Health Care Archives - Page 3 of 5 - Visible Alpha

Visible Alpha Health Care

In our weekly round-up of the top charts and market-moving analyst insights: Novartis’ Entresto (NYSE: NVS) faces generic competition & Medicare price cuts in the U.S.; Salesforce (NYSE: CRM) mitigates its revenue slowdown with margin expansion; and Sleep Country Canada (TSX: ZZZ) expands its portfolio amid a growth slowdown.

Novartis’ Entresto Facing Generic Competition & Medicare Price Cuts in the U.S.

Novartis’ (NYSE: NVS) Entresto is one of 10 prescription drugs that initially fall under the Inflation Reduction Act (IRA) of 2022, which allows Medicare to negotiate lower prices directly with drug companies. Entresto is prescribed for patients with heart failure to help reduce the risk of death and hospitalization. The expected reduction in U.S. prices will take effect from 2026.

In the case of Entresto, however, generic competition is expected to be a greater threat than lowered pricing for U.S. revenue from 2025 onward. Analysts expect generic competition to begin taking effect between 2025 and 2027.

Novartis has thwarted attempts by generic makers of Entresto since 2019, utilizing patent infringement lawsuits. Notably, the company has settled with several generic companies regarding a U.S. launch date for Entresto generics. Novartis has guided investors to model 2025 as a reasonable timeline to assume generic competition. Even though one Entresto patent will expire in 2025 based on a recent court decision, other key Entresto patents could survive through 2027.

Novartis' Entresto Facing Generic Competition & Medicare Price Cuts in the U.S.

Salesforce to Mitigate Revenue Slowdown with Margin Expansion

Salesforce (NYSE: CRM) has seen its revenue growth slow down significantly over the last year as economic challenges prompted many companies to tighten their spending. Analysts expect the company’s total revenue to increase by 11% in 2024, a notable slowdown from its 18.3% growth in fiscal 2023 and the 24.7% surge in fiscal 2022.

According to Visible Alpha consensus, however, Salesforce’s margins are expected to continue to expand. Analysts expect the company to generate an operating margin (GAAP) of 13.5% in 2024, up from 3.3% in fiscal 2023, and 2.1% in fiscal 2022.

The growth in profitability is on the back of several measures the company has implemented over the past year. Salesforce laid off about 10% of its workforce in early 2023, halted all major acquisitions, and has also reined in its operating expenses. The company’s selling and marketing expenses, a major expense line for the company, are projected to decline by -5.2% in 2024, while total operating expenses are projected to fall by -2.8%.

Salesforce to Mitigate Revenue Slowdown with Margin Expansion

Sleep Country Canada Expands Portfolio Amid Growth Slowdown

Analysts expect Canadian specialty sleep retailer Sleep Country Canada (TSX: ZZZ) to see total growth improve starting in 2023, following a sharp decline in 2022, according to Visible Alpha consensus. The company has seen total growth slow down since last year due to reduced consumer spending on big-ticket discretionary items. Total growth combines the percentage increases in same-store sales and sales from new stores.

In an effort to enhance its portfolio, the omnichannel specialty sleep retailer has been on an acquisition spree since 2021. Earlier this year, the company acquired the Canadian operations of mattress retailer Casper Sleep, and late last year, it acquired the direct-to-consumer sleep brand Silk & Snow. Additionally, in 2021, Sleep Country Canada made investments in Hush Blankets and Sleepout, a start-up curtain company.

Novartis Drug to Face Generics and Price Cuts; Salesforce Expands Margins; Sleep Country Wakes Up With Acquisitions

After decades of research and development hiccups, therapeutic approaches that modify the course of Alzheimer’s disease (AD) are finally available to patients. The successful development of amyloid β targeting antibodies marks a major advancement for AD. Biogen (NASDAQ: BIIB) and Eisai (TSE: 4523) developed Leqembi (lecanemab), which was approved for early-stage AD by the FDA in July 2023. Eli Lilly (NYSE: LLY) recently reported positive Phase 3 data for its amyloid β targeting antibody, donanemab, also for early-stage AD. Donanemab is expected to be approved by the FDA by year end.

Both Leqembi and donanemab are novel disease-modifying antibody-based therapies that target the underlying cause of Alzheimer’s disease. According to Visible Alpha consensus, revenue projections for Leqembi substantially exceed projections for donanemab.

Commercial prospects for Leqembi versus donanemab for early AD

Both Leqembi and donanemab are approved for early-stage AD which includes patients with mild cognitive impairment or mild dementia. It is estimated that in the U.S. there are 6.7 million people living with Alzheimer’s dementia¹. Globally, the prevalence of AD-related dementia is about 55 million.² Early-stage AD accounts for approximately 31.5 million patients globally and about 6.1 million of those are addressable and positive for amyloid β³, thus potential candidates for Leqembi and donanemab.3,4 Analysts estimate 1 million to 2 million patients in the U.S. could qualify for amyloid β therapy.

Visible Alpha consensus revenue projections show Leqembi reaching peak unadjusted revenues of $9.9 billion in 2034 and donanemab reaching peak unadjusted revenues of $6.4 billion in 2032 (Figure 1). These reflect unadjusted revenues — not accounting for regulatory risk for Leqembi approval in the EU or the rest of the world, as Leqembi is currently approved only in the US. Donanemab is not yet approved in the U.S., EU or the rest of the world. Based on the Phase 3 data, analysts expect approval of both drugs globally. Leqembi’s superior market prospects are largely driven by a safer profile (discussed below) and the potential approval of a subcutaneous injection that would allow convenient at-home administration using an auto-injector. Potentially, donanemab could gain from targeting younger preclinical AD patients with milder disease.

While Biogen/Eisai have set the annual cost of Leqembi at $26K in the US, analysts’ consensus net annual price is capped at approximately $20.9K in 2030, after discounts and rebates. Donanemab is likely to be within range or less. It is likely that the cost for amyloid β PET scans and biomarker analysis could increase actual cost per patient.

Figure 1: Visible Alpha consensus revenue projections for Leqembi and donanemab for early Alzheimer’s disease. Analysts project a broader market penetration for Leqembi over donanemab, mainly driven by Leqembi’s better safety profile. Efficacy was generally similar between Leqembi and donanemab (see Table 1 and 2)

Novel Amyloid β Targeting Therapies Mark Major Advance in Treating Alzheimer’s Disease

Significance of targeting amyloid β plaques and tau proteins for AD

AD patients are in dire need of effective medicines that provide more than mere symptomatic relief. Before the recent advent of approaches targeting amyloid β plaques, available drugs treated cognitive symptoms (memory and thinking) by affecting chemical messages between neurons. These drugs temporarily improve symptoms but do not alter the underlying course of the disease, and they fall into two main categories – cholinesterase inhibitors and glutamate regulators. Examples include Aricept (Donepezil), Razadyne (Galantamine), Exelon (Rivastigmine), Namenda (Memantine) and Namzaric (Memantine + Donepezil).5

The development of antibodies targeting amyloid plaque formation marks a major advance in changing the course of the disease by targeting the underlying pathology. Biogen’s and Eisai’s Leqembi (lecanemab) is the first antibody approved (traditional or full approval) that targets amyloid β plaque formation in the treatment of AD. Previously, Leqembi was granted accelerated (conditional) approval in January 2023. Following in the footsteps of Leqembi is Eli Lilly’s donanemab, expected to be approved by the end of 2023. We discount Biogen’s Aduhelm which was granted accelerated approval in June 2021 under controversy and has since been withdrawn from the market.

