Patient Forecasts for Pipeline ARVs: Adults

Patient Forecasts for Pipeline ARVs: Adults Presented at: WHO/UNAIDS Annual Meeting with ARV Manufacturers and Stakeholders March 19-20, 2015 Vineet Prabhu Market Intelligence Team, CHAI HIV Access Program

2 Agenda General approach Variables considered Uptake curves Justifying uptake curve choice High level assumptions in approach Patient forecasts with product specific assumptions

General Approach: Start with Projected Patient Numbers with Status Quo; Layer In Uptake of New Products as They Become Available 1) Baseline forecast for competitive set assuming status quo* Total Pts = X Current Drug 2015 2020 2025 2) Forecast with first pipeline product Total Pts = X New Drug 1 Current Drug 2015 2020 2025 3) Forecast with second pipeline product Total Pts = X 2015 2020 2025 New Drug 2 New Drug 1 Current Drug Separate aggressive/moderate/conservative uptake against (i.e. taking from patients who would have otherwise been on) previously introduced drug(s) For each competitive pair, separate uptake curve amongst new vs. existing pts *Note: CHAI typically does 5-year forecasts, the latest ending 2018. 2019-2025 baseline patient numbers were extrapolated by using moving 3 year avg. growth rates to calculate total patients on ART and then assuming projected 2018 drug splits would hold 3

4 3 Primary Variables to Consider Anticipated price differential Financial incentive for MoHs to encourage uptake and change procurement decisions Relative clinical improvement Question of only initiating new patients vs. also actively switching existing patients Anticipated Launch Year Likely first availability of SRAapproved new product in LMICs with WHO guideline inclusion (equivalent FDC as incumbent) Taken together with an uptake curve, we can estimate total number of patients on each product in any given year

3 Possible Uptake Curves Considered for Each Competitive Pair; 2 Based on Historical Analogs % of Baseline Patients Switched to New Drug 5 Uptake Curves 100% 80% Aggressive switch scenario (hypothetical) 60% Moderate switch scenario: Historical TDF share (all ART pts) 40% 20% Conservative switch scenario: Historical ATV/r share (2L pts) 0% Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10

% of Baseline Patients Switched to New Drug 6 Scoring System to Justify Uptake Curve Choice a) Anticipated price relative to incumbent + 0-25% less 100% ++ 25-50% less +++ >50% less 80% Aggressive switch scenario (hypothetical) b) Clinical improvement relative to incumbent + Slightly better AE profile 60% 40% 20% 0% Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10 Moderate switch scenario: Historical TDF share (all ART pts) ++ Significantly better AE profile OR greater viral suppression/less resistance +++ Significantly better AE profile AND greater viral suppression/less resistance Also considered, but with lower importance: Conservative switch scenario: Historical ATV/r share (2L pts) c) Substitutability major clinical/scientific reason to not switch patients? + Different class of drug (e.g. DTG vs. EFV) ++ Same class of drug, but different end active ingredient (e.g. DRV vs. ATV) +++ Same end active ingredient (e.g. TAF vs. TDF)

7 High Level Assumptions to Avoid Pitfall of False Precision with Many Variables Involved For each new product, there is one primary patient segment per line of treatment (i.e. competitive set) worth forecasting use outside that represents further upside Clinical data for new products (in context of anticipated use) will be incumbents; expect rapid inclusion in WHO Guidelines released immediately post-sra approval Where SRA approved in even numbered year, WHO inclusion assumed to be next odd numbered year when updated guidelines are released Choice of uptake curve will reflect preferred/alternate status and timing of inclusion in local guidelines Rapid country-level registration and availability once SRA approval secured Negligible uptake of new products without introduction as FDCs that represent the same/lower pill burden as incumbent products for major regimens i.e. only launch year of equivalent FDC considered in forecast Relative price differentials between products will remain largely the same during the forecast period Any changes not substantial enough to warrant changing initial uptake curve choice VL testing will be assumed to not significantly change number of 2L patients overall as net effect of VL testing in the real world remains to be seen CHAI s baseline forecast based on this assumption

Four Competitive Sets are Most Apparently Relevant to Model for Adults in GA-LMICs 8 1 2 Replacing 1L TDF Replacing 1L EFV & NVP Established Product TDF TAF EFV 600mg and NVP EFV 400mg and DTG 3 4 Replacing 2L TDF & AZT Replacing 2L PIs TDF and AZT (+3TC/FTC) DTG LPV/r and ATV/r DRV/r

