Tenofovir Disoproxil Fumarate, tablet 300 mg, Viread®, November 2008
Public Summary Document for tenofovir disoproxil fumarate, tablets 300mg, Viread®
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Public Summary Document
Product: Tenofovir Disoproxil Fumarate, tablet 300
mg, Viread®
Sponsor: Gilead Sciences Pty Ltd
Date of PBAC Consideration: November 2008
1. Purpose of Application
The submission sought to extend the current Section 100 (Highly
Specialised Drug) listing to include treatment of chronic hepatitis
B (CHB).
Highly Specialised Drugs are medicines for the treatment of chronic
conditions, which, because of their clinical use or other special
features, are restricted to supply to public and private hospitals
having access to appropriate specialist facilities.
2. Background
At its June 2002 meeting, the PBAC recommended listing of tenofovir
under Section 100 for treatment in combination with other
anti-retroviral drugs, of HIV infection in patients who have failed
or experienced treatment-limiting toxicity with their current
antiretroviral regimen and for whom a variable regimen cannot be
constructed from other classes of anti-retroviral agents.
At its November 2004 meeting, the PBAC recommended extending the
listing of tenofovir to that of other nucleoside reverse
transcriptase inhibitors (NRTIs) listed on the PBS.
Tenofovir had not previously been considered by the PBAC for the
treatment of CHB.
3. Registration Status
Tenofovir was first registered by the TGA on 13 August 2002 and is
indicated for use in combination with other retroviral agents for
the treatment of HIV-infected adults. Evidence to support this
indication is based on analyses of plasma HIV-1 RNA levels and CD4
cell counts in controlled studies of tenofovir in
treatment-naïve adults and in treatment-experienced adults. In
July 2008, the TGA approved indications were extended to include
treatment of CHB in adults with evidence of active viral
replication and active liver inflammation.
4. Listing Requested and PBAC’s View
Section 100 – Highly Specialised Drugs Program
Private hospital authority required.
Treatment of HIV infection in patients with:
a. CD4 cell counts of less than 500 per cubic millimetre; or
b. Viral load of greater than 10,000 copies per mL.
Treatment-naïve chronic hepatitis B patients who satisfy all of the following criteria:
- Histological evidence of chronic hepatitis on liver biopsy (except in patient for whom a liver biopsy is contraindicated);
- Abnormal serum ALT levels and / or elevated HBV DNA in conjunction with documented chronic hepatitis B infection.
Chronic hepatitis B in patients who have failed antihepadnaviral therapy and who satisfy all of the following criteria:
- Repeatedly elevated serum ALT levels despite antihepadnaviral therapy of greater than or equal to 6 months duration with documented chronic hepatitis B infection or;
- Persistently elevated HBV DNA levels despite prior antihepadnaviral therapy of greater than or equal to 6 months duration or failure to achieve a 1 log reduction in HBV DNA within 3 months of commencing antihepadnaviral therapy except in patients with evidence of poor compliance.
NOTE:
Patients who have failed prior antihepadnaviral therapy may receive tenofovir treatment
in combination with lamivudine.
Patients should have undergone a liver biopsy at some point since initial diagnosis
to obtain histological evidence of chronic hepatitis.
Persons with Child’s class B or C cirrhosis (ascites, variceal bleeding, encephalopathy,
albumin less than 30 g per L, bilirubin greater than 30 micromoles per L) should have
their treatment discussed with a transplant unit prior to initiating therapy.
Female patients who are of child-bearing age should not be pregnant, should not be
breast-feeding, and should be using an effective form of contraception.
For PBAC’s view, see Recommendation and Reasons.
5. Clinical Place for the Proposed Therapy
Tenofovir would provide an alternative oral treatment for chronic
hepatitis B in both treatment naïve and treatment experienced
patients.
6. Comparator
The submission nominated entecavir monohydrate 0.5 mg for
nucleos(t)ide naïve patients, and adefovir dipivoxil 10 mg for
nucleos(t)ide experienced patients. These were considered
appropriate by PBAC.