Biology behind amyloid β plaque and tau protein in the pathology of AD

AD is characterized by amyloid plaque and neurofibrillary tangle formation in the brain. Amyloid β protein is the central component of extracellular amyloid plaques and is considered the major pathological driver of AD along with tau protein that make up the neurofibrillary tangles.6 Amyloid plaque accumulation directly results in synaptic dysfunction, neurodegeneration, and, ultimately, clinical symptoms.7 Drug development over the past decade or more has been directed at resolving amyloid β plaques. Notably, several earlier attempts at developing therapies targeting amyloid-beta plaques failed in clinical trials, casting doubt on the amyloid β plaques hypothesis in the development of AD.

Figure 2: Depiction of experimental model of amyloid β (Aβ) and tau protein synergy in propagating Alzheimer’s disease. Aβ plaques accelerate tau spreading and cognitive decline in Alzheimer’s disease (Busche & Hyman; Synergy between amyloid-β and tau in Alzheimer’s disease. Nature Neuroscience; 23, 1183–1193; 2020).

Depiction of experimental model of amyloid β (Aβ) and tau protein synergy in propagating Alzheimer’s disease. Aβ plaques accelerate tau spreading and cognitive decline in Alzheimer’s disease (Busche & Hyman; Synergy between amyloid-β and tau in Alzheimer’s disease. Nature Neuroscience; 23, 1183–1193; 2020).

Comparing Leqembi and donanemab

Target AD patient population: Leqembi and donanemab were both tested in early AD, i.e., patients with mild cognitive impairment/mild dementia8 . However, within the early-AD patient populations patients were further classified based on the extent of the amyloid plaque and/or tau protein that correlates with disease progression.

Regulatory status: The FDA approved Leqembi on January 6, 2023, under the accelerated approval pathway sought by Biogen and Eisai based on Phase 2 data. Following the completion of the Phase 3 confirmatory trial that verified the clinical benefit and safety, the FDA converted the accelerated approval to traditional full approval on July 6, 2023. Ely Lilly applied for accelerated approval for donanemab after Phase 2 studies, but the FDA rejected the accelerated application. Phase 3 donanemab studies have now been completed and we expect FDA approval of donanemab the end of 2023.

Targeting amyloid β plaque formation: Both Leqembi and donanemab are monoclonal antibodies targeting amyloid β plaques that develop in AD. Leqembi binds to soluble amyloid β protofibrils (prior to plaque formation), which are known to be more toxic to neurons than monomers or insoluble fibrils.9 On the other hand, donanemab binds to a truncated form of β-amyloid present only within formed amyloid plaques.8 The binding of donanemab to the truncated form of β-amyloid facilitates plaque clearance through microglial mediated phagocytosis.

Dosing: Both are administered by intravenous injection, but donanemab is administered every four weeks and Leqembi every two weeks. It is notable that an extension clinical trial is ongoing that is testing a subcutaneous injection auto-injector of Leqembi administered every week. If approved, it would allow patients to administer at home without the need to visit an infusion center. This ease of self-injection at home with an auto-injector is a meaningful advantage for Leqembi.

Efficacy data, patient populations, and endpoints: Phase 3 registration study data has been published in peer reviewed journals for both Leqembi and donanemab.8,9 Donanemab data was presented at the Alzheimer’s Association International Conference (AAIC) in Amsterdam on July 17, 2023. Though the two trials enrolled early-stage AD patients, there were differences in how the patient population were stratified based on AD progression as measured by brain protein tau, a predictive biomarker of disease progression in the case of the donanemab trial, and in the Leqembi trial based on evidence of amyloid deposits. The Leqembi trial enrolled all comers that also included patients with earlier stages of early AD (low amyloid or low tau) in addition to intermediate and high amyloid/tau patients indicating a more advanced form of early AD. The donanemab trial included medium and high amyloid/tau patients implying intermediate to more advanced stages of early AD.8,9

The two trials were also designed with partly different efficacy endpoints. The donanemab study included as its primary endpoint the change in integrated Alzheimer’s Disease Rating Scale (iADRS) and Clinical Dementia Rating-Sum of Boxes, or CDR-SB. The Leqembi trial did not use iADRS as an efficacy endpoint, but used CDR-SB.8,9 Therefore, comparing the two trials can be challenging due to the different patient populations and the different endpoints.

Evaluation of the Phase 3 studies shows that efficacy is generally similar between Leqembi and donanemab when similar patient populations are compared for the same endpoints. The efficacy of donanemab as measured by CDR-SB is predominantly driven by patients with intermediate disease (intermediate tau) that show a 36% slowing of CDR-SB decline vs ~14% for high-tau patients.8,9 When the same (intermediate + high tau) patient subgroups are compared, Leqembi and donanemab are generally similar in efficacy as measured by percent slowing of cognitive decline.8,9

The efficacy of donanemab was most effective in AD patients that had milder disease and were younger, as determined by subgroup analysis. These patients had milder cognitive function loss and less tau pathology. Eli Lilly has planned a Phase 3 study in pre-clinical AD patients to capture milder disease in younger patients.

It should be noted that Leqembi or donanemab cannot repair the cognitive damage that has already occurred in AD patients, nor can it reverse the course of the disease or stop it from getting worse. However, the rate of decline in cognitive damage is measurably slowed down by targeting amyloid β clearance – therefore changing the course of the disease.

Table 1: Comparing Phase 3 trial early-AD efficacy measurements for Leqembi and donanemab. Clinical Dementia Rating-Sum of Boxes (CDR-SB) was used in the Leqembi CLARITY AD Phase 3 trial and the donanemab TRAILBLAZER-ALZ 2 Phase 3 trial. Within the same AD subpopulation (intermediate and high tau), the two antibodies are generally similar in efficacy as measured by CDR-SB. Donanemab does better in intermediate tau subpopulation – no comparator available with Leqembi in this subpopulation (adapted from reference 3,4,8,9).

Table 1: Comparing Phase 3 trial early-AD efficacy measurements for Leqembi and donanemab. Clinical Dementia Rating-Sum of Boxes (CDR-SB) was used in the Leqembi CLARITY AD Phase 3 trial and the donanemab TRAILBLAZER-ALZ 2 Phase 3 trial. Within the same AD subpopulation (intermediate and high tau), the two antibodies are generally similar in efficacy as measured by CDR-SB. Donanemab does better in intermediate tau subpopulation – no comparator available with Leqembi in this subpopulation (adapted from reference 3,4,8,9).

Safety data: Both Leqembi and donanemab target amyloid plaques via immunotherapy mechanisms – an antibody-based targeting of amyloid plaque that develops in AD. A consequence of this therapeutic approach is amyloid-related imaging abnormalities (ARIA), a term that encompasses a spectrum of MRI (neuroimaging) findings observed in patients receiving anti–amyloid beta immunotherapies for AD.7 These amyloid-targeting antibodies are known to cause brain swelling and bleeding as observed in ARIA – edema/effusion (ARIA-E) or microhemorrhages/superficial siderosis (ARIA-H) are observed.Therefore, ARIA is a safety issue that is carefully monitored for amyloid plaque targeting therapies.

There were three donanemab-related deaths in the Phase 3 clinical trial that were related to ARIA as detected by MRI imaging. There were three deaths in the Leqembi trial in patients, but those were related to patients on anticoagulant therapy.8,9 In general, the Phase 3 data shows that Leqembi has a superior safety profile compared to donanemab based on ARIA – see table below. Safety is where Leqembi has a distinct advantage over donanemab – the ARIA safety issue favors Leqembi.

