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Disease Analysis: COVID-19 Treatment

  • ID: 5357343
  • Report
  • March 2021
  • Region: Global
  • 168 pages
  • Pharma Intelligence
Latest Key Takeaways
  • Veklury (remdesivir) is the first and only approved antiviral for the treatment of hospitalized COVID-19 patients in the US, and has been rapidly adopted as the global standard of care for moderate and severe patients since its initial US Emergency Use Authorization (EUA) in May 2020 (full approval occurred in October 2020). Veklury’s rapid commercial success ($2.8bn in sales in 2020) has been driven by positive results from the US National Institutes of Health (NIH)-sponsored ACTT-1 study, which showed the drug significantly reduced the duration of hospitalization compared to placebo in patients with moderate-severe COVID-19 pneumonia. While negative results from the World Health Organization’s (WHO’s) SOLIDARITY trial in October 2020 contradicted these initial findings, suggesting that Veklury does not significantly reduce the duration of hospitalization or the risk of mortality in hospitalized patients, and resulting in the WHO recommending against its use, demand nevertheless increased in Q4. Indeed, in January 2021, Gilead noted that 50-60% of hospitalized US patients were being treated with remdesivir versus ~30% in October 2020, likely due to a lack of alternative options, thus the publisher expects the brunt of the impact of the WHO’s negative recommendation will only be felt once alternative agents become available for hospitalized patients.
  • Veklury faces myriad threats from pipeline candidates, including antivirals, immunomodulatory agents, monoclonal antibodies, and hyperimmune globulin therapies. Oral antivirals pose a particular threat, given that their similar mode of action means they are likely to produce comparable results in ongoing trials (or superior results if optimized for greater potency against the SARS-CoV-2 RNA polymerase), and their administration route would be more convenient than Veklury’s IV formulation. Favipiravir is the nearest-term threat, with emergency approvals in India and Russia, and ongoing studies in the outpatient, hospital, and prophylaxis settings, though disappointing results from a study in hospitalized patients in Kuwait suggest favipiravir’s use will be limited to outpatients.
  • Dexamethasone is the only immunomodulatory agent currently approved via emergency pathways in Japan, the EU, and the UK for the treatment of severe and critical COVID-19 pneumonia patients, and is recommended in both WHO and US NIH treatment guidelines. Dexamethasone has the enviable status of being the only therapy shown to significantly reduce the risk of mortality in severe/critical patients, as Veklury failed to do so in the ACTT-1 study. Other key advantages that have aided its rapid adoption as part of the standard of care include its flexibility of administration (oral, intramuscular, or IV) and its widespread generic availability, which could act as a substantial barrier for other branded immunomodulatory therapies seeking to supplant it.
  • In a minority of cases, SARS-CoV-2 infection is believed to trigger an overly aggressive immune response in which excessive amounts of pro-inflammatory cytokines are produced (termed a “cytokine storm”), which can subsequently drive extensive lung injury, lower oxygen saturation, multi-organ failure, and death. There is therefore substantial pipeline interest in repurposing immunomodulatory agents approved for various autoimmune indications for the treatment of severe and critical cases of COVID-19. However, results for the IL-6R antagonist class have been largely negative, with the exception of the REMAP-CAP and RECOVERY studies, which suggest Actemra can provide a modest reduction in mortality in severe and critical COVID-19 patients, contradicting more negative results from Roche’s own COVACTA and REMDACTA studies. The difference in outcomes may be partially due to increased use of combination therapy with corticosteroids since the COVACTA study was conducted, as well as earlier intervention with Actemra in the REMAP-CAP study (administered within 24 hours of entering intensive care).
  • A range of other immunomodulatory therapies have generated positive preliminary data, but Olumiant (baricitinib) is the only therapy thus far to be granted EUA by the FDA for the treatment of hospitalized COVID-19 (when used in combination with remdesivir). However, Olumiant’s benefit on recovery times is marginal, with an average one-day improvement compared to remdesivir alone. Olumiant also significantly reduced the risk of progression to mechanical ventilation or death, but the success on this composite endpoint was primarily driven by the mechanical ventilation component rather than mortality, meaning there is still substantial room for pipeline therapies to show greater improvements.
