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
- HIV, or the human immunodeficiency virus, infects and destroys cells of the immune system, 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), 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. HIV represents a major global clinical and economic burden, with the World Health Organization (WHO) estimating that there were 38.4 million people living with HIV at the end of 2021, 1.5 million of whom were newly infected during that year. The majority of people (54%) living with HIV in 2021 were in East and Southern Africa, where the prevalence of infection is highest.
- 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. 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 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. This momentum continued in 2021, with sales amounting to $8.6bn. 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 more 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 edge. 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; 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 recently approved (in the EU) 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 US approval in December 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 significant proportion of treatment-experienced patients generating resistance to multiple drug classes, there is a major unmet need for new mechanisms of action. However, there is one drug combination remaining in late-phase development for the treatment of HTE patients, namely islatravir/doravirine (reverse transcriptase translocation 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. However, despite this safety hurdle, the development of islatravir has resumed, albeit at lower dosages. Our best case scenario is that efficacy will be maintained at lower dosages and no safety issues will be observed once protocols are amended to monitor lymphocytes and CD4+ T cells. However, there are concerns over the commercial potential of 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
34 KEY REGULATORY EVENTS
34 Gilead Gets Lenacapavir To EU Approval For HIV Salvage Therapy, Awaits FDA’s Call
34 CHMP Recommends Extension Of Indication For Genvoya
34 CHMP Recommends Gilead’s Sunlenca For Patients With Multi-Drug Resistant HIV
34 FDA Expands Use Of Approved HIV Therapies
35 FDA Issues CRL For Lenacapavir
35 CytoDyn Attempts To Return From RTF Letter, Files Expanded Access Request For Leronlimab
36 Theratechnologies Bids For Faster Trogarzo Administration
36 ViiV & Janssen Win English Funding First For HIV Therapy
37 PROBABILITY OF SUCCESS
38 LICENSING AND ASSET ACQUISITION DEALS
38 Genuine Biotech Ties Up With Shanghai Fosun For Azvudine
38 LinKinVax Signs Worldwide Licensing Agreement With Inserm Transfert
38 Biocon Finalizes Merger Between Covidshield And Biologics Business
38 MPP Strikes Deal For Long-Acting Injectable HIV Candidate
39 Evotec And CAPRISA Team To Develop Broadly Neutralizing Antibody Against HIV
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
52 NNRTI-based therapies
53 GP120-directed attachment inhibitor
54 Pipeline therapies
58 MARKET DYNAMICS
59 FUTURE TRENDS
59 Initial growth of the market through to 2025 will be offset by generic erosion of major brands
59 INSTIs will increasingly dominate the treatment paradigm, aided by additional drug launches
59 Biktarvy will retain its mantle as the highest-selling HIV therapy
60 ViiV Healthcare’s revenues will grow due to continued uptake of its simplified two-drug regimens
60 New salvage therapies will contribute to market growth, with lenacapavir expected to dominate in the longer term
61 CONSENSUS FORECASTS
66 RECENT EVENTS AND ANALYST OPINION
66 Lenacapavir for HIV / AIDS (March 1, 2022)
66 Multiple Drugs for HIV/AIDS (November 18, 2021)
67 MK-8591A for HIV/AIDS (October 25, 2021)
69 Dovato for HIV/AIDS (July 17, 2021)
70 Lenacapavir for HIV/AIDS (July 17, 2021)
71 Lenacapavir for HIV/AIDS (July 17, 2021)
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
37 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
58 Figure 14: Market dynamics in HIV treatment (one of two)
58 Figure 15: Market dynamics in HIV treatment (two of two)
59 Figure 16: Future trends in HIV treatment
69 Figure 17: MK-8591A for HIV/AIDS (October 25, 2021): Phase III – ILLUMINATE SWITCH A (8591A-017), Phase III – ILLUMINATE SWITCH B (8591A-018)
73 Figure 18: 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
62 Table 3: Historical global sales, by drug ($m), 2017–21
64 Table 4: Forecasted global sales, by drug ($m), 2022–26
66 Table 5: Lenacapavir for HIV / AIDS (March 1, 2022)
67 Table 6: Multiple Drugs for HIV/AIDS (November 18, 2021)
68 Table 7: MK-8591A for HIV/AIDS (October 25, 2021)
69 Table 8: Dovato for HIV/AIDS (July 17, 2021)
70 Table 9: Lenacapavir for HIV/AIDS (July 17, 2021)
71 Table 10: Lenacapavir for HIV/AIDS (July 17, 2021)