Table 2: Safety favors Leqembi over donanemab. Amyloid-related imaging abnormalities (ARIA) were far more acute for donanemab. Note that the donanemab Phase 3 trial included 3 patient deaths related to ARIA (adapted from reference 3,4,8,9).

Table 2: Safety favors Leqembi over donanemab. Amyloid-related imaging abnormalities (ARIA) were far more acute for donanemab. Note that the donanemab Phase 3 trial included 3 patient deaths related to ARIA (adapted from reference 3,4,8,9).

FDA prescription has a Black Box warning: The FDA-approved Leqembi has a Black Box warning on the prescription label. We expect donanemab also to be approved with a Black Box warning, especially since the safety profile of Leqembi is superior to donanemab.

Measure of amyloid plaque clearance on treatment: The desired consequence of amyloid β targeting antibody therapy is clearance of amyloid deposits and reduction of the amyloid burden that contributes to the pathology in AD. A measure of amyloid plaque clearance was an important secondary endpoint in both the Leqembi and donanemab trials. Amyloid clearance was measured by positron emission tomography (PET) imaging. The early and significant changes in amyloid burden suggests that brain PET scans may provide a tool for clinical monitoring of the effect of therapy. Therapy with both antibodies showed significant amyloid clearance in treated patients compared to patients in the placebo arm (see Figures 3a and 3b).8,9

Figure 3A: Leqembi (lecanemab) treatment leads to amyloid plaque clearance as measured by PET scans in a sub-study that included 698 patients. Measured as change from baseline over 18 months (Van Dyck et al; Lecanemab in Early Alzheimer’s Disease; NEJM 388;1, 2023).

Figure 3A: Leqembi (lecanemab) treatment leads to amyloid plaque clearance as measured by PET scans in a sub-study that included 698 patients. Measured as change from baseline over 18 months (Van Dyck et al; Lecanemab in Early Alzheimer’s Disease; NEJM 388;1, 2023).

Figure 3B: Treatment with donanemab leads to amyloid clearance as measured by PET scans. Both sub populations of patients, intermediate (low/medium) tau) and intermediate + high (combined) tau showed similar amyloid clearance compared to baseline over 76 weeks (Sims et al; Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial; JAMA. doi:10.1001/jama.13239; 2023).

Figure 3B: Treatment with donanemab leads to amyloid clearance as measured by PET scans. Both sub populations of patients, intermediate (low/medium) tau) and intermediate + high (combined) tau showed similar amyloid clearance compared to baseline over 76 weeks (Sims et al; Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial; JAMA. doi:10.1001/jama.13239; 2023).

Aduhelm (aducanumab) controversy

Before Leqembi, Biogen/Eisai developed Aduhelm. Aduhelm was, at one time, slated to be the first targeted therapy for AD that could change the course of the disease — its development timeline was more advanced than Leqembi and donanemab. Aduhelm is a human monoclonal antibody that preferentially binds to aggregated beta-amyloid to reduce the number of beta-amyloid plaques and slow disease progression.10

As many investors may be aware, Aduhelm was evaluated in November 2020 by an FDA Advisory Committee which voted against approval, by a vast margin – 10 members voted against, and one was “uncertain.” The FDA usually heeds the advice of its Advisory Committee but is not bound by it. In June 2021 the FDA surprisingly approved Aduhelm based on an accelerated approval path, triggering significant debate about the controversial decision. The decision by the FDA was particularly notable given the resounding rejection by the Advisory Committee. Three members of the FDA Advisory Committee resigned over the FDA’s decision. The efficacy of Aduhelm was questionable and safety was also an issue.

Subsequently, Biogen and Eisai halted plans for approval in the EU after the EU regulators conveyed that approval was unlikely. With a hefty annual cost of $56K, even if FDA approved, the lack of enthusiasm with the advisory committee and the controversy surrounding the FDA approval made health insurers hesitant to cover cost. Aduhelm is not being marketed or developed further.

The bottom line

Both Leqembi and donanemab are pioneering antibody-based therapies that target amyloid β plaque formation in AD. Clearance of amyloid deposits and reduction of the amyloid burden can change the course of the disease as demonstrated in Phase 3 trials for both Leqembi and donanemab. Visible Alpha consensus shows that Leqembi is projected to capture a significantly larger market share than donanemab. Leqembi is expected to reach peak unadjusted revenues of $9.9 billion in 2034, and donanemab is expected to reach peak unadjusted revenues of $6.4 billion in 2032. Analyst estimates are driven by Leqembi’s superior safety profile over donanemab. Furthermore, an upcoming Leqembi version, if approved, could allow patients to self-inject at home using a subcutaneous auto-injector.


  1. Rajan et al; Population Estimate of People with Clinical AD and Mild Cognitive Impairment in the United States (2020–2060); Alzheimer’s Dement. 17 (12); 2021
  2. Alzheimer’s Disease International
  3. Eisai Company Presentation information (
  4. Eli Lilly Information;
  5. Alzheimer’s Association Treatments & Research | Alzheimer’s Association
  6. Busche & Hyman; Synergy between amyloid-β and tau in Alzheimer’s disease. Nature Neuroscience; 23, 1183–1193; 2020
  7. Roytman et al; Amyloid-Related Imaging Abnormalities: An Update; AJR:220, 2023
  8. Sims et al; Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial; JAMA. doi:10.1001/jama.13239; 2023
  9. Van Dyck et al; Lecanemab in Early Alzheimer’s Disease; NEJM 388;1, 2023
  10. Silvestro et al; Aducanumab and Its Effects on Tau Pathology: Is This the Turning Point of Amyloid Hypothesis? Int.J.Mol.Sci.,23,2011;2022

In our weekly round-up of the top charts and market-moving analyst insights: Memory chip makers are expected to see revenues decline in 2023; Pfizer’s (NYSE: PFE) Elrexfio marks the third bispecific antibody approved for multiple myeloma by the FDA; Lynas Rare Earths (ASX: LYC) is projected to experience a decline in revenue in 2023-24; and U.S. oil refiners are expected to see a decrease in gross profit per unit between 2023-2025.

Memory Chip Manufacturers to See Revenue Dip in 2023, Recovery from 2024 Onward

Memory chip makers, including SK hynix (KRX: 000660), Micron Technology (NASDAQ: MU), Nanya Technology (TWSE: 2408), and GigaDevice Semiconductor (SSE: 603986) are expected to see revenues decline in 2023, according to Visible Alpha consensus. The memory semiconductor industry is dealing with overcapacity and excess inventory coupled with sluggish demand. This has been placing downward pressure on average selling prices (ASP) of DRAM (Dynamic Random-Access Memory) and NAND memory technologies. Analysts expect both DRAM and NAND revenues to decline in 2023 as sluggish demand and high inventory eat into ASPs. However, these companies are expected to see revenue rebound starting in 2024 as the market potentially transitions towards undersupply.

Memory Chip Manufacturers to See Revenue Dip in 2023, Recovery from 2024 Onward

Pfizer Enters Race for Bispecific Antibody Treatment of Multiple Myeloma

Pfizer’s (NYSE: PFE) Elrexfio marks the third bispecific antibody approved for multiple myeloma by the FDA – Elrexfio was granted accelerated (conditional) approval by the FDA on August 14, 2023. The other two bispecific antibodies approved for multiple myeloma belong to Johnson & Johnson (NYSE: JNJ): Tecvayli (approved in October 2022) and Talvey (approved on August 10, 2023).

