Don’t look now, but most of Lilly’s up-and-coming drugs have nothing to do with diabetes.
By Joshua Slatko • [email protected]
Lilly Corporate Center
Indianapolis, IN 46285
OUTCOMES CREATIVITY INDEX SCORE: 29
Manny Awards — 5
Cannes Lions — N/A
Clio Health — 5
Creative Floor Awards — 12
MM+M Awards — 6
One Show — 1
(All figures are in millions of dollars, except EPS.)
Net income $6,194
Diluted EPS $6.79
R&D expense $6,086
Net income $2,746
Diluted EPS $3.01
R&D expense $3,358
(All sales are in millions of dollars.)
Jardiance family $1,154
COVID-19 antibodies $959
Jardiance family $669
Eli Lilly has long been known as a, or the, diabetes company. And with Trulicity still the world’s best-selling diabetes product, at the top of the company’s portfolio, it still is. But further down the list of Lilly’s growth leaders one finds products unrelated to diabetes. The company’s leading autoimmune drug, Taltz, enjoyed nearly one-third growth in 2020 and beat out a long list of competitors, including Humira, in a real-world analysis of patients with plaque psoriasis announced this past April. The Jardiance family of diabetes products crossed the blockbuster barrier in 2020 and earned a new indication in the cardiovascular area from FDA in August. The oncologic Verzenio is also closing in on blockbuster status and should earn it during 2021. And Lilly’s COVID-19 antibodies, bamlanivimab and etesevimab, earned the company more than $1.8 billion in sales from a standing start between when FDA granted bamlanivimab an Emergency Use Authorization in November 2020 through the end of June 2021. Products like Humalog, Humulin, and Basaglar may still be a big part of today’s Lilly, but tomorrow’s Lilly will clearly look quite different.
“We finished  with strong momentum in our core business areas, as volume-based revenue growth for our newest medicines and initial sales of our COVID-19 antibody therapy, coupled with our ongoing productivity agenda, drove robust margin expansion and solid earnings growth,” said David A. Ricks, Lilly’s chairman and CEO, in the company’s fourth-quarter earnings announcement.
Lilly’s top-line revenue in 2020 was $24.54 billion, an improvement of 9.9 percent over the previous year. Net income, though, declined by 25.5 percent to $6.19 billion and earnings per share were down by $2.10 to $6.79. This outcome, though, was impacted by the $3.7 billion gain recognized on the disposition of Elanco in 2019; without this and other one-time items, company leaders estimated that net income would have grown by 30 percent. In the first half of 2021, Lilly’s top-line revenue rose another 19.3 percent to $13.55 billion, while net income declined 4.3 percent to $2.75 billion and earnings per share were down 14 cents to $3.01. Lilly executives are projecting full-year 2021 EPS to fall between $6.73 and $6.93.
Partnerships & Acquisitions
In January, Lilly and Asahi Kasei Pharma Co. announced a license agreement whereby Lilly would acquire the exclusive rights for AK1780 from Asahi Kasei Pharma. AK1780 is an orally bioavailable P2X7 receptor antagonist that completed Phase I single and multiple ascending dose and clinical pharmacology studies. P2X7 receptors have been consistently implicated in neuroinflammation, a driving force in chronic pain conditions. Under the terms of the agreement, Lilly is responsible for future global development and regulatory activities for AK1780. Asahi Kasei Pharma retains the right to promote AK1780 in Japan and China (including Hong Kong and Macau).
Also in January, Lilly and Merus N.V., a clinical-stage oncology company developing multi-specific antibodies, announced a research collaboration and exclusive license agreement that will leverage Merus’ proprietary Biclonics platform along with the scientific and rational drug design expertise of Loxo Oncology at Lilly to research and develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies. Under the terms of the agreement, Merus will lead discovery and early-stage research activities while Loxo Oncology at Lilly will be responsible for additional research, development and commercialization activities.