7. Clinical Trials
Nucleos(t)ide naïve patients
The basis of the submission for tenofovir in nucleos(t)ide
naïve patients was an adjusted indirect comparison (An
adjusted indirect comparison is one in which the indirect
comparison of intervention B and C is adjusted by the results of
their direct comparisons with a common intervention. Song F, Altman
D, et al Validity of indirect comparison for estimating
efficacy of competing interventions: empirical evidence from
published meta-analyses. BMJ 2003; 326: 472.) of one
randomised trial of tenofovir 300 mg and one randomised trial of
entecavir 0.5mg, with adefovir 10mg as the common reference, for
hepatitis B e antigen (HBeAg) positive patients over 48 weeks; an
unadjusted indirect comparison of the tenofovir 300mg arm of a
randomised trial in HBeAg positive patients and the tenofovir 300mg
arm of a randomised trial in HBeAg negative patients; and an
unadjusted indirect comparison of the entecavir 0.5mg arm of a
randomised trial in HBeAg positive patients and the entecavir 0.5mg
arm of a randomised trial in HBeAg negative patients. Details of
the studies published at the time of the submission are presented
in the table below.
Trials and studies presented in the submission –
nucleos(t)ide naïve patients
| Trial ID/ Author | Protocol title/ Publication title | Publication citation |
| Indirect comparison in HBeAg positive patients – common reference adefovir | ||
| Tenofovir | ||
| 0103 HBeAg positive patients | GS-US-174-0103. A randomised double-blind, controlled evaluation of tenofovir DF versus adefovir dipivoxil for the treatment of HBeAg positive chronic hepatitis B. | Report date: August 2007 http://www.clinicaltrials.gov/ct2/show/NCT00116805?term=GS-US-174-0103&rank=1 |
| Entecavir | ||
| Leung 2007 HBeAg positive patients | Entecavir results in higher HBV DNA reduction versus adefovir in chronically infected HBeAg positive antiviral-naïve adults: 48 week results (EARLY study). | Leung, N et al. 42nd Annual Meeting of the European Association for the Study of the Liver (2007). |
| Entecavir results in higher HBV DNA reduction vs. adefovir in chronically infected HBEAG (plus) antiviral-naïve adult: 24 wk results (EARLY study). | Leung N, Peng C, Sollano J, Lesmana L, Yuen MF, Jeffers L, et al. Hepatology 2006; 44: 554A | |
| Entecavir results in higher HBV DNA reduction versus adefovir in antiviral-naïve HBeAg(+) adults with high HBV DNA: week 96 results (EARLY study). | Leung N, Peng CY, Sollano J, Lesmana L, Yuen MF, Jeffers L, et al. 43rd Meeting of the European Association for the Study of the Liver (2008). | |
| Naïve indirect comparison between HBeAg positive and HBeAg negative patients | ||
| Tenofovir | ||
| 0102 HBeAg negative patients | GS-US-174-0102. A randomised, double-blind, controlled evaluation of tenofovir DF versus adefovir dipivoxil for the treatment of presumed pre-core mutant chronic hepatitis B. | Report date: August 2007 http://www.clinicaltrials.gov/ct2/results?term=GS-US-174-0102 |
| 0103 HBeAg positive patients | GS-US-174-0103. A randomised double-blind, controlled evaluation of tenofovir DF versus adefovir dipivoxil for the treatment of HBeAg positive chronic hepatitis B. | Report date: August 2007 http://www.clinicaltrials.gov/ct2/results?term=GS-US-174-0103 |
| Entecavir | ||
| Chang 2006 HBeAg positive patients | A comparison of entecavir and lamivudine for HBeAg positive chronic hepatitis B. | Chang T, Gish R, de Man R, Gadano A, Sollano J, Chao Y, et al. New Engl J Med 2006; 354: 1001–1010. |
| Entecavir is superior to lamivudine for the treatment of HBeAg(+) chronic hepatitis B: results of phase III study ETV- 022 in nucleoside-naïve patients. | Chang T, Gish R, de Man R, Gadano A, Sollano J, Han K, et al. Hepatol 2004; 40: 193A. | |
| Entecavir therapy for up to 96 weeks in patients with HBeAg positive chronic hepatitis B. | Gish R, Lok A, Chang T, de Man R, Gadano A, Sollano J, et al. Gastroenterol 2007; 133: 1437–1444 | |
| Lai 2006 HBeAg negative patients | Entecavir versus lamivudine for patients with HBeAg negative chronic hepatitis B. | Lai C, Shouval D, Lok A, Chang T, Cheinquer H, Goodman Z, et al. New Engl Med 2006; 354: 1011–1020. |
DF=disoproxil fumarate; DNA= deoxyribonucleic acid; HBeAg and
HBEAG=hepatitis B e antigen; HBV=hepatitis B virus; HIV=human
immunodeficiency virus.