According to Visible Alpha consensus, analysts’ expectations for the probability of success of full approval for Elrexfio is 59%, reflecting the risk associated with a successful registration (Phase 3) trial for full approval. Visible Alpha consensus risk-unadjusted revenue projections of close to $1.8 billion in 2031 (peak) are significantly lower than PFE’s guidance of $4 billion in peak sales. Peak risk-adjusted revenue expectations in 2031 are $971M.

Elrexfio (elranatamab) is a bispecific antibody that targets B-cell maturation antigen (BCMA) and CD3 on T cells. Elrexfio is a T cell engager that activates T cells, which results in killing multiple myeloma tumor cells.

Pfizer Enters Race for Bispecific Antibody Treatment of Multiple Myeloma

Lynas Rare Earths to Face Revenue Slump Amid Price Volatility

Lynas Rare Earths (ASX: LYC), an Australian rare-earths mining and processing company, is projected to experience a decline in revenue in 2023-24, according to Visible Alpha consensus. This decline is primarily attributed to an expected decrease in revenue generated from neodymium and praseodymium (NdPr) oxide, which constituted 96% of the company’s total revenue in 2022. NdPr are essential components in the manufacturing of high-performance magnets that are used in electronics, electric and hybrid vehicles, and wind turbines, among others.

Prices of rare earth minerals have declined over the past year due to increased supply from China and softer demand from renewable energy companies and the automotive sector. Analysts anticipate that the lower average realized prices from NdPr will be key to pushing down revenue expectations between 2023-24. However, it is expected that revenues and, to a lesser extent, prices will rebound starting in 2025.

Lynas Rare Earths to Face Revenue Slump Amid Price Volatility

Gross Profit Per Unit for Leading U.S. Oil Refiners to Decline Along With Easing Crude Oil Prices

According to Visible Alpha consensus estimates, Phillips 66 (NYSE: PSX), Valero Energy (NYSE: VLO), Marathon Petroleum (NYSE: MPC), PBF Energy (NYSE: PBF), and HF Sinclair (NYSE: DINO) are projected to see a decrease in gross profit per unit between 2023-2025. U.S. refiners enjoyed bumper profits in 2021-22, as Western sanctions on Russia and COVID lockdowns in China crimped global fuel supplies at a time when demand was recovering from pandemic lows, creating increased demand for U.S. crude oil. In 2023, however, rising oil exports from Russia and China are expected to dampen the demand for U.S. crude derivatives.

The decline in profits is also partly due to the anticipated decline in crude oil prices during the forecast period. Lower crude oil prices translates to reduced prices for refined products, impacting margins for refiners. Crude oil prices are anticipated to decrease to an average of $78 per barrel (bbl) in 2023, down from the peak levels observed last year. Despite the decline, profits are generally still expected to maintain above pre-pandemic levels.

Gross Profit Per Unit for Leading U.S. Oil Refiners to Decline Along With Easing Crude Oil Prices

Eli Lilly (NYSE: LLY) plans to acquire DICE Therapeutics (NASDAQ: DICE) for approximately $2.4B in cash. This purchase price represents a share price of $48, which is around a 40% premium to the 30-day volume-weighted average trading price of DICE as of the last trading day before the June 2023 announcement date. The transaction is expected to close in Q3 2023. The acquisition is being driven by DICE’s innovation in oral drug development and its lead IL-17 inhibitor for psoriasis.

DICE has developed a medicinal chemistry technology platform that enables the development of small molecule drugs that can disrupt protein-protein interfaces (PPI). The first utility of this innovation is the development of oral inhibitors of already-validated targets for which biologic drugs administered systemically by injection are on the market.¹

DICE’s lead oral drug program targets interleukin-17 (IL-17) for psoriasis (plaque psoriasis), an autoimmune disease. Visible Alpha’s consensus revenue estimates project DICE’s oral IL-17 inhibitor will generate over $2B in global revenues in 2033 for psoriasis, based on approval in 2027. The program is currently in Phase 2 trials. According to Visible Alpha consensus, the probability of approval is 54% (the risk-adjusted consensus revenue estimate for 2033 is $959M).

Figure 1: Visible Alpha consensus revenue estimates project over $2B globally for DICE’s oral IL-17 inhibitor for psoriasis

Eli Lilly Plans to Acquire DICE Therapeutics for $2.4B

About IL-17

IL-17 is a proinflammatory cytokine that is important in mounting an immune response against infections. Under disease conditions or loss of immune regulation, IL-17 is released by immune cells and interacts with other proinflammatory cytokines to drive an unregulated and misdirected immune response. This misdirected immune response progresses the pathology of inflammatory and autoimmune diseases such as psoriasis, among others.²

LLY pipeline includes a biologics-based IL-17 inhibitor antibody on the market

LLY markets IL-17 inhibitor antibody Taltz (ixekizumab). Taltz was approved by the FDA in 2016 for moderate to severe plaque psoriasis and subsequently for other indications. Taltz is currently approved for plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and axial spondyloarthritis. In 2022, Taltz generated revenues of $2.48B across all indications. Besides Taltz, there are currently three other approved IL-17 inhibitor antibodies on the market. There is no oral IL-17 inhibitor approved at present.

Favorable market landscape for an oral IL-17 inhibitor

An oral IL-17 inhibitor with equal or better efficacy and safety would be favored over an IL-17 antibody that is injected. An oral IL-17 inhibitor is expected to improve patient compliance (which leads to improved efficacy) and can expand market share into the mild/moderate psoriasis disease segment of patients that are not yet on IL-17 injections or may be hesitant about choosing to take injections.

LLY made its decision based on robust preclinical data and proof-of-concept Phase 1 clinical studies in healthy volunteers and mild/moderate psoriasis patients. The data demonstrated encouraging efficacy and safety that matches or improves over currently marketed antibody-based IL-17 inhibitors.


Challenges in developing oral drugs that replace biologics administered by injection

Developing oral drugs to replace biologics-based drugs (antibodies, peptides, fusion proteins) that are administered by injection (parenterally) would be a major advance in therapeutic drug development. Biologics-based drugs are proteins and peptides that are quickly acted on by gastrointestinal enzymes — proteolytic enzymes that break down proteins into amino acids.

In the past, attempts at oral delivery of biologics were based on several approaches. These include enclosing the protein/peptide biologic drug within a protective lipid-based envelope or modification by chemical or biophysical approaches to prevent degradation by gastrointestinal enzymes³. However, even if the protein/peptide-based drug circumvents degradation by gastrointestinal enzymes, there is the risk of immune activation, especially if the protein/peptide resembles microbial origin.

Besides oral delivery, intranasal and inhaled delivery of smaller molecular weight protein drugs or peptides (such as insulin) are also an area of research and development. An inhaled insulin developed by Pfizer (Exubera) was approved by the FDA in 2006 for type 1 and type 2 diabetes. Exubera was a commercial failure due to lung function risk, hypoglycemia, and the need for constant monitoring — reflecting the challenges of protein/peptide drug delivery other than via injection.

DICE’s technology platform and business model is appropriately suited to developing oral small molecule inhibitors that disrupt PPI. DICE’s pipeline of small molecule oral drugs can potentially replace already marketed biologics administered by injection. For example, there are currently marketed antibodies directed against integrins and PD-1, aside from antibodies against IL-17.

The advantage of oral drug delivery over injections is obvious — patients do not want to be injected or self-inject. Additionally, there are significant advantages related to patient compliance that lead to improved efficacy and subsequently better outcomes.