In February, Lilly and Welldoc Inc. announced a collaboration and licensing agreement to integrate Welldoc’s software into Lilly’s connected insulin solutions, currently in development. Under the terms of the agreement, Lilly and Welldoc will collaborate to create a new version of the BlueStar insulin management solution that integrates insulin dosing data for several Lilly insulins. Lilly will commercialize the pen platform, which will include the new app and Lilly’s connected insulin pen solutions.
The new app will integrate insulin dosing data for several Lilly insulins. In the first version of the pen platform, a data transfer module will attach to the top of a prefilled, disposable insulin pen. When paired with the compatible app, the module will automatically transfer insulin dosing data. Lilly is also developing a fully disposable connected insulin pen to be used in future versions of the platform. The app will aggregate various dimensions of personalized data and connect with healthcare providers to deliver actionable insights and provide new opportunities to optimize diabetes care. Lilly plans to submit to the FDA in 2021 for the data transfer module, and Welldoc plans to submit to the FDA in 2021 for the new app.
Also in February, Lilly and Rigel Pharmaceuticals Inc. announced a global exclusive license agreement and strategic collaboration to co-develop and commercialize Rigel’s R552, a receptor-interacting serine/threonine-protein kinase 1 inhibitor, for all indications including autoimmune and inflammatory diseases. Pursuant to the collaboration, Lilly will lead all clinical development of brain penetrating RIPK1 inhibitors in central nervous system diseases. Rigel’s lead RIPK1 inhibitor, R552, has completed Phase I clinical trials and will begin Phase II clinical trials in 2021 as part of the collaboration. Rigel also has ongoing pre-clinical activities with its lead CNS penetrant RIPK1 inhibitor candidates.
Lilly and Rigel are jointly developing R552 at specified contribution levels. Lilly will be responsible for all costs of global commercialization for R552, and Rigel will have the right to co-commercialize R552 in the United States. Lilly will be solely responsible for all clinical development and commercialization of brain penetrating RIPK1 inhibitors in CNS indications.
During March, Lilly and Biolojic Design Ltd., a biotechnology company that computationally designs functional antibodies, announced a research collaboration and license agreement that will leverage Biolojic’s AI-based multibody platform to discover and develop a potential novel antibody-based therapy for the treatment of diabetes. A multi-specific antibody, or multibody, is a human antibody that is computationally engineered to bind two or more targets at each of its arms.
During May, Lilly and MiNA Therapeutics Ltd., a pioneer in RNA activation therapeutics, announced a global research collaboration to develop novel drug candidates using MiNA’s proprietary small-activating RNA technology platform. Under the terms of the agreement, MiNA will utilize its saRNA platform to research up to five targets selected by Lilly that aim to address diseases across Lilly’s key therapeutic focus areas. Lilly is responsible for preclinical and clinical development of candidates and will retain exclusive commercialization rights for any products resulting from the collaboration.
In July, Lilly and Kumquat Biosciences announced an exclusive collaboration focused on the discovery, development and commercialization of potential novel small molecules that stimulate tumor-specific immune responses. Through the multi-year collaboration, Kumquat will utilize its small-molecule immuno-oncology platform to discover novel clinical candidates and Lilly has the option to select a certain number of drug candidates for further development and commercialization worldwide, excluding Greater China. Kumquat has retained development and commercialization rights in Greater China for each of the drug candidates selected by Lilly, subject to Lilly’s option to co-commercialize in Greater China. Additionally, Kumquat has the option to co-develop and co-commercialize a certain number of the drug candidates selected by Lilly in the United States.