Nucleos(t)ide experienced patients
The basis of the submission for tenofovir in nucleos(t)ide
experienced patients was a comparison of tenofovir 300mg and
adefovir 10mg using the combined subgroups of experienced patients
from two direct randomised trials, the first in HBeAg positive
patients and the second in HBeAg negative patients. Conventional
meta-analytic techniques were not used for this comparison.
Supportive trials include one randomised trial comparing tenofovir
monotherapy with tenofovir/emtricitabine combination therapy; an
open label study of tenofovir/lamivudine combination therapy in
patients with lamivudine resistance and suboptimal response to
adefovir; one small randomised trial comparing tenofovir with
adefovir in patients co-infected with human immunodeficiency virus
(HIV) and hepatitis B virus (HBV); and one study comparing
tenofovir/lamivudine combination therapy with lamivudine
monotherapy in HIV/HBV co-infected patients. Details are presented
in the table below.
Trials and studies presented in the submission –
nucleos(t)ide experienced patients.
| Trial ID/ Author | Protocol title / Publication title | Publication citation |
| 0102 (subgroup) HBeAg negative patients combined with | GS-US-174-0102. A randomised, double-blind, controlled evaluation of tenofovir DF versus adefovir dipivoxil for the treatment of presumed pre-core mutant chronic hepatitis B. | Report date: August 2007 http://www.clinicaltrials.gov/ct2/results?term=GS-US-174-0102 |
| 0103 (subgroup) HBeAg positive patients | GS-US-174-0103. A randomised double-blind, controlled evaluation of tenofovir DF versus adefovir dipivoxil for the treatment of HBeAg positive chronic hepatitis B. | Report date: August 2007 http://www.clinicaltrials.gov/ct2/results?term=GS-US-174-0103 |
| 0106 HBeAg positive patients and HBeAg negative patients | GS-US-174-0106. A phase 2, randomised, double-blind study exploring the efficacy, safety and tolerability of tenofovir disoproxil fumarate (DF) monotherapy versus emtricitabine plus tenofovir DF fixed-dose combination therapy in subjects currently being treated with adefovir dipivoxil for chronic hepatitis B and having persistent viral replication. | Report date: August 2007. http://www.clinicaltrials.gov/ct2/results?term=GS-US-174-0106 |
| 0109 HBeAg positive patients and HBeAg negative patients | IN-AU-174-0109. An open label study evaluating the antiviral activity of tenofovir DF 300mg daily in patients with chronic hepatitis B infection and persistent viral replication after long-term therapy with adefovir dipivoxil 10mg daily. | Protocol date: 10 May 2006. |
| A prospective study of tenofovir disoproxil fumarate for patients with chronic hepatitis B who have previously failed lamivudine and have persistent viral replication despite at least 24 weeks of adefovir therapy. | Patterson S, Lee A, Strasser S, Desmond P, Roberts S, Angus P, et al. Unpublished. | |
| Dore 2004 (substudy 903) HBeAg positive patients and HBeAg negative patients | Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naïve and –experienced patients co-infected with HIV-1 and hepatitis B virus. | Dore G, Cooper D, Pozniak A, DeJesus E, Zhong L, Miller M, et al. J Infect Dis 2004; 189: 1185–1192. |
| Peters 2006 HBeAg positive patients and HBeAg negative patients | Randomised controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127. | Peters M, Andersen J, Lynch P, Liu T, Alston-Smith B, Brosgart C, et al , for the ACTG Protocol A5127 Team. Hepatol 2006; 44: 1110–1116. |
ACTG=Adult AIDS Clinical Trials Group; DF=disoproxil fumarate; DNA=
deoxyribonucleic acid; HBeAg=hepatitis B e antigen; HBV=hepatitis B
virus; HIV=human immunodeficiency virus.
8. Results of Trials
1) Nucleos(t)ide naïve patients
The submission aimed to demonstrate the non-inferiority of tenofovir 300mg to entecavir
0.5mg. The submission argued that the following chain of logic leads to the conclusion
that tenofovir is non-inferior to entecavir 0.5mg in both HBeAg positive and HBeAg negative patients:
1. Tenofovir is non-inferior to entecavir 0.5mg in HBeAg positive CHB patients. The evidence presented was an adjusted indirect comparison of tenofovir and entecavir
from one randomised trial of tenofovir in HBeAg positive patients (0103) and one randomised
trial of entecavir 0.5mg in HBeAg positive patients (Leung 2007). The common reference
for this indirect comparison was adefovir.