  • Monoclonal antibodies targeting the SARS-CoV-2 spike protein have been shown to reduce the risk of hospitalization in outpatients with mild-moderate infections at high risk of disease progression, and are expected to generate blockbuster sales in this setting in the first six to nine months of 2021. Thereafter, anticipated declines in the number of new infections in at-risk populations because of the ongoing rollout of highly effective vaccines will severely restrict their commercial potential in developed markets. In addition, data from pivotal trials of a range of vaccines suggest that they are highly effective at preventing hospitalization, meaning that even if an at-risk individual did acquire infection after vaccination, the subsequent use of monoclonal antibodies is unlikely to provide any additional benefit.
  • Eli Lilly’s bamlanivimab ± etesevimab and Regeneron’s REGEN-COV are the most advanced antibody candidates, with both cocktails having gained EUA from the FDA for use in the outpatient setting and positive opinions from the CHMP. Key disadvantages of the class include their IV administration, which makes widespread use in outpatients other than those at particularly elevated risk of hospitalization unfeasible, and their relatively high production costs and limited manufacturing capacity. Data in the hospital setting have also been underwhelming, with Eli Lilly suspending a trial in hospitalized patients due to lack of benefit, and Regeneron limiting enrollment to patients not on high-flow oxygen or ventilation due to an unspecified safety concern and poor risk/benefit profile. Finally, the possible spread of the South African viral variant (B1.351) could severely affect the utility of antibodies, as Eli Lilly’s combination has been shown to be ineffective against B1.351 in preclinical studies, while the casirivimab component of REGEN-COV is also ineffective (imdevimab retains neutralizing activity), meaning follow-on antibody combinations may be required.
  • Convalescent plasma therapy is highly unlikely to confer any benefit in hospitalized patients following a string of negative readouts from randomized controlled trials (PLACID, REMAP-CAP, and RECOVERY), which showed that it provides no mortality benefit or reduced risk of progression to severe disease versus standard of care alone. While the FDA’s EUA for convalescent plasma therapy still allows use in hospitalized patients earlier on in the course of the disease, it seems likely that the EUA will be withdrawn altogether following the NIH’s decision in March 2021 to suspend a trial in mild-moderate hospitalized patients following a planned interim analysis which showed the therapy was unlikely to confer any benefit.
  • The commercial outlook for COVID-19 therapeutics is expected to decline progressively throughout 2021 due to the phased implementation of global vaccination programs, which should substantially reduce both outpatient and hospital COVID-19 cases. Indeed, several vaccines being developed by Moderna, Pfizer/BioNTech, AstraZeneca, Novavax, and Johnson & Johnson have shown 66-95% effectiveness against symptomatic COVID-19 illness, and are also highly effective against COVID-19 hospitalization, though the potential emergence of new SARS-CoV-2 variants which may impair the effectiveness of vaccines against mild/moderate infections could partially revitalize the prospects for therapeutics aimed at the outpatient setting.
  • The overall likelihood of approval of a Phase I antiviral asset is 12.9%, and the average probability a drug advances from Phase III is 68.5%. Antiviral assets, on average, take 8.4 years from Phase I to approval, slightly shorter than the average of 9.0 years for all infectious disease assets. However, in the case of COVID-19, development periods have been shortened substantially to as little as 6-9 months as repurposed agents have been rushed through clinical trials and granted rapid reviews by regulators.
  • Pivotal trial data for a huge range of repurposed drugs are expected in H1 2021, including from Olumiant’s COV-BARRIER study evaluating the drug as a monotherapy against standard of care, and favipiravir’s PRESECO study evaluating its ability to prevent progression to severe infection in outpatients with mild-moderate infections.
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OVERVIEW
  • Latest key takeaways
DISEASE BACKGROUND
  • Definition
  • Transmission
  • Symptoms
  • Diagnosis
  • Patient segmentation
  • Risk factors
TREATMENT
  • Therapies with full or conditional approvals (eg Emergency Use Authorization)
  • Summary of US National Institutes of Health treatment guidelines
EPIDEMIOLOGY
  • High-risk population prevalence methodology
  • High-risk group prevalent populations
  • High-risk group prevalent cases
  • Infection fatality rate
  • Hospitalization
  • Hospitalized patient characteristics
MARKETED THERAPEUTIC AGENTS