Also in July, Lilly and Banner Alzheimer’s Institute announced a strategic research collaboration as part of the planned Phase III, randomized, placebo-controlled study evaluating donanemab in participants at risk for cognitive and functional decline related to Alzheimer’s disease (TRAILBLAZER-ALZ 3). TRAILBLAZER-ALZ 3 is evaluating whether treatment with donanemab can slow the clinical progression of Alzheimer’s disease in trial participants. As part of the collaboration, Banner is leveraging its expertise and proven leadership in Alzheimer’s prevention trials, and support enrollment of trial participants with and without the e4 type of the apolipoprotein E (APOE4) gene through the Alzheimer’s Prevention Registry’s GeneMatch program.
That same month, Lilly announced the acquisition of Protomer Technologies, a private biotechnology company. Protomer’s proprietary peptide- and protein-engineering platform is used to identify and synthesize molecules that can sense glucose or other endogenous modulators of protein activity. The potential value of the transaction is more than $1 billion, with successful achievement of future development and commercial milestones. Lilly previously led an equity investment in Protomer alongside the JDRF T1D Fund, providing Lilly with 14 percent ownership of the company. Lilly is acquiring the remainder of the stock of Protomer beyond its initial investment.
During August, Lilly and Lycia Therapeutics Inc. announced a multi-year research collaboration and licensing agreement focused on the discovery, development, and commercialization of novel targeted therapeutics using Lycia’s proprietary lysosomal targeting chimera, or LYTAC, protein degradation technology. Lycia uses its next-generation degradation approach to target the untapped extracellular proteome, including cell surface receptors and secreted proteins. The LYTAC platform may enable the development of several therapeutic modalities, including antibodies and small molecules, with the potential to inhibit many targets previously considered intractable across a spectrum of therapeutic areas and diseases.
Under the terms of the agreement, the companies will utilize Lycia’s LYTAC platform to discover and develop novel degraders for up to five targets that aim to address key unmet medical needs in Lilly’s therapeutic areas of focus, including immunology and pain. Lilly is solely responsible for preclinical and clinical development of candidates and receives an exclusive worldwide license to commercialize potential medicines resulting from the agreement.
Trulicity crossed the $5 billion sales barrier for the first time in 2020, retaining its title as the world’s best-selling diabetes drug while earning $5.07 billion for Lilly, an improvement of 22.8 percent. Trulicity sales increased 22 percent in the United States, driven by increased volume, partially offset by lower realized prices primarily due to higher contracted rebates. Sales outside the United States increased 27 percent, primarily driven by increased volume. In the first half of 2021, sales of Trulicity rose another 21.5 percent to $2.99 billion.
The autoimmune medicine Taltz enjoyed an impressive 31 percent sales jump to $1.79 billion in 2020. U.S. sales were $1.29 billion, an increase of 27 percent, primarily driven by increased demand. Sales outside the United States was $500 million, an increase of 43 percent, primarily driven by increased volume. In the first half of 2021, sales of Taltz rose another 15.9 percent to $972 million.
In April, Lilly announced clinical trial meta-analysis and real-world evidence showing that Taltz demonstrated greater success in key measured treatment outcomes compared to other biologics in adults with moderate to severe plaque psoriasis. In the first one-year network meta-analysis based on area under the curve, Taltz showed numerically greater cumulative benefits on completely clear skin over one year compared to seven other biologics, as measured by Psoriasis Area Severity Index 100. In three real-world analyses of U.S. claims data ranging from one to three years, patients treated with Taltz stayed on treatment longer, were more adherent to the prescription and had more days on monotherapy compared to the other biologics studied.
In the network meta-analysis to assess the cumulative clinical benefits of biologics in psoriasis, using PASI 100 to measure the early and sustained effect of biologic medications approved for psoriasis over one year, Taltz offered patients with psoriasis the greatest number of cumulative days of completely clear skin compared to adalimumab (Humira), brodalumab (Siliq), etanercept (Enbrel), guselkumab (Tremfya), risankizumab (Skyrizi), secukinumab (Cosentyx), and ustekinumab (Stelara). In this analysis, Taltz showed one to 18 more cumulative weeks of completely clear skin over one year compared to these seven other biologics.