DICE’s DELSCAPE technology platform

The DELSCAPE platform uses DICE’s expertise in medicinal chemistry. It leverages DNA-encoded libraries (DELs) in a proprietary manner that makes it possible to develop oral small-molecule drugs that block PPIs. The oral small-molecule drug delivery technology is based on designing and defining PPIs that can be blocked to prevent biological signaling pathways that progress diseases. Identification of such PPIs is important since typically PPIs involve large complementary binding domains that are not amenable to being blocked effectively by small molecules¹. DICE has overcome this challenge by identifying small-molecule inhibitors of PPIs that act at a distance away from the PPI interface by perturbing the structure of one of the PPI pairs.¹

The bottom line

The LLY acquisition of DICE enhances and complements its pipeline and provides an innovative technology platform to develop additional small-molecule oral drugs in the autoimmune and inflammatory space. The acquisition of DICE provides LLY with a discovery engine that develops oral drugs in therapeutic areas currently dominated by injectable drugs — an unmet need with large market potential.


  1. DICE Therapeutics Information
  2. Ge et al; Biology of Interleukin-17 and Its Pathophysiological Significance in Sepsis. Front. Immunol., 28 July 202
  3. Peachey; Moving towards oral delivery of biologics. European Pharmaceutical Review. February 2023


In our weekly round-up of the top charts and market-moving analyst insights: Novartis (NYSE: NVS) agrees to acquire Chinook Therapeutics (NASDAQ: KDNY); Lululemon Athletica (NASDAQ: LULU) projected to see significant international revenue growth; Rent the Runway (NASDAQ: RENT) subscribers and revenue expected to rise; Ford Motor’s (NYSE: F) Model e division (electric vehicles) to expand.

Novartis Agrees to Acquire Chinook Therapeutics and its Renal Pipeline

Novartis (NYSE: NVS) has agreed to acquire Chinook Therapeutics (NASDAQ: KDNY) for $3.2B up front, driven by Chinook’s innovative rare and severe kidney disease pipeline that will add to Novartis’ existing kidney disease focus. The acquisition is driven by Chinook’s lead program, atrasentan (currently in Phase 3 studies), a selective endothelin A receptor antagonist for IgA nephropathy. Visible Alpha consensus estimates show atrasentan ramping up to $1.25B in global revenue in 2032 ($932M on a risk-adjusted basis). Analysts peg the probability of regulatory approval at a consensus of 67.9%.

Novartis Acquisition; Lulu’s Global Growth; Rent To Rise; Ford’s Ev Sales

Analysts Anticipate Strong International Revenue Growth for Lululemon Athletica, Outpacing U.S. and Canada

Apparel retailer Lululemon Athletica (NASDAQ: LULU) is projected to see significant revenue growth in markets outside of the U.S. and Canada (UCAN). The company currently operates in UCAN, Europe, Asia, and Australasia. According to Visible Alpha consensus, the proportion of revenue generated internationally (excluding UCAN) is expected to increase from 15% in 2022 to 29% by 2027. Revenue outside of UCAN is expected to grow at a CAGR of 33% between 2022-27, and projected to reach $3.9 billion by 2027. Lululemon plans major expansion in its international markets, particularly in China. Analysts project Lululemon will add 49 new stores outside of UCAN in 2023, many of which will be in Asia.

Novartis Acquisition; Lulu’s Global Growth; Rent To Rise; Ford’s Ev Sales

Soaring Subscribers and Revenue to Propel Growth for Rent the Runway

Analysts are expecting strong subscriber growth for Rent the Runway (NASDAQ: RENT), a fashion rental service provider with 129K average active subscribers expected in 2023, according to Visible Alpha consensus. The company claims demand for workwear has been surging as more people return to the office. Analysts expect subscription and reserve rental revenue to grow by 45% in 2023 to $269 million, with projections reaching $404 million by 2026.

Novartis Acquisition; Lulu’s Global Growth; Rent To Rise; Ford’s Ev Sales

Ford’s Revised Business Segments Highlight EV Sales Growth

Ford Motor’s (NYSE: F) revised business segment classification — Ford Blue (gas and hybrid vehicles), Ford Model e (electric vehicles), and Ford Pro (commercial products and services) — has highlighted analysts’ projections for significant growth in revenue and units sold, specifically in the EV segment. Analysts project 63% revenue expansion for Ford’s Model e division in 2023, far surpassing the projected 3% growth for Ford Blue. Ford Model e units sold are projected to rise substantially from 96K units in 2022 to around 795K units by 2026.

Novartis Acquisition; Lulu’s Global Growth; Rent To Rise; Ford’s Ev Sales

Roche’s (SWX: ROG) Vabysmo is the newest therapy to be approved for wet AMD (age-related macular degeneration) and is poised to challenge the dominance of Eylea from Regeneron (NASDAQ: REGN) and Bayer (FRA: BAYN). Vabysmo’s advantage is a longer half-life leading to less frequent injections compared to Eylea, with generally equal efficacy. However, a high-dose version of Eylea, currently under FDA review, may blunt Vabysmo’s advantage.

Advantage of lower frequency of treatments

Lower frequency of intravitreal injections is an advantage as long as safety and efficacy are matched. Intravitreal injections are administered in the eyeball — not a pleasant experience for patients. Roche conducted two Phase 3 clinical trials with Vabysmo in wet AMD patients with a two-year endpoint that demonstrated that 59% and 67% of patients receiving Vabysmo treatments every four months achieved comparable vision gains versus Eylea, which is given every two months. Furthermore, an additional 15% and 14% achieved three-month dosing with comparable efficacy to Eylea in the two respective Phase 3 studies.

Besides high-dose Eylea and Vabysmo, other approaches to reduce injection frequency for wet AMD and other neovascular eye diseases are in clinical trials. Examples include Opthea’s (NASDAQ: OPT) OPT-302 in combination with Novartis’ (NYSE: NVS) Lucentis, and Ocular Therapeutix’s (NASDAQ: OCUL) OTX-TKI in combination with Eylea. These novel combination therapies add on to established treatments to extend durability of efficacy and reduce frequency of injections.

Improved version of Eylea

An improved version of Eylea at a higher dose is under FDA review and is expected to be approved in the summer of 2023. This long-lasting high-dose Eylea is formulated at 8 mg (versus 2 mg for the currently approved Eylea) and will be dosed every 3 to 4 months. Furthermore, it is comparable or even improved in safety and efficacy to Vabysmo. In Phase 3 pivotal trials, 79% and 77% of wet AMD patients on high-dose Eylea maintained vision gains demonstrating similar efficacy to the low-dose Eylea at 3 months and 4 months, respectively. Currently, there is no head-to-head data that compares Vabysmo with the high-dose version of Eylea.

Figure 1: Vabysmo and Eylea consensus revenue projections to 2032

Vabysmo and Eylea Chart New
Source: Visible Alpha consensus – May 23, 2023 (Note: Eylea sales revenue as recorded by Regeneron; Vabysmo sales revenue as recorded by Roche; Swiss franc figures for Vabysmo were converted to U.S. dollars at the prevailing exchange rate on May 23, 2023)

Consensus revenue projections for Vabysmo and Eylea

Visible Alpha’s analyst consensus projections depict Vabysmo initially gaining market share over Eylea, but ultimately high-dose Eylea holds its own. Revenues depicted include diabetic macular edema (DME), wet AMD, and other relevant neovascular ophthalmic indications. Note that declining Eylea revenues are also a function of Eylea biosimilars expected to be on the market after May 2024. Eylea’s composition-of-matter patent expires in June 2023 but its market exclusivity as a biologic has been extended through May 2024.

