Overview
HIV, or the human immunodeficiency virus, is a lentivirus belonging to the Retroviridae family. HIV infects and destroys cells of the immune system, including cluster of differentiation 4+ (CD4+) T cells, macrophages, and dendritic cells, progressively impairing the infected individual’s ability to respond to subsequent infections. If left untreated for several years, the continued destruction of CD4+ T cells can lead to the development of acquired immunodeficiency syndrome (AIDS) (defined as a CD4+ T-cell count <200 cells/mm3), which is characterized by increased susceptibility to opportunistic infections and cancers. Although HIV infection is currently incurable, there are several effective highly active antiretroviral therapies (HAARTs) available that can suppress viral replication and prevent the progression of infection to AIDS.
Latest key takeaways
- The HIV treatment market in the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK) is expected to continue to expand through to 2025, driven primarily by increases in disease prevalence and continued uptake of Gilead’s Biktarvy and ViiV Healthcare’s portfolio of two-drug regimens. Uptake of new premium-priced therapies (Rukobia and lenacapavir) in heavily treatment-experienced (HTE) individuals will also drive growth, though their impact will be limited by the relatively low number of patients in the salvage setting. However, a plethora of products undergoing patent expiry across the forecast period will tip the market into decline from 2026, particularly Descovy, which is the preferred nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone, as physicians and payers will be provided with the ability to construct lower-cost once-daily regimens with generic Descovy and a generic third antiretroviral agent (such as dolutegravir, which will lose exclusivity in the US in 2027).
- Integrase strand transfer inhibitor (INSTI)-based regimens have become the top drug class due to their excellent efficacy and tolerability profiles as well as their very high barriers to resistance. Both US and EU guidelines now favor INSTI-based regimens as initial “recommended” regimens, which has driven a steady decline in the market share of protease inhibitor (PI)- and non-nucleoside reverse transcriptase (NNRTI)-based regimens in the first-line setting in recent years. PIs suffer from the requirement for co-administration with a pharmacokinetic boosting agent, which increases the risk of drug-drug interactions and adverse events, while NNRTIs suffer from low barriers to resistance. In the maintenance setting, the recent launches of Juluca, Dovato, and Cabenuva will further drive consolidation to INSTI-based regimens by offering patients the opportunity to simplify their treatment regimens from three drugs to two.
- Gilead’s flagship single-tablet regimen (STR) Biktarvy will continue to experience strong growth through to at least 2025. Biktarvy outpaced rival STRs to gain market-leader status in 2020, with sales amounting to $7.3bn. Further success in the HIV market will primarily be driven by patients switching over from Gilead’s older STRs (Genvoya, Stribild, Atripla, Complera, and Odefsey), its continued uptake in treatment-naïve patients, increasing HIV prevalence, and price rises in the US. While Biktarvy has suppressed its main rival Triumeq, the drug will face competition from other assets in ViiV Healthcare’s portfolio, most notably two-drug regimens Dovato, Juluca, and Cabenuva. Additional competition will come in 2025 following the launch of low-cost generics for Descovy, which makes up the NRTI backbone of Biktarvy. Coupling generic Descovy with an INSTI such as Tivicay will allow physicians to make their own less expensive three-drug regimens.
- ViiV Healthcare has maintained its second-place position in the HIV treatment market and is likely to grow its revenues due to new INSTI-based drug launches. Despite a continued decline for the company’s flagship three-drug regimen Triumeq, a shift in focus to the recently launched two-drug regimens Cabenuva, Dovato, and Juluca will be key in growing ViiV Healthcare’s revenues. The two-drug regimens have the advantage of potentially improved long-term tolerability and safety (although this is unproven), as well as a lower cost, giving them a competitive advantage. While initial uptake was muted due to physician concerns over resistance generation, long-term data demonstrating that resistance generation is minimal should allay these concerns. Both Dovato and Juluca have seen strong year-on-year growth, despite delays in patient switching due to the COVID-19 pandemic. Cabenuva has the advantage of a two-monthly injectable dosing schedule (recently extended from monthly); however, it is expected to gain only a minority of market share because it must be administered as two separate intramuscular injections by a physician, which will be a deterrent to some patients as well as posing a logistical challenge for primary care physicians by increasing the number of patient visits required.