People with psoriasis taking Taltz achieved greater success taking medication as prescribed (adherence) and staying on medication for the prescribed duration (persistence), without needing additional medications (monotherapy), compared to those taking secukinumab, ustekinumab, adalimumab, and etanercept up to three years. Patients on Taltz stayed on treatment an observed median of nearly 22 weeks longer versus all other biologics pooled (414 versus 259 days) and approximately 11 to 34 weeks longer versus individual treatments: secukinumab (335 days), adalimumab (301 days), etanercept (181 days), and ustekinumab (176 days). Compared with the pooled set of other biologics where patients stayed on prescription for less than half of the year (45.7 percent), patients on Taltz took treatment as prescribed for over half of the year (53.2 percent), as measured by proportion of days covered by prescribed treatment. Patients taking Taltz also experienced more time (52.7 percent of the year) on monotherapy compared to the pooled set of other biologics (44.8 percent of the year).
In June, Lilly presented new data from Phase III studies that further demonstrated the long-term efficacy and safety profile of Taltz among patients with axial spondyloarthritis. In COAST-Y, Taltz showed consistent and sustained long-term improvements in signs and symptoms, functionality and quality of life in patients with r- and nr-axSpA. In this study, more than half of patients (56.7 percent) treated continuously with Taltz (80 mg every four weeks) through two years achieved Assessment of SpondyloArthritis international Society 40 percent response (ASAS40).
Among those treated continuously with Taltz every four weeks for two years, 43.9 percent of patients achieved low disease activity status, as measured by Ankylosing Spondylitis Disease Activity Score <2.1. Mean change from baseline (3.9) in ASDAS score was -1.6. Lilly says 19.7 percent achieved ASAS partial remission status. Mean change from baseline (6.6) in Bath Ankylosing Spondylitis Functional Index was -2.8. Mean change from baseline (33.9) in Medical Outcomes Survey Short Form 36 Physical Component Summary (SF-36 PCS) was 8.4.
An analysis of two Phase III studies in r-axSpA (COAST-V and COAST-W) and the long-term extension trial (COAST-Y), found that nine out of 10 patients treated with Taltz (89.6 percent) did not show radiographic progression for up to two years, as measured by mean change from baseline of modified Stoke Ankylosing Spondylitis Spinal Score <2. Overall mean rates of progression were low among patients treated with Taltz. These results were similar among patients who were previously treated with anti-TNF therapy (88 percent) and those who had not previously been treated with a biologic (91 percent).
The Jardiance family of diabetes products crossed the blockbuster barrier for the first time in 2020, growing sales by 22.2 percent to $1.15 billion. U.S. sales increased 10 percent, driven by increased volume, while sales outside the United States rose 41 percent, driven primarily by increased volume. In the first half of 2021, Jardiance family sales were up another 26.2 percent to $669 million.
In August, FDA approved Jardiance to reduce the risk of cardiovascular death plus hospitalization for heart failure in adults with heart failure with reduced ejection fraction. This approval was based on results from the EMPEROR-Reduced Phase III trial, which investigated the effect of adding Jardiance 10 mg versus placebo to standard of care in a broad range of 3,730 adults with and without type 2 diabetes who had heart failure (functional class II, III or IV) and a left ventricular ejection fraction of 40 percent or less. In the trial, Jardiance significantly reduced the relative risk of the primary composite endpoint of time to cardiovascular death or hospitalization for heart failure by 25 percent versus placebo. These results were seen regardless of background heart failure standard of care treatments.
In September, FDA granted Breakthrough Therapy designation for Jardiance as an investigational treatment for adults with heart failure with preserved ejection fraction. The decision was based on results from the landmark EMPEROR-Preserved Phase III trial, in which Jardiance demonstrated a 21 percent relative risk reduction for the composite primary endpoint of cardiovascular death or hospitalization for heart failure in adults with heart failure with preserved ejection fraction compared with placebo. The benefit was independent of ejection fraction or diabetes status. HFpEF accounts for about half of the more than 6 million heart failure cases in the United States. No currently approved treatments have been clinically proven to significantly improve outcomes specifically for people with HFpEF.