Given the significance of the high-dose Eylea Phase 3 pivotal data, it is perhaps surprising that analysts have not raised their forecasts further. Although some analysts have started to call out high-dose usage of Eylea specifically in their models, overall revenue forecasts have not changed significantly in the months since the Phase 3 study results were first reported in September 2022. Either analysts are more sanguine about the overall impact of the high-dose Eylea or are perhaps waiting for safety and efficacy confirmation from the FDA before making more substantive revisions. In either case, the June 27th 2023 target date for high-dose Eylea review set by the FDA could be a catalyst for further movement. In February of 2023, the FDA granted high-dose Eylea Priority Review, which allows for expedited review within six months.

Mechanisms of action for Vabysmo and Eylea

Vabysmo (faricimab) is a humanized bispecific antibody that inhibits two pathways by binding to vascular endothelial growth factor (VEGF-A) and angiopoietin-2 (Ang-2). Inhibition of VEGF-A suppresses endothelial cell proliferation, neovascularization, and vascular permeability. Inhibition of Ang-2 promotes vascular stability and desensitizes blood vessels to the proliferative effects of VEGF-A.

Eylea (aflibercept) is a recombinant fusion protein consisting of the human VEGF extracellular domain fused to the Fc portion of human immunoglobulin IgG1. Eylea inhibits VEGF-A, preventing the pathology driven by mitogenic, chemotactic, and vascular permeability factors that induce endothelial cell proliferation.

The bottom line

Both Vabysmo and the high-dose version of Eylea decrease the frequency of injection, which is a major benefit to patients. While Vabysmo and high-dose Eylea will be major players in the imminent wet AMD marketplace, we also anticipate novel therapeutics that reduce frequency of injections in combination with established therapies to make an impact in the years ahead. Furthermore, biosimilar Eylea will influence the Wet AMD market landscape as well. Over time, long-term safety and efficacy data and patient preference will determine market dynamics.

Drug approvals by the U.S. Food and Drug Administration (FDA) of next-generation glucagon-like peptide-1 (GLP-1) receptor agonists mark a new era for the treatment of type 2 diabetes (T2D) and obesity.

The four leading FDA-approved GLP-1 receptor agonist drugs, Mounjaro (Eli Lilly), Ozempic (Novo Nordisk), Wegovy (Novo Nordisk), and Rybelsus (Novo Nordisk) are forecasted to generate over $55 billion combined in 2030, based on Visible Alpha consensus revenue estimates.

This market potential driving GLP-1 receptor agonist drug revenues is supported by a more nuanced understanding of the biology underlying T2D and obesity along with innovation in GLP-1 receptor agonist drug development.

GLP-1 receptor agonists

The GLP-1 receptor agonists (also called GLP-1 agonists) class of drugs for T2D and obesity/weight loss have generated unusually broad interest among investors and even the general public. The next generation of GLP-1 agonist drugs — tirzepatide and semaglutide — are an improvement over first-generation GLP-1 agonist drugs — dulaglutide, liraglutide, and exenatide — and also superior to various other mechanistically distinct drugs for T2D.

The weight-loss efficacy of GLP-1 agonist drugs, more than their utility for T2D, is responsible for the heightened public interest. No other FDA-approved drug for obesity/weight loss has shown such therapeutic efficacy as the next-generation GLP-1 agonist class — tirzepatide and semaglutide. Furthermore, scientific and clinical data over the past few years point to the benefits of weight loss for T2D patients — primarily improvement of blood glucose control and cardiovascular benefits. To date, the GLP-1 agonist drugs are considered to be safe and have an acceptable tolerability profile.

Visible Alpha consensus revenue estimates for 2030 show Mounjaro leading the pack with $20.6 billion, Ozempic at $18.1 billion, Wegovy at $12.0 billion, and Rybelsus at $7.4 billion. As these next-generation GLP-1 agonist drugs ramp up, gain market share, and expand the market for T2D and obesity, the older GLP-1 agonist drugs such as Trulicity, Saxenda, and Victoza are expected to dwindle in market share. Of the GLP-1 agonists, Wegovy and Saxenda are the only two approved specifically for obesity/weight loss.

Background on GLP-1 and GIP biology

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are peptide hormones or incretins released by the gut in response to nutrients. This hormone pathway is a self-regulating feedback system connecting the gut with the brain, pancreas, and liver.

Upon nutrient intake, GLP-1 and GIP peptide hormones bind to their respective receptors (GLP-1 receptors and GIP receptors) on beta cells of the pancreas (beta cells produce insulin) and stimulate the secretion of insulin. The secreted insulin facilitates the uptake of glucose by peripheral tissues. At the same time, the release of glucagon by alpha cells of the pancreas is reduced, preventing an increase in blood glucose. Note that insulin and glucagon have opposing effects. Insulin allows uptake of glucose by tissues (muscle, fat, liver, etc.), and glucagon releases glucose in the blood.

GLP-1 and GIP are naturally released upon ingestion of nutrients to overcome high glucose levels (hyperglycemia after a meal) by increasing insulin secretion and reducing glucagon secretion (glucagon increases blood glucose, the opposite of insulin). This effect of GLP-1 and GIP reduces glucose fluctuations in the blood. GLP-1 and GIP receptors are present on the beta cells of the pancreas, as well as in the central nervous system (CNS) and gastrointestinal tract. Under normal conditions, the interaction of released GLP-1 and GIP hormones on GLP-1 receptors and GIP receptors on pancreatic beta cells, in the CNS, and the gastrointestinal tract leads to regulation of blood glucose, reduced appetite and delayed glucose absorption due to slower gastric emptying, i.e., a feeling of satiety.

The diminished activity of GIP and GLP-1 are pathophysiological features of T2D and obesity. Pharmacological intervention to restore GLP-1 and GIP biological activity in T2D and obesity patients with GLP-1 and GIP receptor agonist drugs is therefore therapeutic in treating T2D and obesity. The GLP-1 and GIP receptor agonist drugs act as peptide mimetics, i.e., they act as synthetic mimetics of natural GLP-1 and GIP that are diminished or inadequate in T2D and obesity.

GLP-1 and GIP receptor agonists drugs are peptides that mimic natural GLP-1 and GIP. The binding of GLP-1 agonists and GIP agonists drugs to their respective receptors to induce insulin secretion and decrease glucagon secretion are among several other biological processes that reduce appetite and positively affect glucose metabolism (see Figure 1).

ADC VA Obesity Diagram V

Source: Fisman & Tenenbaum, Cardiovascular Diabetology, volume 20: 225; 2021

Figure 1: The mechanism of action of GLP-1 agonists and GIP agonists. The example depicted above is that of a dual GLP-1 agonist and GIP agonist, tirzepatide (Mounjaro). Note that Mounjaro is the only dual GLP-1 agonist and GIP agonist approved. Ozempic, Rybelsus, Wegovy, and the remaining are exclusively GLP-1 agonists. (Adapted from Fisman & Tanenbaum, 2021, Cardiovascular Diabetology).