- Remaining unmet needs in the HIV space include longer-acting drugs, simplified dosing regimens, and more treatment options for HTE patients. Initially, ViiV Healthcare’s two-drug regimens had a muted uptake due to a hypothetical lower barrier to resistance; however, uptake is now accelerating. Cabenuva, which has a two-monthly dosing regimen, has the benefit of being the first-to-market long-acting injectable (LAI); however, Gilead’s pipeline asset lenacapavir, which has a more attractive six-monthly dosing schedule, is likely to be a major challenger. Assuming a positive response from the FDA, lenacapavir could gain approval as early as February 2022 to become the second marketed LAI. Moreover, a partnership between Gilead and Merck & Co to develop a dual-combination therapy of islatravir/lenacapavir as a long-acting oral (LAO) and LAI is another major threat; however, this partnership is materially at risk owing to safety concerns surrounding islatravir (low lymphocyte and T-cell counts).
- With a minority of treatment-experienced patients generating resistance to multiple drug classes, there is a major unmet need for new mechanisms of action. There are three new drugs in late-phase development for the treatment of HTE patients, namely lenacapavir (capsid inhibitor), islatravir/doravirine (reverse transcriptase translocation inhibitor), and Vyrologix (CCR5 inhibitor).
- With Isentress being downgraded in US treatment guidelines, Merck & Co’s success in the HIV space largely rests on islatravir, a novel nucleoside reverse transcriptase translocation inhibitor, which has been selected to be the backbone drug for the company’s next generation of combination therapies. In November 2021, the FDA decided to place a clinical hold on trials of islatravir based on observations of a dose-dependent decline in levels of lymphocytes and CD4+ T-cells. The depletion of lymphocytes and T-cells is the opposite of the desired effect of a HIV treatment, and therefore Datamonitor Healthcare believes that this represents a potentially insurmountable safety hurdle for islatravir to overcome. Our base-case scenario is that development will continue once protocols have been amended to monitor lymphocytes and CD4+ T-cells, however, it is hard to imagine that there will be much interest for a HIV drug that requires routine monitoring and is associated with T-cell toxicity.