The oncologic Verzenio enjoyed a healthy sales bounce of 57.4 percent in 2020, bringing in $913 million. Sales increased 36 percent in the United States, driven by increased demand and, to a lesser extent, higher realized prices. Sales outside the United States more than doubled, driven by higher volume. In the first half of 2021, sales of Verzenio rose another 53.7 percent to $610 million.
In June, Lilly announced new data for the investigational use of Verzenio in high risk early breast cancer from an exploratory analysis from the positive Phase III monarchE trial evaluating Verzenio in a subgroup of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high risk early breast cancer who had received neoadjuvant chemotherapy.
In an exploratory analysis of a pre-specified subgroup of patients who received neoadjuvant chemotherapy, the addition of Verzenio to endocrine therapy resulted in a numerically greater effect size when compared to the intent-to-treat population. Treatment with Verzenio in combination with standard adjuvant ET decreased the risk of breast cancer recurrence in these patients by 38.6 percent compared to ET alone. This corresponds to a 6.6 percent difference in the two-year rate of invasive disease-free survival between arms (87.2 percent in the Verzenio plus ET arm compared to 80.6 percent in the ET only control arm). The addition of Verzenio to ET also reduced the risk of developing metastatic disease by 39 percent. This corresponds to a 6.7 percent difference in two-year distant relapse-free survival rates – or time to developing breast cancer that has spread to other parts of the body – between the arms (89.5 percent in the Verzenio plus ET arm compared to 82.8 percent in the ET only control arm).
After earning an emergency use authorization for the treatment of COVID-19 in November 2020, the monoclonal antibody bamlanivimab generated $871 million in sales for Lilly through the end of the year. In the first half of 2021, bamlanivimab and its partner COVID drug etesevimab generated sales of $959 million.
FDA granted Emergency Use Authorization in February for investigational bamlanivimab 700 mg and etesevimab 1400 mg together for the treatment of mild to moderate COVID-19 in patients aged 12 and older who are at high risk for progressing to severe COVID-19 and/or hospitalization. The EUA was based on Phase III data from the BLAZE-1 trial, which demonstrated bamlanivimab and etesevimab together reduced the risk of COVID-19 hospitalizations and death by 70 percent. These data replicate earlier results in a much larger group of patients. Additionally, the outcomes seen with bamlanivimab and etesevimab together are consistent with the reduction in risk of hospitalization or ER visits seen with bamlanivimab alone.
In March, Lilly announced new data from the randomized, double-blind, placebo-controlled BLAZE-1 Phase III study, demonstrating bamlanivimab 700 mg and etesevimab 1400 mg together significantly reduced COVID-19 related hospitalizations and deaths in high-risk patients recently diagnosed with COVID-19. This new Phase III cohort of BLAZE-1 included 769 high-risk patients, aged 12 and older with mild-to-moderate COVID-19. Bamlanivimab and etesevimab together also demonstrated statistically significant improvements on key secondary endpoints. These results are consistent with those seen in other data sets from BLAZE-1; in the previous Phase III cohort, bamlanivimab 2800 mg with etesevimab 2800 mg reduced the risk of hospitalizations and deaths by 70 percent and in the Phase II cohort, bamlanivimab alone reduced the risk of hospitalizations and ER visits by approximately 70 percent. The viral load reductions were also consistent with what was observed in the previous Phase III cohort of the study.
During that same month, Lilly, Vir Biotechnology Inc., and GlaxoSmithKline plc announced topline data from the expanded Phase II BLAZE-4 trial studying low-risk adult patients with mild to moderate COVID-19. Results showed that investigational bamlanivimab 700 mg co-administered with VIR-7831 500 mg demonstrated a 70 percent relative reduction in persistently high viral load (> 5.27; cycle threshold value < 27.5) at day 7 compared to placebo, meeting the primary endpoint.