Summary of results of the indirect comparison of tenofovir versus entecavir in nucleos(t)ide-naïve, HBeAg positive patients
| 0103 | Leung 2007 | Adjusted indirect estimate of effect (95%CI) | |||||
| HBV <300 copies/mL | Treatment effect a (95% CI) | Tenofovir n/N (%) | ADV n/N (%) | ADV n/N (%) | Entecavir n/N (%) | Treatment effect b (95% CI) | |
| Relative risk Odds ratio c | 6.04 (3.45,10.6) 20.30 (9.93,41.5) | 130/176 (74) | 11/90 (12) | 6/32 (19) | 19/33 (58) | 3.07 (1.41,6.69) 5.88 (1.91,18.1) | 1.97 (0.75,5.14) 3.45 (0.91,13.1) |
ADV=adefovir; CI, confidence interval; n, number of participants reporting data; N,
total participants in group, RR, relative risk
a Tenofovir over adefovir
b Entecavir over adefovir
c Calculated during the evaluationThe submission stated that no significant difference was detected between patients
treated with tenofovir (74%) and patients treated with entecavir (58%). A non-inferiority
margin was not specified. The width of the adjusted confidence interval strongly suggested
that this comparison was underpowered.
Due to the lack of a study allowing a common comparator the following logic was applied
for comparison to entecavir in HBeAg negative CHB.
2. Tenofovir has similar efficacy in both HBeAg positive and HBeAg negative CHB patients. The basis of this argument was an unadjusted comparison of the tenofovir treatment
arms from trials 0102 and 0103 without use of a common reference.
3. Entecavir has similar efficacy in both HBeAg positive and HBeAg negative CHB patients. The basis of this argument was an unadjusted comparison of the entecavir treatment
arms from trials Chang 2006 and Lai 2006 without use of a common reference.
4. From points 2-3, it is claimed that tenofovir is also non-inferior to entecavir
in HBeAg negative CHB patients.
The results of the unadjusted indirect comparison that were intended to demonstrate
equivalent efficacy of firstly tenofovir (point 2 above), and secondly entecavir (point
3 above), in HBeAg positive versus HBeAg negative patients are presented in the following
tables.
Summary of the main results of the unadjusted indirect comparison without a common
reference of tenofovir in HBeAg positive patients versus HBeAg negative patients-
nucleos(t)ide naive
| 0102 HBeAg negative | 0103 HBeAg positive | |||
| Outcome | Tenofovir n / N (%) | Tenofovir n / N (%) | OR a (95% CI) | p-value b |
| Complete response | 177/250 (70.8) | 117/176 (66.5) | 1.22 (0.81, 1.85) | 0.34 |
| HBV DNA <300 Copies/mL | 236/250 (92.0) | 130/176 (73.9) | 5.28 (2.78, 10.03) | <0.001 |
CI = confidence interval; n = number with event; N = number in group; OR = odds ratio
a Calculated during the evaluation
b Comparison of tenofovir HBeAg positive and tenofovir HBeAg negative
Underlined
text indicates primary outcome measure
Summary of the main results of the unadjusted indirect comparison without a common
reference of entecavir in HBeAg positive patients versus HBeAg negative patients –nucleos(t)ide
naïve patients.
| Lai 2006 HBeAg negative | Chang 2006 HBeAg positive | |||
| Outcome | Entecavir n / N (%) | Entecavir n / N (%) | OR a (95% CI) | p-value b |
| Histologic response | 208/296 (70) | 226/314 (72) | 0.92 (0.65, 1.31) | 0.64 |
| HBV DNA <300 copies/mL | 293/325 (90) | 236/354 (67) | 4.58 (2.99, 7.01) | <0.001 |
CI=confidence interval; LMV=lamivudine n = number with event; N = number in group; OR=odds ratio
aCalculated during the evaluation
b Comparison of entecavir HBeAg positive and entecavir HBeAg negative
Underlined text indicates primary outcome measure
The claim that tenofovir is equally effective in HBeAg negative and HBeAg positive
patients, and the similar claim for entecavir, were based on the p-values for the
respective primary outcomes of each of the unadjusted indirect comparisons, and no
statistically significant difference between the relevant patient groups for the primary
outcomes of the different trials.
For PBAC’s comments on these results, see Recommendation and Reasons.