PIPELINE THERAPEUTICS

KEY REGULATORY EVENTS
  • Pandemic Perspectives: US FDA Wastes No Time In COVID-19 Emergency Use Authorization Reviews
  • Dostarlimab, Zynteglo & COVID-19 Combo Drugs In The Spotlight At EMA
  • COVID Therapeutics’ Progress (Or Lack Thereof) May Be Political Vulnerability For US FDA
  • COVID Antibody Products May Get To Use Viral Load As Surrogate For Mutant-Targeted Versions
  • Coronavirus Notebook: UK To Speed Up Trials Of New Drugs, Expands Use Of Tocilizumab
  • Veklury Gets EMA All-Clear Over Kidney Problems, But Faces New Safety Review For Bradycardia
  • US FDA Authorizes Lilly’s COVID-19 mAB Combo For Lower Doses Than Tested In Phase III
PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS
  • Merck & Co. Will Manufacture J&J Vaccine, Other COVID-19 Medicines Under BARDA Deal
  • Start-Up Scanwell Adds Another Collaboration, Targets Home COVID-19 Testing With BD
  • Genexine, KGBio Ink $1.1bn License Pact
  • Sensyne Partners With Excalibur To Improve Usability Of COVID-19 Tests
  • US Supply Of OTC COVID-19 Tests Gets Boost Through $231.8M Contract For Australian Firm
  • Lilly, Vir/GSK Team Up On COVID-19 Antibody Combination Regimen
  • Thermo Fisher Scientific To Acquire Mesa Biotech
  • AzurRx Licenses First Wave Bio’s Niclosamide Formulations
CLINICAL TRIAL LANDSCAPE
  • Sponsors by status
  • Sponsors by phase
  • Recent events
VEKLURY

FAVIPIRAVIR

OTHER ANTIVIRALS
  • Other antiviral therapies to watch (no clinical data available)
IMMUNOMODULATORS

DEXAMETHASONE

ACTEMRA

OLUMIANT
  • SNG001
LENZILUMAB

OTILIMAB

MK-7110

ZYESAMI

CERC-002

TRADIPITANT

LERONLIMAB

OTHER IMMUNOMODULATORY AGENTS
  • Other immunomodulatory therapies to watch (limited or no clinical data available)
PROXALUTAMIDE

MONOCLONAL ANTIBODIES
  • Other antibody therapies to watch (no clinical data available)
HYPERIMMUNE GLOBULINS

MARKET DYNAMICS

FUTURE TRENDS

RECENT EVENTS AND ANALYST OPINION
  • Actemra for COVID-19 Treatment (March 10, 2021)
  • ABX464 for COVID-19 Treatment (March 5, 2021)
  • VIR-7831 for COVID-19 Treatment (March 3, 2021)
  • CERC-002 for COVID-19 Treatment (March 2, 2021)
  • Otilimab for COVID-19 Treatment (February 25, 2021)
  • IMU-838 for COVID-19 Treatment (February 17, 2021)
  • Aviptadil for COVID-19 Treatment (February 10, 2021)
  • Multiple Drugs for COVID-19 Treatment (January 26, 2021)
  • Ultomiris for COVID-19 Treatment (January 13, 2021)
  • CERC-002 for COVID-19 Treatment (January 5, 2021)
  • Ryoncil for COVID-19 Treatment (December 17, 2020)
  • Jakafi for COVID-19 Treatment (December 14, 2020)
  • C21 for COVID-19 Treatment (December 8, 2020)
  • Lenzilumab for COVID-19 Treatment (November 6, 2020)
  • Actemra for COVID-19 Treatment (October 21, 2020)
  • Pegylated Interferon Lambda for COVID-19 Treatment (October 15, 2020)
  • Bamlanivimab for COVID-19 Treatment (October 7, 2020)
  • Xpovio for COVID-19 Treatment (October 6, 2020)
  • REGN-COV for COVID-19 Treatment (September 29, 2020)
  • Pegylated Interferon Lambda for COVID-19 Treatment (September 28, 2020)
  • CD24Fc for COVID-19 Treatment (September 24, 2020)
  • Favipiravir for COVID-19 Treatment (September 23, 2020)
  • Actemra for COVID-19 Treatment (September 17, 2020)
  • Bamlanivimab for COVID-19 Treatment (September 16, 2020)
  • Olumiant for COVID-19 Treatment (September 14, 2020)
  • Kevzara for COVID-19 Treatment (September 1, 2020)
  • Tradipitant for COVID-19 Treatment (August 18, 2020)
  • Vyrologix for COVID-19 Treatment (August 11, 2020)
  • Actemra for COVID-19 Treatment (July 28, 2020)
  • Favipiravir for COVID-19 Treatment (July 22, 2020)
  • SNG001 for COVID-19 Treatment (July 20, 2020)
  • Octagam for COVID-19 Treatment (July 15, 2020)
  • Veklury for COVID-19 Treatment (July 10, 2020)
  • Kevzara for COVID-19 Treatment (July 2, 2020)
  • Hydroxychloroquine (Sandoz/Novartis) for COVID-19 Treatment (June 19, 2020)
  • Actemra for COVID-19 Treatment (June 17, 2020)
  • Veklury for COVID-19 Treatment (June 1, 2020)
  • Auxora for COVID-19 Treatment (May 28, 2020)
  • Veklury for COVID-19 Treatment (April 29, 2020)
  • Kevzara for COVID-19 Treatment (April 27, 2020)
KEY UPCOMING EVENTS