Four Competitive Sets are Most Apparently Relevant to Model for Adults in GA-LMICs 9 1 Replacing 1L TDF 2 Replacing 1L EFV & NVP Established Product TDF TAF EFV 600mg and NVP EFV 400mg and DTG 3 4 Replacing 2L TDF & AZT Replacing 2L PIs TDF and AZT (+3TC/FTC) DTG LPV/r and ATV/r DRV/r

KEY Adult 1L Backbone Replacing TDF LMIC Launch Year (of equivalent FDC) TAF 2019 (2018 SRA approval) vs. TDF or TDF(xb) Price Differential +++ Clinical Improvement + Substitutability +++ Uptake curve choice: new patients Uptake curve choice: existing patients Aggressive Aggressive Price relative to incumbent + 0-25% less ++ 25-50% less +++ >50% less Clinical Improvement relative to incumbent + Slightly better AE profile ++ Significantly better AE profile OR greater viral suppression/less resistance +++ Significantly better AE profile AND greater viral suppression/less resistance Substitutability + Different class of drug ++ Same class of drug, but different end active ingredient +++ Same end active ingredient 10

TAF Expected to Rapidly Account for Vast Majority of First Line Tenofovir Patients Number of Patients (Millions) Patient Forecast for Replacement of 1L TDF, 2015-2025 16 14 12 11.4 12.1 12.5 12.8 13.1 13.4 13.6 13.8 14.0 10 8 7.2 8.8 10.2 3.1 5.1 9.2 10.7 12.3 13.1 13.3 6 4 2 0 5.6 5.6 7.2 8.8 10.2 11.4 12.1 9.4 7.7 3.9 2.7 1.4 0.7 0.7 TAF TDF Note: For each year, sum of all segments in bar chart reflects projected patient totals for current drug(s) shown for pertinent setting in the absence of newer drugs being introduced 11

% of Total Patients TAF Expected to Rapidly Account for Vast Majority of First Line Tenofovir Patients Patient Forecast for Replacement of 1L TDF, 2015-2025 100% 5.6 7.2 8.8 10.2 11.4 12.1 12.5 12.8 13.1 13.4 13.6 13.8 14.0 Total Patients (millions) 80% 25% 40% 60% 100% 100% 100% 100% 100% 100% 70% 80% 90% 95% 95% 40% 75% 60% 20% 0% 30% 20% 10% 5% 5% TAF TDF Note: For each year, sum of all segments in bar chart reflects projected patient totals for current drug(s) shown for pertinent setting in the absence of newer drugs being introduced 12

13 Other Considerations for 1L TAF Forecast Timing of TAF launch in LMICs (i.e. generic SRA approval, inclusion in WHO guidelines) highly dependent on availability and acceptability of clinical data from cobicistat-unboosted studies Current TAF/FTC switching study in virologically suppressed rather than treatment naïve patients Uptake shown assumes licensing agreements that allow combination with all agents, including DTG Dose-reduced TDF (TDF(xb)) has potential to provide cost savings bridge to eventual availability of TAF Clinical data yet to be developed

Four Competitive Sets are Most Apparently Relevant to Model for Adults in GA-LMICs 14 1 Replacing 1L TDF 2 Replacing 1L EFV & NVP Established Product TDF TAF EFV 600mg and NVP EFV 400mg and DTG 3 4 Replacing 2L TDF & AZT Replacing 2L PIs TDF and AZT (+3TC/FTC) LPV/r and ATV/r DTG DRV/r

KEY Adult 1L Replacing EFV 600 and NVP LMIC Launch Year (of equivalent FDC) EFV 400mg DTG 2017 (2017 SRA approval) 2017 (2017 SRA approval) vs. EFV 600 vs. NVP* vs. EFV 600 vs. NVP* vs. EFV 400** Price Differential + + +++ ++ ++ Clinical Improvement + ++ +++ +++ ++ Substitutability +++ ++ + + + Uptake curve choice: new patients Uptake curve choice: existing patients Moderate Moderate Aggressive Aggressive Moderate Moderate Conservative Moderate Moderate Moderate *NVP pts. who would not have otherwise been switched to EFV 600mg **Incl. pts who would have otherwise been on EFV 600mg Price relative to incumbent + 0-25% less ++ 25-50% less +++ >50% less Clinical Improvement relative to incumbent + Slightly better AE profile ++ Significantly better AE profile OR greater viral suppression/less resistance +++ Significantly better AE profile AND greater viral suppression/less resistance Substitutability + Different class of drug ++ Same class of drug, but different end active ingredient +++ Same end active ingredient 15