2) Nucleos(t)ide experienced patients
The submission aimed to demonstrate non-inferiority of tenofovir 300mg to adefovir
10mg.
The key evidence presented to support the requested listing of tenofovir for treatment
of CHB in nucleos(t)ide experienced patients was a direct comparison of tenofovir
and adefovir using the combined results for the subgroups of experienced patients from single arms of two randomised controlled trials (RCTs),
one in HBeAg positive patients and one in HBeAg negative patients.
Summary of results of the direct comparison of tenofovir versus adefovir in nucleos(t)ide-experienced
patients (combined analysis from studies 0102 and 0103)
| Outcome | Tenofovir n/N (%) | Adefovir n/N (%) | RR a (95% CI) | OR a (95% CI) | p-value |
| Complete response | 37/51 (72.5) | 15/24 (62.5) | 1.16 (0.82, 1.65) | 1.59 (0.57, 4.44) | 0.390 |
| HBV DNA <400 copies/mL | 46/51 (90.2) | 17/24 (70.8) | 1.27 (0.9, 1.67) | 3.79 (1.06,13.56) | 0.057 (0.068) |
| Histologic response | 40/51 (78.4) | 21/24 (87.5) | 0.90 (0.73, 1.10) | 0.52 (0.13, 2.07) | 0.307 |
CI=confidence interval; DNA=deoxyribonucleic acid; HBV=hepatitis B virus; n = number with event;
N = number in group; OR=odds ratio
a Calculated during the evaluation
For PBAC’s comments on these results, see Recommendation and Reasons.
Direct comparative safety data on tenofovir versus entecavir in nucleos(t)ide naïve
patients were not presented in the submission. The majority of the comparative safety
data for tenofovir versus adefovir was from the two key RCTs in predominantly treatment naïve patients. The PBAC noted that overall, the frequencies of adverse events were similar
for tenofovir and adefovir, with the exception of nausea, which occurred more often
in the tenofovir treatment group. The most frequently occurring adverse events were
headache, nasopharyngitis, and back pain. Grade 3 or 4 adverse events, serious adverse
events and adverse events resulting in permanent discontinuation or interruption of
study drug were all infrequent and occurred at similar rates in both groups. No adverse
event led to discontinuation in more than one subject. The safety profile of tenofovir
in CHB patients was consistent with the known safety profile of tenofovir in patient
with HIV infection.
9. Clinical Claim
The submission described tenofovir as non-inferior in terms of
comparative effectiveness and non-inferior in terms of comparative
safety to entecavir 0.5mg in nucleos(t)ide naïve patients, and
to adefovir in nucleos(t)ide experienced patients.
The PBAC accepted the claim of non-inferiority of tenofovir to
entecavir 0.5 mg in HBeAg positive CHB nucleoside naïve
patients. Based on the data provided, the Committee did not accept
the claim that tenofovir is equally effective in nucleoside
naïve HBeAg negative and HBeAg positive patients, or the
similar claim for entecavir.
10. Economic Analysis
The submission presented a cost minimisation analysis. The
equi-effective doses of tenofovir 300 mg per day and entecavir 0.5
mg per day were accepted by the PBAC for the treatment of HBeAg
positive nucleoside naïve patients. Because non-inferiority
had not been established beyond reasonable doubt (see above), the
claim of equi-effectiveness at these doses for the other requested
listings is not supportable.
11. Estimated PBS Usage and Financial Implications
The submission estimated the likely number of patients per year to be less than 10,000
in Year 5. The PBAC considered that the estimate was likely an overestimate.
The submission estimated financial savings per year to the PBS of less than $10 million in Year 5. The submission’s estimate
is a combined cost for nucleos(t)ide naïve and experienced patients.
The submission estimated the financial cost per year to the PBS in nucleos(t)ide naïve patients to be less than $10 million in
Year 5.
The submission estimated the financial savings per year to the PBS in nucleos(t)ide experienced patients at less than $10 million
in Year 5.
12. Recommendation and Reasons
The PBAC recommended the listing of tenofovir on the S100 Highly Specialised Drugs
Program of the PBS for the treatment patients with HBeAg-positive chronic hepatitis
B (CHB) who are nucleoside analogue naïve on a cost minimisation basis to entecavir
0.5 mg tablets. The equi-effective doses in this indication are tenofovir 300 mg per
day and entecavir 0.5 mg per day. The Committee also recommended that a new total
expenditure cap should be developed for tenofovir to manage the possibility of use
outside the PBS indication.