Mounjaro and Ozempic lead the pack

Eli Lilly’s Mounjaro leads the Visible Alpha 2030 consensus revenue estimates with $20.6 billion, followed closely by Novo Nordisk’s Ozempic at $18.1 billion. The steep ramp-up of Mounjaro from FDA approval in 2022 to $20.6 billion in estimated revenues in 2030 is notable. Mounjaro belongs to the tirzepatide class, a dual agonist targeting both GLP-1 and GIP pathways (as discussed above) that was approved in 2022 for T2D. Following in the footsteps of Mounjaro is Novo Nordisk’s Ozempic at $18.1 billion. Ozempic is a semaglutide targeting only GLP-1 and was approved in 2017. To date, both Ozempic and Mounjaro are only FDA-approved for T2D. Analysts expect Mounjaro approval for obesity in 2023.  However, both are likely used off-label for obesity/weight loss.

image ()

Figure 2: Visible Alpha consensus revenue estimates for leading GLP-1 receptor agonists for T2D and obesity: The next generation GLP-1 receptor agonists (Mounjaro, Ozempic, Wegovy, and Rybelsus) show a steady rise from 2023 through 2030, while the older generation GLP-1 receptor agonists, Trulicity and Saxenda, decline in revenues.

Note that Ozempic and Mounjaro are used off-label for obesity/weight loss since neither one is FDA approved for obesity yet. Mounjaro was granted FDA fast-track designation for obesity/weight loss in October 2022, and analysts expect FDA approval for obesity later this year. Mounjaro is the first and only drug to help patients lose more than 20% of their body weight (in non-T2D patients).

Wegovy, a semaglutide like Ozempic, is approved specifically for obesity and has consensus revenue estimated at $12.0 billion in 2030. It is assumed that off-label use of Ozempic for obesity will decline in the coming years as customers and patients move to Wegovy for obesity, as an inventory shortage is now resolved. Wegovy and Ozempic have the same active ingredient semaglutide but Wegovy is administered at a higher dose for obesity compared to Ozempic for T2D.

Rybelsus also has the same active ingredient as Wegovy and Ozempic but is developed as an oral formulation taken daily. It has a 2030 consensus revenue estimate of $7.4 billion. Mounjaro, Ozempic and Wegovy all consist of once-weekly subcutaneous injections.

The older generation makes way for the new

Within the GLP-1 agonist class, tirzepatide (Mounjaro) and the semaglutides (Ozempic, Rybelsus, and Wegovy) show increasing market penetration from 2024 through 2030, our selected timeline. On the other hand, the older generation GLP-1 agonists, liraglutide (Victoza and Saxenda), dulaglutide (Trulicity), and exenatide (Byetta and Bydureon) decline in projected market share from 2024 through 2030. This is expected since the semaglutides and tirzepatide have a significantly improved drug profile over the older generation GLP-1 agonists. Improvements in drug profile for T2D and obesity include increased efficacy (blood glucose regulation), safety, frequency of dosing, cardiovascular benefit, and more meaningful weight loss. 

Table Visible Alpha consensus revenue estimates for GLP agonist drugs approved for TD and obesity

(Source: Visible Alpha Estimates)

Table 1: Visible Alpha consensus revenue estimates for GLP-1 agonist drugs approved for T2D and obesity. 

Mounjaro and Ozempic lead the others. Only two GLP-1 drugs are approved specifically for obesity/weight loss: Wegovy and Saxenda.  Wegovy is a semaglutide, like Ozempic, but at a higher dose for obesity/weight loss, while Saxenda, approved for obesity in 2014, is a liraglutide like Victoza, but at a different dose for obesity/weight loss.

Factors underlying the impressive revenue projections for the GLP-1 agonist drug class

Though the GLP-1 agonists drug class has been around since 2005, the increased interest and lucrative revenue projections is a more recent phenomenon. Several underlying scientific, clinical and market factors over the last few years played a role in bolstering the utility and market potential of GLP-1 agonists for T2D and obesity as listed below.

Next-generation GLP-1 agonists have an improved drug profile: With the advent of the next-generation GLP-1 agonists semaglutide and tirzepatide improved efficacy, safety, and tolerability were observed for T2D and obesity/weight loss over the older GLP-1 agonists, liraglutide, dulaglutide and exenatide.

Improved dosage and delivery: Less frequent dosing from daily to weekly has driven broader patient compliance and increased market share. For example, once-daily Victoza (liraglutide) has been steadily replaced by once-weekly Ozempic (semaglutide). An oral semaglutide, Rybelsus, was recently approved which provides the patient with more options.

Innovation in pharmacotherapy of obesity: A crucial development in the last few years has been the innovation in obesity drug development leading to relatively safe and dramatically more effective drugs. For years, drugs for obesity were plagued with lack of meaningful efficacy and a challenging safety profile, especially related to cardiovascular risks.

Impressive efficacy in weight reduction: Next-generation GLP-1 agonists in the semaglutide class improves efficacy over liraglutide, and the most advanced next-generation GLP-1 agonist class, tirzepatide, improves efficacy over semaglutides.

  • Wegovy improves over Saxenda: Individuals who received Wegovy lost an average of 14.9% of their initial weight on Wegovy versus 2.4% for placebo. Wegovy is a semaglutide that improved over Saxenda, a liraglutide that had demonstrated an average loss of 5.2% of initial body weight compared to individuals who received placebo (Wilding et al; NEJM, 2021) (Lingvay et al; Lancet 2022).
  • Mounjaro improves over Wegovy: Individuals that received the highest 15mg dose of Mounjaro lost an average of 20.9% of their initial weight versus 3.1% in the placebo arm. Those on the 10mg dose of Mounjaro lost 19.5% of their initial weight versus 3.1% on placebo (Eli Lilly press release April 28, 2022).

Obesity management as a primary treatment goal for T2D: Obesity and T2D share pathophysiological mechanisms that lead to overlapping metabolic complications. As discussed above, GLP-1/GIP biology regulates insulin and glucagon via the pancreas (addressing glucose control in T2D), the gastrointestinal tract, and the CNS which leads to satiety or reduced appetite and weight loss. Obesity and diabetes are interlinked – the term “diabesity” is used to describe obesity and T2D which go hand in hand. Lingvay et al., (Lancet, 2022)  pointed out that: “Weight loss is known to reverse the underlying metabolic abnormalities of T2D and, as such, improve glucose control; loss of 15% or more of body weight can have a disease-modifying effect in people with type 2 diabetes, an outcome that is not attainable by any other glucose-lowering intervention.”

Conceptual change in treating T2D beyond glucose control: Treatment of T2D has undergone a conceptual change over the last few years with treatment objectives shifting to include a cardio-centric goal in addition to the long-held gluco-centric goal of regulating blood sugar. This has changed the landscape for treatment of patients with T2D. Professional societies (diabetes, endocrinology and cardiology) have responded to this paradigm shift by advocating for the use of GLP-1 agonists for T2D, further driving GLP-1 agonist revenues.

Reduced risk of cardiovascular disease with GLP-1 agonists: Results from cardiovascular outcome studies have demonstrated that GLP-1 agonist use leads to a robust and consistent reduction in atherothrombotic events, particularly in patients with established atherosclerotic cardiovascular disease. This is an important metric since T2D and obese patients are at increased risk for cardiovascular disease.

2022 Guidelines on T2D by the American Association of Clinical Endocrinology and the American Diabetes Association: Guidelines include recommendations for the use of GLP-1 agonist-based drugs for T2D. The positive benefits of GLP-1 agonists in reducing risks of cardiovascular disease, renal disease, liver fibrosis, and obesity, in addition to glycemic control, were important criteria for the recommendation.