Number of Patients (Millions) DTG Likely to Represent Majority of Patients in 1L Who Would Have Otherwise Been on NNRTIs Patient Forecast for Replacement of 1L NNRTIs, 2015-2025 20 18 16 14 12 10 8 6 4 2 0 9.9 4.8 5.1 11.5 4.9 6.6 13.1 5.0 8.1 14.7 5.1 9.5 15.9 2.0 3.5 1.0 4.5 8.4 16.6 17.1 17.5 1.9 3.9 7.3 6.1 2.8 3.1 5.0 8.5 3.4 2.4 3.2 17.9 18.3 18.6 18.9 19.1 10.6 11.8 12.7 13.2 13.7 3.5 3.5 3.5 3.5 3.5 1.8 1.4 1.2 1.0 0.9 2.0 1.5 1.3 1.1 1.0 DTG EFV 400mg NVP EFV 600mg Note: For each year, sum of all segments in bar chart reflects projected patients totals across current drugs for pertinent setting in the absence of newer drugs being introduced 16

% of Total Patients DTG Likely to Represent Majority of Patients in 1L Who Would Have Otherwise Been on NNRTIs Patient Forecast for Replacement of 1L NNRTIs, 2015-2025 100% 80% 60% 40% 20% 0% 9.9 11.5 13.1 14.7 15.9 16.6 17.1 17.5 17.9 18.3 18.6 18.9 19.1 Total Patients 12% (millions) 21% 49% 6% 38% 35% 36% 43% 49% 11% 59% 28% 65% 68% 70% 72% 51% 57% 62% 65% 53% 24% 44% 17% 18% 29% 19% 14% 18% 19% 19% 10% 19% 19% 19% 11% 8% 6% 5% 5% 8% 7% 6% 5% DTG EFV 400mg NVP EFV 600mg Note: For each year, sum of all segments in bar chart reflects projected patient totals for current drug(s) shown for pertinent setting in the absence of newer drugs being introduced 17

18 Caveats to 1L DTG & EFV 400mg Forecast Timing of DTG launch in LMICs (i.e. generic SRA approval, inclusion in WHO guidelines) highly dependent on availability and acceptability of clinical data from studies with tenofovir Limited H2H data of TLE vs. TLD Uptake shown assumes licensing agreements that allow combination with all current and future 1L backbone agents, including TAF Possibility that EFV 400mg could be perceived as a developing worldonly or inferior product, reducing MoH receptivity

Four Competitive Sets are Most Apparently Relevant to Model for Adults in GA-LMICs 19 1 Replacing 1L TDF 2 Replacing 1L EFV & NVP Established Product TDF TAF EFV 600mg and NVP EFV 400mg and DTG 3 Replacing 2L TDF & AZT 4 Replacing 2L PIs TDF and AZT (+3TC/FTC) LPV/r and ATV/r DTG DRV/r

Adult 2L Replacing TDF and AZT (+3TC/FTC) in Combination with PIs KEY LMIC Launch Year (of equivalent FDC) DTG 2017 (2016 SRA approval) (single would be equivalent to dual NRTI in this setting) vs. TDF vs. AZT Price Differential +++ +++ Clinical Improvement ++ +++ Substitutability + + Uptake curve choice: new patients Uptake curve choice: existing patients Aggressive Moderate Aggressive Aggressive Price relative to incumbent + 0-25% less ++ 25-50% less +++ >50% less Clinical Improvement relative to incumbent + Slightly better AE profile ++ Significantly better AE profile OR greater viral suppression/less resistance +++ Significantly better AE profile AND greater viral suppression/less resistance Substitutability + Different class of drug ++ Same class of drug, but different end active ingredient +++ Same end active ingredient 20

Number of Patients (Thousands) DTG Will Likely Replace all 2L TDF & AZT use by 2025 Patient Forecast for Replacement of 2L TDF & AZT, 2015-2025 1,000 865 891 913 934 954 972 985 996 800 773 675 149 282 600 400 200 0 347 263 323 185 306 114 283 300 315 328 301 277 397 485 578 507 158 226 623 108 182 734 801 828 847 862 55 28 29 29 29 144 125 115 109 105 DTG AZT TDF Note: For each year, sum of all segments in bar chart reflects projected patient totals for current drug(s) shown for pertinent setting in the absence of newer drugs being introduced 21

