Prof Aamir Ghafoor Khan FRCP, FRCP (Ed ) FRCP(G) FRCPI(Ire) AGAF(USA) FACG(USA) FACP(USA) MSc (Gastro,UK) FEBG(EU) DGM RCP&S(G) FRSM(UK) President

Transcription

1 Prof Aamir Ghafoor Khan FRCP, FRCP (Ed ) FRCP(G) FRCPI(Ire) AGAF(USA) FACG(USA) FACP(USA) MSc (Gastro,UK) FEBG(EU) DGM RCP&S(G) FRSM(UK) President Pakistan GI & Endoscopy Society. 1

2 Hepatitis C Virus was isolated in 1989; a member of Flaviviridae and is a major pathogen of hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC).* Hepatitis C virus (HCV) was found to be a major cause of non-a non-b (NANB) hepatitis in the world. # ** Kato, 2001; Bhandari and Wright, 1995; Shepard et al., 2005; Giannini and Brechot, 2003). # Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cdna clone derived from blood born non-a, non-b viral hepatitis genome. Science 1989; 244:

3 <1% <2-2.4% < % <5-10% >10% No data available Statistically, as many people are infected with HCV as are with HIV, 3

4 170 Million-200 Million Carriers Worldwide Far East Asia 60 M United States 3-4 M Western Europe 5 M Americas M Africa M Eastern Europe 10 M Southeast Asia M Australia 0.2 M M=million 4

5 The disease is becoming a major health problem of developing countries, including Pakistan that has the second highest prevalence rate of hepatitis C ranging from 4.5% to 8%. * *Khattak MF, Salamat N, Bhatti FA, Qureshi TZ. Seroprevalence of hepatitis B, C and HIV in blood donors in northern Pakistan. J Pak Med Assoc. 2002; 52:

6 Studies in Pakistan on small targeted groups including blood donors, health professionals, drug abusers and chronic liver disease patients indicate that the prevalence of hepatitis C is as high as 40%.* *Abbas Z, Jeswani NL, Kakepoto GN, Islam M, Mehdi K, Jafri W. Prevalence and mode of spread of hepatitis B and C in rural Sindh, Pakistan. Trop Gastroenterol. 2008; 29:

7 30 25 % HCV +ve % HCV +ve Islamabad Rawalpindi Multan Faisalabad Karachi Mardan Buner Northern Areas (Farhana et al., 2009; Chaudhary et al., 2007; Jehangir et al., 2006; Hashmie et al., 1999; Kazmi et al., 1997; Khan et al.,2004; Muhammad and Jan, 2005; Tariq et al., 1999). 7

8 Several studies indicate that the rate of positivity for HCV is much higher in rural areas than the peri-urban areas of Pakistan. It is worrisome to note that 66% population of Pakistan is living in the rural areas. Noureen Jiwani, Dr. Raisa Gul. A Silent Storm: Hepatitis C in Pakistan.Journal of pioneering medical sciences:volume 1, Issue

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10 Sindh Punjab NWFP Balochistan HBsAg +ve 2.5% 2.4% 1.3% 4.3% HCV +ve 5.0% 6.7% 1.1% 1.5% Both +ve 0.2% 0.2% 0.1% 0.1% All Negative 8212 (92.2%) (90.7%) 7446 (97.5%) 4981 (94.1%) Prevalence of Hepatitis B and C in General Population of Pakistan By Pakistan Medical Research Council, Islamabad in the Year

11 Province NWFP No. of persons Screened HCV No % Total Population (2004) Affected Population (Approximately) Tank ,000 1,000 Chitral ,000 1,000 Abbottabad ,016, Dera Ismail Khan , Haripur , Shangla , Karak , Upper Dir , NWFP 7, ,872, ,000 Prevalence of Hepatitis B and C in General Population of Pakistan By Pakistan Medical Research Council, Islamabad in the Year

12 Province Punjab No. of persons Screened HCV No % Total Population (2004) Affected Population (Approximately) Vehari ,373, ,000 Hafizabad , ,000 Pakpattan ,460, ,000 Bahawalnagar ,340, ,000 Bahawalpur ,761, ,000 Okara ,534, ,000 Shekhupura 1, ,769, ,000 Jhang ,217, ,000 Faisalabad 1, ,162, ,000 Multan 1, ,537, ,000 Rawalpindi 1, ,818, ,000 T.T. Singh ,841, ,000 Sahiwal ,092, ,000 Sialkot 1, ,091, ,000 Lahore 1, ,171, ,000 Lodhran ,330,000 89,000 Attock ,447,000 96,000 12

13 District of Balochistan Province No. of persons Screened HCV No % Total Population (2004) Affected Population (Approximately) Musa Khel ,000 8,000 Jaffarabad ,000 26,000 Barkhan ,000 5,000 Zhob ,000 12,000 Loralai ,000 11,000 Nasirabad/Tamboo ,000 8,000 Mastung ,000 4,000 Quetta ,000 14,000 Awaran ,000 2,000 Lasbela ,000 4,000 Khuzdar ,000 6,000 Pishin ,000 3,000 Kohlu ,000 1,000 Prevalence of Hepatitis B and C in General Population of Pakistan By Pakistan Medical Research Council, Islamabad in the Year

14 A study showed that in Pakistan more than 90% of HCV positive subjects were unaware of HCV infection in general (Idrees et al., 2008). 14