High market demand for Wegovy and Ozempic for weight loss: The recent high demand for Wegovy, soon after its FDA approval, led to its short supply, which was helped by a contract manufacturer delay and significant off-label use (likely for cosmetic weight loss). Subsequently, given the shortage of Wegovy, many were prescribed the other semaglutide, Ozempic, off-label for weight loss (Wegovy is the same active ingredient as Ozempic formulated at a higher dose for obesity). This resulted in a short supply of Ozempic for T2D patients – the patients in actual medical need versus those using Ozempic for obesity or weight loss for cosmetic needs. This high demand for Ozempic resulted in a dramatic increase in Ozempic sales for Novo Nordisk starting in late 2021. Both Wegovy and Ozempic are marketed by Novo Nordisk.  

As a result, analysts revised Ozempic revenue estimates several times, as depicted in Figure 3 below, which shows revisions from January 2022 onward. This positive sentiment for Ozempic and next-generation GLP-1 agonists was also buoyed by the many other encouraging factors related to next-generation GLP-1 agonists and their utility in T2D and obesity, as discussed above.


Figure 3: Ozempic revenue estimates were revised upward several times by analysts as demand for Ozempic for obesity/weight loss increased dramatically due to Wegovy’s short supply related to manufacturing delays. Wegovy was launched in June 2021 and was approved specifically for obesity/weight loss, and is the same active ingredient (semaglutide) as Ozempic but formulated at a higher dose for obesity. Ozempic has been approved for T2D since 2017. Ozempic is not FDA-approved for obesity. 

Safety and tolerability of GLP-1 agonists

The most common adverse effects of GLP-1 agonists are gastrointestinal in nature nausea, vomiting, diarrhea, and constipation. Tolerability issues may develop in 40-70% of patients based on reports from clinical trials. These adverse events must be weighed against the superior glycemic control, weight loss, and cardiovascular benefits that GLP-1 agonists provide for T2D and obese patients. In general, the side effects are mild to moderate in intensity and transient for most patients, and usually easily managed. For obesity, however, higher doses of GLP-1 agonists are used and there is no long-term safety data with the higher doses. The use of GLP-1 agonist drugs for cosmetic loss of weight is of concern since individuals may not be monitored for adverse events or long-term risks. For weight reduction, GLP-1 agonists must be used constantly. If treatment is halted, patients will regain the lost weight.

The bottom line

The next generation of the GLP-1 agonist class of therapeutics marks a paradigm shift in the treatment of T2D and obesity. The overlapping metabolic dysfunction in T2D and obesity is appropriately addressed by modulating GLP-1 biology. The magnitude of the impact of GLP-1 agonist drugs in treating T2D and obesity can be gauged by the unusually large market potential. We expect constant innovation leading to several novel GLP-1 agonist drugs to emerge in the years ahead.



  1. Sheahan et al; An overview of GLP-1 agonists and recent cardiovascular outcomes trials. Postgraduate Medical Journal; Volume 96, Issue 1133, March 2020
  2. Sharma et al; Recent updates on GLP-1 agonists: Current advancements & challenges. Biomedicine & Pharmacotherapy; Volume 108, December 2018
  3. Jastreboff & Kushner; New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics. Annual Review of Medicine; Vol. 74:125-139, January 2023
  4. Nauck et al; GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art. Molecular Metabolism; Volume 46, April 2021
  5. Shaefer et al; User’s guide to mechanism of action and clinical use of GLP-1 receptor agonists. Postgraduate Medicine; Volume 127 (8), September 2015
  6. Marx et al; GLP-1 Receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 Diabetes. Circulation; 146:1882–1894; December 2022
  7. Lingvay et al; Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet 22;399 (10322); January 2022
  8. Wilding et al; Once-Weekly Semaglutide in Adults with Overweight or Obesity; New England Journal of Medicine; 384; March 2021
  9. Fisman & Tenenbaum; The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect. Cardiovascular Diabetology:  Vol 20; 225 November 2021
  10. Georgeo-Martinez et al; Clinical recommendations to manage gastrointestinal adverse events in patients treated with Glp-1 receptor agonists: a multidisciplinary expert consensus. Journal of Clinical. Medicine.12(1), 145; January 2023
  11. Eli Lilly news release April 28, 2022:

In our weekly round-up of the top charts and market-moving analyst insights: Mobileye (MBLY) could double Advanced Driver-Assistance Sales (ADAS) over the next few years; Formula One Group (FWONA) is expected to see sales growth accelerate as the sport increases its number of races per season; Franco Nevada (FNV) may see gold production peak in 2025; and data pointing to the therapeutic efficacy of GLP-1 agonists for type 2 diabetes and obesity have raised future estimates for Novo Nordisk’s (NVO) Ozempic.

Mobileye Advanced Driver-Assistance Sales to Double Over Next Few Years, Say Analysts

Mobileye (MBLY) is forecasted to see Advanced Driver-Assistance Sales (ADAS) double over the next few years, according to Visible Alpha consensus. Many analysts believe demand for automobile chips will remain strong as more car manufacturers adopt ADAS features into their vehicles.

Mobileye MBLY ADAS sales Copy

Formula 1 Sales Growth Expected To Accelerate As New Races Are Added

Analysts expect Liberty Formula One (FWONA) will see sales growth accelerate this year as the sport adds more races to extend the season and benefits from higher attendance and advertising revenue. With the addition of the Las Vegas Grand Prix, the 2023 season will feature 23 races, up from 22 in 2022. According to Visible Alpha consensus, the company is expected to add a 24th race next year.

F Revenue by segment

Franco Nevada’s Gold Production Estimated to Peak in 2025, According to Analysts

Franco Nevada’s (FNV) gold production is forecasted by analysts to peak in 2025, according to Visible Alpha consensus. The company recently provided guidance suggesting slight growth in precious metal production through 2027, from current levels, if four new mines become functional.

FNV Franco Nevada Gold Production Peak

Analysts Hike Sales Estimates for Novo’s Ozempic by More Than 2x Since 2022

Analysts have raised future estimates for Novo Nordisk’s (NVO) Ozempic sales by more than 2x since last year driven by scientific & clinical data pointing to the therapeutic utility of GLP-1 agonists for type 2 diabetes and obesity. The increased market demand is predominantly for obesity and weight loss.

NOV Novo Nordisk Ozempic

In our weekly round-up of the top charts and market-moving analyst insights: CRISPR’s (CRSP) new gene-editing therapy is expected to be evaluated by the FDA; franchise sales are expected to drive growth for Xponential Fitness (XPOF); Alibaba (BABA) announces a new organizational structure; Winnebago (WGO) is poised to sell fewer units but at higher prices this year; and analysts continue to cut forecasts for deposits at Schwab (SCHW) Bank.

Read more

Wet age-related macular degeneration (AMD) is an area of intense drug development focus, given the large markets and unmet need. Innovation in wet AMD drug development threatens current market leaders and the standard of care.

Here, we briefly summarize wet AMD markets and discuss recent clinical data from two emerging players in the wet AMD landscape, Opthea and Ocular Therapeutix. We also provide consensus revenue projections for Opthea’s and Ocular Therapeutix’s drugs to contrast with projections for the market leader, Regeneron’s Eylea. Visible Alpha consensus shows declining Eylea revenue estimates in the next several years due to the emergence of new drugs like those from Opthea and Ocular Therapeutix.

Background on age-related macular degeneration

Macular degeneration results from damage to the macula, the part of the eye in the center of the retina responsible for central vision and the ability to see fine details clearly. Dry Age-Related Macular Degeneration (AMD), the early form of AMD, accounts for 90 percent of diagnosed cases. Wet (exudative or neovascular) AMD, the more advanced form, accounts for approximately 10 percent of cases but results in 90 percent of legal blindness. It’s the most common cause of visual impairment among elderly patients in developed countries.

Here’s more about wet AMD and its treatment:

Read more