% of Total Patients DTG Will Likely Replace all 2L TDF & AZT use by 2025 Patient Forecast for Replacement of 2L TDF & AZT, 2015-2025 100% 397 485 578 675 773 865 891 913 934 954 972 985 996 Total Patients (thousands) 80% 60% 29% 38% 46% 51% 19% 42% 33% 57% 68% 79% 84% 85% 86% 87% 35% 40% 20% 0% 71% 62% 54% 49% 39% 32% 18% 25% 12% 20% 6% 3% 3% 3% 3% 15% 13% 12% 11% 11% DTG AZT TDF Note: For each year, sum of all segments in bar chart reflects projected patient totals for current drug(s) shown for pertinent setting in the absence of newer drugs being introduced 22

23 Other Considerations for 2L DTG Forecast Possibility of DTG being included as an alternative option in 2015 guidelines, leading to some use in LMICs prior to 2017 Even faster uptake of DTG in 2L possible if FDCs with PIs (one-pill, once-aday) become available, further reducing pill burden relative to today s 2L regimens (2 pill minimum)

Four Competitive Sets are Most Apparently Relevant to Model for Adults in GA-LMICs 24 1 Replacing 1L TDF 2 Replacing 1L EFV & NVP Established Product TDF TAF EFV 600mg and NVP EFV 400mg and DTG 3 Replacing 2L TDF & AZT 4 Replacing 2L PIs TDF and AZT (+3TC/FTC) LPV/r and ATV/r DTG DRV/r

KEY Adult 2L Replacing ATV/r and LPV/r LMIC Launch Year (of equivalent FDC) DRV/r 2016 (2015 guideline inclusion) vs. LPV/r vs. ATV/r Price Differential + + Clinical Improvement +++ ++ Substitutability ++ ++ Uptake curve choice: new pts Uptake curve choice: existing pts Aggressive Moderate Moderate Conservative Price relative to incumbent + 0-25% less ++ 25-50% less +++ >50% less Clinical Improvement relative to incumbent + Slightly better AE profile ++ Significantly better AE profile OR greater viral suppression/less resistance +++ Significantly better AE profile AND greater viral suppression/less resistance Substitutability + Different class of drug ++ Same class of drug, but different end active ingredient +++ Same end active ingredient 25

Number of Patients (Thousands) DRV/r Could Represent Majority of 2L PI Patients by 2025 Patient Forecast for Replacement of 2L PIs, 2015-2025 1,000 858 884 906 926 947 964 977 988 800 768 672 124 227 300 382 459 518 560 600 628 600 577 63 400 408 39 489 96 163 222 288 340 347 336 305 279 261 240 226 DRV/r ATV/r 200 369 393 414 387 356 292 236 188 163 150 143 138 134 LPV/r 0 Note: For each year, sum of all segments in bar chart reflects projected patient totals for current drug(s) shown for pertinent setting in the absence of newer drugs being introduced 26

% of Total Patients DRV/r Could Represent Majority of 2L PI Patients by 2025 Patient Forecast for Replacement of 2L PIs, 2015-2025 100% 80% 60% 408 489 557 672 768 858 884 906 926 947 964 977 988 Total Patients 10% 9% (thousands) 20% 16% 28% 26% 34% 42% 33% 50% 55% 58% 61% 64% 37% 40% 40% 20% 90% 80% 72% 58% 46% 34% 39% 27% 37% 21% 33% 29% 27% 25% 23% 18% 16% 15% 14% 14% DRV/r ATV/r LPV/r 0% Note: For each year, sum of all segments in bar chart reflects projected patient totals for current drug(s) shown for pertinent setting in the absence of newer drugs being introduced 27

28 Other Considerations for DRV/r Forecast Uptake of DRV/r highly dependent on presumed price reductions to parity with ATV/r, at current clinical dosing Process chemistry improvements and labor cost reductions Timing of use in LMICs assumes promotion to preferred/alternate in 2015 WHO guidelines, regardless of availability of heat-stable FDC at the time Presumed generic FDC availability by mid-2016 Even faster uptake of DRV/r possible if: a) Dose-reduction efforts pan out, further reducing the price b) FDCs with DTG and TDF/3TC and/or TDF/FTC become available, further reducing pill burden relative to incumbent 2 nd -line regimens (2 pill minimum)

29 Conclusions Fast/first movers will benefit from the opportunity presented by these products as current drugs are replaced by cheaper and more efficacious products Manufacturers encouraged to position themselves favorably by securing timely SRA approvals and country registrations, and preparing production capacity as necessary Several products identified with clinical and price benefits; however rate of uptake will be highly dependent on timely inclusion in WHO guidelines