UNMET NEEDS
  • Additional therapies capable of reducing time to recovery and/or mortality in hospitalized patients
  • Convenient therapies capable of preventing progression to severe disease in outpatients
BIBLIOGRAPHY

APPENDIX

LIST OF FIGURES
Figure 1: COVID-19 infection fatality rates, by age group
Figure 2: COVID-19 hospitalization rates, by age group
Figure 3: Overview of pipeline drugs for COVID-19 treatment in the US
Figure 4: Pipeline drugs for COVID-19 treatment, by company
Figure 5: Pipeline drugs for COVID-19 treatment, by drug type
Figure 6: Pipeline drugs for COVID-19 treatment, by classification
Figure 7: Probability of success in the antiviral pipeline
Figure 8: Clinical trials in COVID-19 treatment and prevention
Figure 9: Top 10 drugs for clinical trials in COVID-19 treatment and prevention
Figure 10: Top 10 companies for clinical trials in COVID-19 treatment and prevention
Figure 11: Trial locations in COVID-19 treatment and prevention
Figure 12: COVID-19 treatment and prevention trials status
Figure 13: COVID-19 treatment and prevention trials sponsors, by phase
Figure 14: Market dynamics in COVID-19 treatment
Figure 15: Future trends in COVID-19 treatment
Figure 16: Otilimab for COVID-19 Treatment (February 25, 2021): Phase IIa - OSCAR
Figure 17: IMU-838 for COVID-19 Treatment (February 17, 2021): Phase II - CALVID-1
Figure 18: Multiple Drugs for COVID-19 Treatment (January 26, 2021): Phase II/III - BLAZE-1 (w/Etesevimab, Mild to Moderate) / (w/Bamlanivimab)
Figure 19: CERC-002 for COVID-19 Treatment (January 5, 2021): Phase II - COVID-19 ARDS
Figure 20: Actemra for COVID-19 Treatment (October 21, 2020): Phase III - Non-Critically Ill (U.S.)
Figure 21: Pegylated Interferon Lambda for COVID-19 Treatment (October 15, 2020): Phase II - ILIAD (University of Toronto)
Figure 22: Bamlanivimab for COVID-19 Treatment (October 7, 2020): Phase II/III - BLAZE-1 (w/Etesevimab, Mild to Moderate)
Figure 23: Xpovio for COVID-19 Treatment (October 6, 2020): Phase II - XPORT-CoV-1001
Figure 24: Pegylated Interferon Lambda for COVID-19 Treatment (September 28, 2020): Phase II - COVID-Lambda
Figure 25: Favipiravir for COVID-19 Treatment (September 23, 2020): Phase III - Japan
Figure 26: Actemra for COVID-19 Treatment (September 17, 2020): Phase III - EMPACTA
Figure 27: Bamlanivimab for COVID-19 Treatment (September 16, 2020): Phase II/III - BLAZE-1 (w/Etesevimab, Mild to Moderate)
Figure 28: Olumiant for COVID-19 Treatment (September 14, 2020): Phase III - ACTT 2
Figure 29: Kevzara for COVID-19 Treatment (September 1, 2020): Phase II/III - EFC16844 (Outside US)
Figure 30: Tradipitant for COVID-19 Treatment (August 18, 2020): Phase III - ODYSSEY
Figure 31: Vyrologix for COVID-19 Treatment (August 11, 2020): Phase II - CD10_COVID-19
Figure 32: Actemra for COVID-19 Treatment (July 28, 2020): Phase III - COVACTA (Global)
Figure 33: Favipiravir for COVID-19 Treatment (July 22, 2020): Phase III - India
Figure 34: SNG001 for COVID-19 Treatment (July 20, 2020): Phase II - SG016
Figure 35: Octagam for COVID-19 Treatment (July 15, 2020): Phase II - Istanbul
Figure 36: Veklury for COVID-19 Treatment (July 10, 2020): Phase III - SIMPLE-1 (Severe)
Figure 37: Kevzara for COVID-19 Treatment (July 2, 2020): Phase II/III - 6R88-COV-2040
Figure 38: Actemra for COVID-19 Treatment (June 17, 2020): Phase II - Italy (Investigator Initiated)
Figure 39: Veklury for COVID-19 Treatment (June 1, 2020): Phase III - SIMPLE-2 (Moderate)
Figure 40: Veklury for COVID-19 Treatment (April 29, 2020): Phase III - ACTT (NIAID) / Phase III - SIMPLE-1 (Severe) (1 of 2)
Figure 41: Veklury for COVID-19 Treatment (April 29, 2020): Phase III - ACTT (NIAID) / Phase III - SIMPLE-1 (Severe) (2 of 2)
Figure 42: Kevzara for COVID-19 Treatment (April 27, 2020): Phase II/III - 6R88-COV-2040
Figure 43: Key upcoming events in COVID-19 treatment (1 of 3)
Figure 44: Key upcoming events in COVID-19 treatment (2 of 3)
Figure 45: Key upcoming events in COVID-19 treatment (3 of 3)

