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HCV UPDATE
TREATMENT: WHAT’S NEXTa glimpse of the pharmaceutical pipeline
ACCESS: MYTHS & FACTS current treatment access advocacy
September 2015New York DOHMH
Tracy Swan
HCV Treatment: what’s needed, what’s coming? • Genotype 3 and cirrhosis• Renal impairment• Decompensated cirrhosis, post-transplant• HIV/HCV• Shorter treatment? • Next-generation DAAs
Genotype 3 and Cirrhosis• Globally, 2nd most common: 30%, or 54
million cases
• Higher risk for cirrhosis, liver cancer
• HCV treatment is less effective, especially if treatment-experienced
• Drug resistance is part of the problem
Kanwal et al; rHepatology 2015: Messina et al; Hepatology 2015
ALLY-3: SOF + DAC in G3
Nelson et al; AASLD 2014
G3: Cirrhosis and NS5A Resistance
Some RAVs worse than others
Daklinza presctibing information; Harvoni, prescribing information; http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205834s000lbl.pdf Lindstrom et al; infect Dis 2015
Cure Rate, Y93H
Cure Rate, no Y93H
G3, all 54% (7/13) 92% (124/135)
G3, no cirrhosis 67/% (6/9) 98% (105/107)
G3, cirrhosis 25% (1/4) 68% (19/28)
SOF/GS-5816 ± RBV in G3, TX- experienced, cirrhosis
Pianko et al; AASLD 2014
What to Do?• Add ribavirin: ALLY-3+ , French EAP• Treat longer: ALLY 3+, French EAP• Add a 3rd DAA: Gilead, Merck• Try a different combination (ASTRAL-3)
FRENCH EAP: SOF + Daclatasvir, ± RBV
What we don’t know:
Whether or not people were also given RBV
Effect of RBV versus treatment length
Baseline resistance?
Cure rates in a small group of people were >80%
ASTRAL-3
GS-5816/SOF, 12 weeks 95%
VERSUS
SOF + RBV for 24 weeks 80%
What about people with cirrhosis (30%)?
Gilead Sciences, press release. September 21, 2015
HCV Treatment: Renal Impairment
Higher HCV rate among people with chronic kidney disease (CKD)
Higher HCV rate among dialysis patients; up to 60% in some places
HCV worsens survival in CKD
Azmi et al; W J Hepatol 2015
C-SURFER: Grazoprevir/Elbasvir G1, TX-naive or –experienced, CKD
Roth et al; EASL 2015
RUBY-1: HCV G1, CKD /ESRD
Pockros et al; EASL 2015
HCV Treatment: Decompensated Cirrhosis and Post-Transplant
Averege survival, compensated cirrhosis
>12 years
Averege survival, decompensated cirrhosis
<2 years
Treatment = transplantation, and/or DAAs????
HCV recurs after transplantation unless it is cured first
Zipprich et al; Liver Int 2012
SOLAR-2: Decompensated Cirrhosis and Post-Transplant, G1 and G4
Manns et al; EASL 2015
ALLY-1: Decompensated Cirrhosis and Post-Transplant, all Genotypes
Poordad et al; EASL 2015
Compassionate Use: Decompensated Cirrhosis, Post-Transplant, G 1, 2, 3, 4 ,5
Weizel, et al; EASL 2015
C-SALT: G1, 4 and 6 (dose-finding for CPT Class B)
.Jacobson et l; EASL 2015
Real Life: HCV TARGET, G1, decompensated cirrhosis
Reddy et al; EASL 2015
Real Life:
Real Life: HCV TARGET, G2 and G3, decompensated cirrhosis
Reddy et al; EASL 2015
ASTRAL-4:All Gentoypes, CPT Class B
SOF/GS-5816, 12 weeks: 83% (75/90)
SOF/GS-5816+ RBV, 12 weeks: 94% (82/87)
SOF/GS5816, 24 weeks: 89% (77/90)
Gilead Press Release. September 21, 2015
Less is More • SOF/GS5816 + GS-9857 for 4 or 6
weeks
• Grazoprevir/elbasvir + sofosbuvir for 4, 6 or 8 weeks
• ACH-3102 = sofosbuvir for 6 weeks
Going Shorter: SOF/GS-5816 + GS-9857
Gane et al; .EASL 2015
Going Shorter: Grazoprevir/Elbasvir + SOF in G1
Poordad et al; EASL 2015
Going Shorter: Grazoprevir/Elbasvir + SOF in G3
.Poordad et al; EASL 2015
Going Shorter: ACH-3102 + SOF in G1
Patel et al; EASL 2015
Treating HCV in HIV/HCV• Cure rates are the same, and 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
Grazoprevir/Elbasvir in HIV/HCV G1,4 and 6, HCV TX-naive
Rockstroh et al; EASL 2015
ION-4: sofosbuvir/ledipasvir in HIV/HV, G1 and G4
Cooper et al; IAS 2015
ALLY-2: sofosbuvir/daclatasvir in HIV/HCV, TX-naive or experienced G1, 2, 3,4
Wyles et al; CROI 2015
Son(s) of Sofosbuvir
PRECLINICAL:
AL-516 (Janssen) and MIV-802 (Medivir)
PHASE I
AL-335(Janssen)
PHASE II
ACH-3422 (Achillon/Janssen), MK-3682 (Merck)
2nd Generation, in Phase 2
NS5a inhibitors
ABT-530
ACH-3102
MK-8408
Protease inhibitors
ABT-493
GS-9857
2016 DAAs
Grazoprevir/Elbasvir FDC (g1, 4 and 6)
Studied in tx-naive, DAA treatment-experienced, HIV/HCV, CKD, decompnsated cirrhosis, PWID
Sofosbuvir/Velpatsvir FDC (all genotypes)
Studied in all HCV genotypes, TX-naive or experneicd, decompensated cirrhosis
ACCESS OVERVIEW• Benefits of HCV cure • US HCV treatment guidelines • HCV Treatment: 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
• Hepatitis C 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 infection.”