In making this recommendation the Committee agreed that the comparators entecavir
monohydrate 0.5 mg for patients naïve to nucleos(t)ide therapy and adefovir dipivoxil
10 mg for patients who have failed previous nucleos(t)ide therapy were appropriate.
The PBAC further accepted the claim of non-inferiority of tenofovir to entecavir 0.5
mg in HBeAg positive CHB nucleoside naïve patients based on the adjusted indirect
comparison of tenofovir to entecavir presented in the submission from the randomised
trial of tenofovir in HBeAg positive patients (0103) to the randomised trial of entecavir
0.5 mg in HBeAg positive patients (Leung 2007) with the common reference of adefovir.
Although a pre-defined non-inferiority threshold was not specified for the comparison,
the Committee accepted the non-inferiority margin of 10 – 15 % proposed in the pre-Sub-Committee
response.
The Committee did not accept, based on the data provided, the claim that tenofovir
is equally effective in nucleoside naïve HBeAg negative patients to entecavir because
this conclusion relies on the assumption that tenofovir is equally effective in nucleoside
naïve HBeAg negative and HBeAg positive patients, and considered the unadjusted comparison
of the tenofovir treatment arms from trials 0102 in HBeAg negative patients and 0103
in HBeAg positive patients without use of a common reference, to represent insufficient
evidence. The PBAC considered that HBeAg positive CHB and HBeAg negative CHB are well
established as being distinct disease entities and that HBeAg status is both an effect
modifier and an independent predictor of outcome. Further, a comparison of outcomes
between HBeAg positive patients from one study and HBeAg negative patients from another
study is subject to considerable confounding with important differences between the
baseline characteristics of the patients in the trials, in addition to HBeAg status,
that may influence the outcome. The PBAC did not accept the claim that the lack of
a statistically significant difference between HBeAg positive and HBeAg negative subgroups
from the different trials for the primary outcome is evidence that the treatment is
equally effective in the two groups. The Committee hence rejected the application
for listing of tenofovir in HBeAg negative nucleoside naïve CHB patients, considering
insufficient evidence had been presented to support the claim of non-inferiority to
entecavir 0.5 mg.
In nucleoside treatment experienced patients the PBAC again considered the methods
used in the submission for the direct comparison of tenofovir to adefovir, in which
the results of the subgroups of nucleoside experienced patients from a trial in HBeAg
positive CHB patients and a trial in HBeAg negative CHB patients were combined, to
be flawed. The Committee also noted that non-inferiority margins were not pre-specified
for the subgroup analysis, and that using the non-inferiority margins specified in
the original studies, the subgroup analysis does not support the claim that tenofovir
is non-inferior to adefovir in treatment-experienced patients. The Committee hence
rejected the application for listing of tenofovir for the treatment of CHB in nucleoside
experienced patients.
Recommendation
TENOFOVIR DISOPROXIL FUMARATE, tablet, 300 mg
Restriction:
Section 100 – Highly Specialised Drugs Program
Private hospital authority required
Treatment of HIV infection in patients with:
a. CD4 cell counts of less than 500 per cubic millimetre; or
b. Viral load of greater than 10,000 copies per mL.
Treatment, as sole PBS-subsidised therapy, in a patient with HBeAg-positive chronic
hepatitis B who is nucleoside analogue naive and satisfies all of the following criteria:
(1) Histological evidence of chronic hepatitis on liver biopsy (except in patients
with coagulation disorders considered severe enough to prevent liver biopsy);
(2)(a) Abnormal serum ALT levels in conjunction with documented chronic hepatitis
B infection; or
(b) Elevated HBV DNA levels in conjunction with documented chronic hepatitis B infection;
(3) Female patients of child-bearing age are not pregnant, not breast-feeding, and
are using an effective form of contraception.
Persons with Child's class B or C cirrhosis (ascites, variceal bleeding, encephalopathy,
albumin less than 30 g per L, bilirubin greater than 30 micromoles per L) should have
their treatment discussed with a transplant unit prior to initiating therapy.
Pack size: 30
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
The sponsor welcomes the recommendation by the PBAC for the PBS
listing of tenofovir for treatment naïve patients with HBeAg
positive chronic Hepatitis B. The sponsor is committed to continue
to work closely with the PBAC and will address areas of uncertainty
that remain in order to obtain a recommendation for HBeAg negative
and treatment experienced patients.
