or require treatment for SUDs • 9 require 3 – 6 months of abstinence for people with a history of SUDs

Barua et al; Ann Inter Med 2015 Sofosbuvir: State Medicaid Restrictions for Drug/Alcohol Use

Barua et al; Ann Inter Med 2015 Fact: People who inject drugs can be cured—if they are treated • Who understands consequences of missed doses more?

• There is no evidence base for a specifc duration of abstinence (or one that suggests it should be required)

• People who inject drugs want to be cured

• Cure rates w/ PEG-IFN are similar, whether people inject drugs during TX or not

Aspinall et al; CID 2013; Martin et al; J Viral Hep 2015 Myth: Heavy Drinkers Should not be Treated for HCV Until They are Sober

Fact: there is no evidence to support this

Fact: alcohol use during -based treatment did not lower cure rates

Fact: alcohol accelerates liver damage from HCV --- why force drinkers into developing serious liver disease when it could be prevented?

Anand et al; Gastroenterol 2006; Shoreibah et al; World J Gastroenterol 2014 Sexually Transmitted HCV: The “New” Epidemic Is not new: Outbreaks of sexually transmitted HCV have been reported among non-IDU, HIV+ MSM since 2000 in the UK, Europe, Asia, Australia & the US

A cluster of risk factors are associated with HCV among HIV+ MSM

Bradshaw et al; Curr Opin Infect Dis 2013; van der Lar et al; Gastroenterology 2009 Myth: reinfection risk justifies withholding HCV treatment

Myth: No point in treating PWID and HIV + MSM, because they will just keep getting infected

Fact: Reinfection rates are not high (13% at 5 years for PWID; 1% to 25% for HIV+ MSM)

Fact: Access to prevention (and MSM risk/transmission info) not adequate—leading to reinfection

Fact: curing people is prevention-- the problem is not what people are doing, it’s that we are not treating enough of the people who are at risk

How can we stop this epidemic if we don’t treat and cure people?

Hill et al; CROI 2015 Prevention (and Cure) HCV prevention remains important ---and we need more of it

More information about HIV + MSM and HCV

PaP: prevention as prevention

CasP: Cure as prevention: if you treat enough people, the epidemic will shrink DAAs: pricing versus cost What is excessive?

“If you are making $3 billion/year on (cancer drug) Gleevec, could you get by with $2 billion?

When do you cross the line from essential profits to profiteering?”

Brian Drucker, MD Director, Knight Cancer Institute Myth: HCV treatment is unaffordable

Fact: generic DAAs can be mass- produced—profitably—and sold for a few hundred dollars

Price vs. cost – what factors in?

Hill et al. 20th International AIDS Conference 2014 5g of diamonds 5g of daclatasvir

25 1-carat ($1900 each) 12 weeks of treatment, 60mg/day

Cost = $48,000 Cost = $63,000 (US price)

Slide: Courtesy of Dr. Andrew Hill Daclatasvir: generic prices

Cost of API = $2,000/kg API needed per person = 5g (60mg x 84 days)

API per 12 weeks = $10 Formulation = 40%

Formulated drug = $14 Packaging = $0.35/month

Packaged drug = $15 Profit margin = 50%

Final generic For end 2015, Price = $22 Prices falling rapidly Slide: Courtesy of Dr. Andrew Hill Current costs of sofosbuvir, Per person (12 weeks)

90000 $84,000

80000

70000

60000 $56,000 $53,000 50000

Cost $) (US Cost 40000

30000 $27,000

20000

10000 $7,000

$900 $750 $344 0 USA USA* UK Spain Brazil LMICs Generic Mini

*discount Slide: Courtesy of Dr. Andrew Hill US drug pricing…..

Not the right benchmark, anymore, anywhere…..for anyone.

Myth: AWP is what payers actually spend

Fact: Federal law mandates rebates– of at least 23%-- to State Medicaid programs

They are not paying $84,000 Negotiate! After 20 years in the industry the President of Prime Therapeutics ( >25 million members) “…had never seen prices for a brand-name drug category plummet so quickly after a competing drug was introduced…”

• Gilead is telling investors that the increased number of hepatitis C patients treated can make up any shortfalls from lower net prices, since “….discounts for the treatments.. will more than double this year – to 46%, on average.”

• AbbVie has offered huge discounts in return for exclusivity; signed 25 state deal + 25% to 30% rebate

https://www.primetherapeutics.com/Files/hep_c_agreement_Press_Release__FINAL 1pm.pdf; http://www.wsj.com/articles/states-work-to-strike-deals-for-hep-c-drug-discounts-1422492687add ; http://www.stltoday.com/news/local/govt-and-politics/virginia-young/missouri-to-drop-expensive- hepatitis-c-drug-sovaldi-use-alternative/article_0f2a8964-d4bc-5362-8d41-b10e65d13408.html http://www.thestreet.com/story/13034015/1/gileads-2014-earnings-were-phenomenal-but-the-stock-is- failing-heres-why.html DON’T GIVE UP……