AASLD/IDSA Recommendations for Testing, Managing and Treating HCV
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
HCV Treatment Access Myths and Facts
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
Smith et al; Ann Intern Med 2012
In the US, 45% to 85% of people with hepatitis C have not been diagnosed
Myth: mentally ill people are not good candidates for HCV TXFact: people with mental illness have been successfully—and safely—treated, even with peginterferon and ribavirin
Fact: these criteria are relics from ye olde interferon-based treatment era, if people are used to taking psych meds, they can certainly take DAAs
Fact: hepatitis C can cause depression—why withhold treatment that may improve it?
Hilsabeck et al; Hepatol 2002; Mustafa et al; J Viral Hep 2014; Schaefer, et al: CID 2013 Tong; Spradling; J Viral Hep 2015
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
80% OF NEW INFECTIONS OCCUR AMONG CURRENT PWID
PEOPLE LIVING WITH HCV INFECTION
Slide Courtesy of Dr Greg Dore, Kirby Institute NSW
60% OF EXISTING INFECTIONS ARE AMONG CURRENT & FORMER PWID
PEOPLE LIVING WITH HCV INFECTIONSlide 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?
Fact: People who inject drugs can be cured—if they are treated
• Who understands consequences of missed doses more?
• There is no evicdence 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
Sexually Transmitted HCV: The “New” EpidemicIs 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 treatmentNo 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 $2 billion? When do you cross the line from essential profits to profiteering?”
Brian Drucker, MD
Director, Knight Cancer Institute
Myth: HCV treatment is unaffordable
Fact: generic DAAs can be mass-
produced—profitably—and sold for a few hundred dollars
A “package” of HCV diagnostics and treatment could be available in LMICs for < US$ 400
Hill et al. 20th International AIDS Conference 2014
US launch price vs. (mass) production cost: 12 weeks of Sovaldi ($84,000 vs. $121) or Harvoni ( $94,500 vs. $192)
SOF SOF/LDV78000
80000
82000
84000
86000
88000
90000
92000
94000
96000
Hill et al; 20th International AIDS Conference 2014; Van de Ven et al; Hepatol 2015
US drug pricing…..
Not the right benchmark, anymore, anywhere…..for anyone.
Myth: AWP is what payers actually spend
Fact: Federal law mandates rebates--at least 23%-- to to State Medicaid programs
They are not paying $84,000
Negotiate!“It was clear that neither Gilead nor AbbVie wanted to be left off our formulary… the result proved to be significantly better than taking an exclusive position.” - Peter Wickersham, Senior Vice President of Integrated Care and Specialty, Prime– > 25 million members.
• Gilead is telling investors that the increased number of hepatitis C patients treated can make up any shortfalls from lower net prices
• 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
Competition = prices
in his 20 years in the industry, Peter Wickersham
“…had never seen prices for a brand-name drug
category plummet so quickly after a competing
drug was introduced…
“….discounts for the treatments.. will more than
double this year – to 46%, on average.” http://www.thestreet.com/story/13034015/1/gileads-2014-earnings-were-phenomenal-but-the-stock-is-failing-heres-why.html
Access in New York State
The New York State Hepatitis C Coalition is a diverse group of
community, activist and advocacy organizations, and individuals. We
fight for universal access to high quality hepatitis C virus (HCV) care,
treatment and prevention. We take action to ensure that all people
living with HCV in New York State are tested, diagnosed, and
immediately connected to appropriate medical care and support
services. We demand unrestricted access to affordable curative
treatments. Our mission is to end the hepatitis C epidemic and
eradicate HCV from New York State.