CONTENTS
7 OVERVIEW
7 Latest key takeaways
9 DISEASE BACKGROUND
9 Definition
9 Transmission
9 Symptoms
10 Diagnosis
12 TREATMENT
12 Nucleos(t)ide reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors
12 Integrase strand transfer inhibitors
12 Protease inhibitors
12 GP120 inhibitors
12 Guidelines
14 EPIDEMIOLOGY
14 Global epidemiology of HIV
15 MARKETED DRUGS
24 PIPELINE DRUGS
33 KEY REGULATORY EVENTS
33 CytoDyn Attempts To Return From RTF Letter, Files Expanded Access Request For Leronlimab
33 Theratechnologies Bids For Faster Trogarzo Administration
33 ViiV & Janssen Win English Funding First For HIV Therapy
34 Gilead’s Long-Acting HIV Drug Among Latest EU Filings
34 Could Lenacapavir Become First BTD in HIV To Reach Approval?
34 ViiV Seeks Label Expansion For Cabenuva
35 ViiV Anticipates 10%–15% Switchover To Long-Term HIV Option Cabenuva
36 PROBABILITY OF SUCCESS
37 LICENSING AND ASSET ACQUISITION DEALS
37 MPP Strikes Deal For Long-Acting Injectable HIV Candidate
37 Evotec And CAPRISA Team To Develop Broadly Neutralizing Antibody Against HIV
37 ViiV Looks Ahead With Third-Gen Integrase Inhibitor From Shionogi
37 Biocon Biologics And Serum Institute Join Forces
38 ViiV Aims To Extend HIV Drug Durations With Halozyme’s Technology
38 Patent Pool Partners With Mylan And Hetero On Dolutegravir
38 Merck & Co/Gilead Team To Take On ViiV In Long-Term HIV Treatment
39 Gritstone, Gilead Partner To Develop Therapeutic HIV Vaccine
40 CLINICAL TRIAL LANDSCAPE
41 Sponsors by status
42 Sponsors by phase
43 Recent events
46 DRUG ASSESSMENT MODEL
46 INSTI-based therapies
49 Long-acting INSTI-based therapies
50 NRTI-based therapies
51 Protease inhibitor-based therapies
51 NNRTI-based therapies
53 GP120-directed attachment inhibitor
53 Pipeline therapies
57 MARKET DYNAMICS
58 FUTURE TRENDS
58 Initial growth of the market through to 2025 will be offset by generic erosion of major brands
58 INSTIs will increasingly dominate the treatment paradigm, aided by additional drug launches
58 Biktarvy will retain its mantle as the highest-selling HIV therapy
59 ViiV Healthcare’s revenues will grow due to continued uptake of its simplified two-drug regimens
59 New salvage therapies will contribute to market growth, with lenacapavir expected to dominate in the longer term
60 CONSENSUS FORECASTS
65 RECENT EVENTS AND ANALYST OPINION
65 Multiple Drugs for HIV/AIDS (November 18, 2021)
66 MK-8591A for HIV/AIDS (October 25, 2021)
67 Dovato for HIV/AIDS (July 17, 2021)
68 Lenacapavir for HIV/AIDS (July 17, 2021)
69 Lenacapavir for HIV/AIDS (July 17, 2021)
71 Lenacapavir for HIV/AIDS (November 18, 2020)
73 KEY UPCOMING EVENTS
74 UNMET NEEDS
74 Longer-acting and simplified dosing regimens
74 Better treatment options for patients who fail multiple lines of therapy
75 BIBLIOGRAPHY
76 APPENDIX
LIST OF FIGURES
13 Figure 1: US and European treatment guidelines for HIV
24 Figure 2: Overview of pipeline drugs for HIV/AIDS treatment in the US
24 Figure 3: Pipeline drugs for HIV/AIDS treatment, by company
25 Figure 4: Pipeline drugs for HIV/AIDS treatment, by drug type
25 Figure 5: Pipeline drugs for HIV/AIDS treatment, by classification
36 Figure 6: Probability of success in the HIV/AIDS treatment pipeline
40 Figure 7: Clinical trials in HIV
40 Figure 8: Top 10 drugs for clinical trials in HIV
41 Figure 9: Top 10 companies for clinical trials in HIV
41 Figure 10: Trial locations in HIV
42 Figure 11: HIV trials status
43 Figure 12: HIV trials sponsors, by phase
46 Figure 13: Datamonitor Healthcare’s drug assessment summary for HIV treatment
57 Figure 14: Market dynamics in HIV treatment (one of two)
57 Figure 15: Market dynamics in HIV treatment (two of two)
58 Figure 16: Future trends in HIV treatment
67 Figure 17: MK-8591A for HIV/AIDS (October 25, 2021): Phase III – ILLUMINATE SWITCH A (8591A-017), Phase III – ILLUMINATE SWITCH B (8591A-018)
72 Figure 18: Lenacapavir for HIV/AIDS (November 18, 2020): Phase II/III – CAPELLA (HTE)
73 Figure 19: Key upcoming events in HIV/AIDS
LIST OF TABLES
16 Table 1: Marketed drugs for HIV/AIDS treatment
26 Table 2: Pipeline drugs for HIV/AIDS treatment in the US
61 Table 3: Historical global sales, by drug ($m), 2016–20
63 Table 4: Forecasted global sales, by drug ($m), 2022–26
65 Table 5: Multiple Drugs for HIV/AIDS (November 18, 2021)
66 Table 6: MK-8591A for HIV/AIDS (October 25, 2021)
68 Table 7: Dovato for HIV/AIDS (July 17, 2021)
69 Table 8: Lenacapavir for HIV/AIDS (July 17, 2021)
70 Table 9: Lenacapavir for HIV/AIDS (July 17, 2021)
71 Table 10: Lenacapavir for HIV/AIDS (November 18, 2020)