15 Multiple use of needles/ syringes = 61.45% Major/minor surgery/dental procedures = 10.62% Blood transfusion and blood products = 4.26% Sharing razors during shaving or circumcision by barbers = 3.90% Piercing instruments, nail clippers, tooth brushes, due to needle stick, from infected mother to baby and sexual transmission < 1% The mode of transmission is unclear = 20.35% (Farhana et al., 2009; Idrees et al., 2008; Idrees and Riazuddin, 2008) 15

16 Sales Injection drug use Sexual Transfusion (before screening) Other (hemodialysis; health care work; perinatal) Unknown 10% 15% 5% 10% 60% 16

17 Several studies from Pakistan showed that the average number of injections per person per year is more than 13 injections in this country that is one of the highest frequencies of injections anywhere in the world (Jafri et al. 2006; Khan et al.2000). 17

18 The Ministry of Health Government of Pakistan has published a survey in year 2002 that shows that in Pakistan more than 72% therapeutic injections and 50% immunization injections in public health-care facilities are unsafe and potentially dangerous for the spread of infections including HCV. 18

19 Province No. of Subject Number of Injections < More than 10 Sindh 8, % 34.4% 5.9% Punjab 25, % 17.8% 5.1% NWFP 7, % 25.0% 10.0% Balochistan 5, % 21.8% 6.9% Total 47, % 22.6% 6.2% Prevalence of Hepatitis B and C in General Population of Pakistan By Pakistan Medical Research Council, Islamabad in the Year

20 WHO allows 3.5 injections/person/year WHO study showed Pakistan has 13.6 injection/person/year AKU and PMRC studies showed 13&14 inj Pakistan has the highest therapeutic use of injectables world wide The higher the injection usage the more is chance of blood born infections i.e. Hepatitis etc. 20

21 Interferon therapy Interferon Free therapy 21

22 Genotype Recommended Alternative NOT Recommended 1 IFN eligible: SOF + PEG/RBV x 12 weeks IFN ineligible: SOF + SMV ± RBV x 12 weeks 2 SOF + RBV x 12 weeks None 3 SOF + RBV x 24 weeks 4 5 or 6 IFN eligible: SOF + PEG/RBV x 12 weeks IFN ineligible: SOF + RBV x 24 weeks SOF + PEG/RBV x 12 weeks IFN eligible: SMV x 12 weeks + PEG/RBV x 24 weeks IFN ineligible: SOF + RBV x 24 weeks SOF + PEG/RBV x 12 weeks SMV x 12 weeks + PEG/RBV x weeks PEG/RBV X 48 weeks TVR + PEG/RBV x 24 or 48 weeks (RGT) BOC + PEG/RBV x 28 or 48 weeks (RGT) PEG/RBV x 48 weeks Monotherapy with PEG, RBV, or a DAA. Do not treat decompensated cirrhosis with PEG or SMV PEG/RBV x 24 weeks Monotherapy with PEG, RBV, or a DAA Any regimen with TVR, BOC, or SMV PEG/RBV x weeks Monotherapy with PEG, RBV, or a DAA Any regimen with TVR, BOC, or SMV PEG/RBV x 48 weeks Monotherapy with PEG, RBV, or a DAA Any regimen with TVR or BOC Monotherapy with PEG, RBV, or a DAA Any regimen with TVR or BOC For genotype 1a. Baseline resistance testing for Q80K should be performed and alternative treatments considered if this mutation is present. 22

23 Estimated cost of universal treatment of all patient in Pakistan is Rs billion (NIH estimate 05) The cheapest course currently for six month is Rs. 60,000 ($600) that does not include cost of tests, hospital stay etc. 23

24 S.No Duration Number of patients Yes ETR No 1 Sept-2011 to December , Jan-2013 to Sept Feb Total 2,056 1,197 (58.21%) 859 (41.78%) 24

25 S.No Duration Number of patients Yes ETR No 1 July till date (64.9%) 128 (35.06%) 25

26 Achieved Not Achieved ETR

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28 Designated as a Breakthrough Product by the FDA Approved by the USFDA on Fast track in December 2013 European Priority Approval in January 2014 Cost in the US: $84,000 for 3 months in Genotype 1 Translates to $168,000 for Genotype 3 Patients 28

29 Filing Plan Announced at EASL in April 2014 Dossier Filed for DRAP Approval in May 2014 Discussed for Registration in July 2014 Ostensibly Approved by the Drugs Registration Board (DRB) in August Issuance of Registration Still Pending finalization of DRB minutes and subsequent Pricing Finalization Commitment to provide drug at $300 for Supply to Access Agencies such as Government Programs and Verified NGO s 29

30 Despite delayed approval/regulatory challenges, access through Named Patient Assistance has been granted by the Drug Regulatory Authority (DRAP). Over 3,200 patients named-patient applications received so far under the program. 1,100 approvals received. First set of 500 patients started receiving Treatment end- August Potential to Create one of the World s largest Real World DAA Registries Ferozsons has developed an Androidbased registry system to be used for clinical management postapproval. 30

31 Restricted Availability until Regulatory Approval. Parallel Trade Efforts may Undermine Access. Suboptimal Treatments may create resistance. Treatment Guidelines Needed to Ensure optimal treatment outcomes, and to guide government programs for HCV Treatment and Control. 31

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