LIST OF TABLES
Table 1: Clinical status scores and interpretations
Table 2: Priority populations for COVID-19 vaccination, and prevalence sources
Table 3: Total prevalent population in each COVID-19 high-risk group, by global region, 2020
Table 4: Proportion of hospitalized COVID-19 cases, by patient characteristic
Table 5: Marketed therapeutic agents for COVID-19
Table 6: Pipeline therapeutic agents for COVID-19 in the US
Table 7: Actemra for COVID-19 Treatment (March 10, 2021)
Table 8: ABX464 for COVID-19 Treatment (March 5, 2021)
Table 9: VIR-7831 for COVID-19 Treatment (March 3, 2021)
Table 10: CERC-002 for COVID-19 Treatment (March 2, 2021)
Table 11: Otilimab for COVID-19 Treatment (February 25, 2021)
Table 12: IMU-838 for COVID-19 Treatment (February 17, 2021)
Table 13: Aviptadil for COVID-19 Treatment (February 10, 2021)
Table 14: Multiple Drugs for COVID-19 Treatment (January 26, 2021)
Table 15: Ultomiris for COVID-19 Treatment (January 13, 2021)
Table 16: CERC-002 for COVID-19 Treatment (January 5, 2021)
Table 17: Ryoncil for COVID-19 Treatment (December 17, 2020)
Table 18: Jakafi for COVID-19 Treatment (December 14, 2020)
Table 19: C21 for COVID-19 Treatment (December 8, 2020)
Table 20: Lenzilumab for COVID-19 Treatment (November 6, 2020)
Table 21: Actemra for COVID-19 Treatment (October 21, 2020)
Table 22: Pegylated Interferon Lambda for COVID-19 Treatment (October 15, 2020)
Table 23: Bamlanivimab for COVID-19 Treatment (October 7, 2020)
Table 24: Xpovio for COVID-19 Treatment (October 6, 2020)
Table 25: REGN-COV for COVID-19 Treatment (September 29, 2020)
Table 26: Pegylated Interferon Lambda for COVID-19 Treatment (September 28, 2020)
Table 27: CD24Fc for COVID-19 Treatment (September 24, 2020)
Table 28: Favipiravir for COVID-19 Treatment (September 23, 2020)
Table 29: Actemra for COVID-19 Treatment (September 17, 2020)
Table 30: Bamlanivimab for COVID-19 Treatment (September 16, 2020)
Table 31: Olumiant for COVID-19 Treatment (September 14, 2020)
Table 32: Kevzara for COVID-19 Treatment (September 1, 2020)
Table 33: Tradipitant for COVID-19 Treatment (August 18, 2020)
Table 34: Vyrologix for COVID-19 Treatment (August 11, 2020)
Table 35: Actemra for COVID-19 Treatment (July 28, 2020)
Table 36: Favipiravir for COVID-19 Treatment (July 22, 2020)
Table 37: SNG001 for COVID-19 Treatment (July 20, 2020)
Table 38: Octagam for COVID-19 Treatment (July 15, 2020)
Table 39: Veklury for COVID-19 Treatment (July 10, 2020)
Table 40: Kevzara for COVID-19 Treatment (July 2, 2020)
Table 41: Hydroxychloroquine (Sandoz/Novartis) for COVID-19 Treatment (June 19, 2020)
Table 42: Actemra for COVID-19 Treatment (June 17, 2020)
Table 43: Veklury for COVID-19 Treatment (June 1, 2020)
Table 44: Auxora for COVID-19 Treatment (May 28, 2020)
Table 45: Veklury for COVID-19 Treatment (April 29, 2020)
Table 46: Kevzara for COVID-19 Treatment (April 27, 2020)
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