In April, Lilly asked FDA to revoke the Emergency Use Authorization for bamlanivimab 700 mg alone. Lilly made this request due to the evolving variant landscape in the United States and the full availability of bamlanivimab and etesevimab together. This final step in Lilly’s transition to only supply bamlanivimab and etesevimab for administration together in the United States for the treatment of COVID-19 – as planned with FDA – follows the modification of contracts with the U.S. government to ensure adequate supply of etesevimab to be used together with bamlanivimab. Lilly developed bamlanivimab and etesevimab for administration together to meet the potential challenge of treatment-resistant variants likely to resist treatment with either monoclonal antibody used alone.
In September, FDA expanded the Emergency Use Authorization for bamlanivimab 700 mg and etesevimab 1400 mg administered together to include post-exposure prophylaxis in certain individuals for the prevention of SARS-CoV-2 infection. The neutralizing antibodies can now be used together to treat high-risk individuals 12 years of age and older who have not been fully vaccinated against COVID-19 or are not expected to mount an adequate immune response to complete vaccination, and have been exposed to someone infected with SARS-CoV-2 or who are at high risk of exposure in an institutional setting, including a nursing home or prison.
The expanded authorization was based on data from BLAZE-2, a study conducted in partnership with the National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health) and the COVID-19 Prevention Network, that enrolled residents and staff at U.S. long-term care facilities (commonly referred to as nursing homes). In this placebo-controlled Phase III study, bamlanivimab 4200 mg reduced the risk of contracting symptomatic COVID-19 by up to 80 percent in nursing home residents and up to 57 percent among residents and staff of long-term care facilities.
The autoimmune drug Olumiant generated $639 million in sales for Lilly, an improvement of 49.6 percent over the previous year. In the first half of 2021, Olumiant sales rose another 41.1 percent to $402 million.
In April, Lilly and partner developer Incyte announced new analyses of the BREEZE-AD5 Phase III clinical trial data and an extended safety analysis across multiple trials showing that Olumiant 2-mg tablet taken once daily showed improvement in key measured treatment outcomes compared to placebo, and helped further characterize the long-term safety profile in adults with moderate to severe atopic dermatitis. In one BREEZE-AD5 analysis, Olumiant provided concurrent improvements in the severity and extent of AD, other key symptoms and quality of life as early as one week, as measured by percent change from baseline compared to placebo. In a separate BREEZE-AD5 analysis, adults with AD on 10-50 percent of their bodies at baseline who were treated with Olumiant showed significant improvements in the severity and extent of disease compared to placebo.
Also in April, Lilly and Incyte announced results from a second Phase III trial (BRAVE-AA1) evaluating the efficacy and safety of once-daily Olumiant 2-mg and 4-mg in adults with severe alopecia areata. The data are consistent with findings from the first Phase III clinical trial, BRAVE-AA2, top-lined earlier in the year. In both investigational trials, a statistically significant proportion of patients treated with Olumiant achieved the primary endpoint of hair regrowth across the two dosing regimens at Week 36 compared to patients treated with placebo. In both studies, over the nine-month treatment period, patients with severe AA treated with Olumiant 2-mg and 4-mg doses experienced significantly greater scalp hair regrowth compared to patients treated with placebo based on physician’s assessment.
Also in April, Lilly and Incyte announced results of COV-BARRIER, a Phase III study evaluating Olumiant 4 mg once daily plus standard of care versus placebo plus SoC. The trial did not meet statistical significance on the primary endpoint, which was defined as a difference in the proportion of participants progressing to the first occurrence of non-invasive ventilation including high flow oxygen or invasive mechanical ventilation including extracorporeal membrane oxygenation or death by Day 28. Olumiant-treated patients were 2.7 percent less likely than those receiving standard of care to progress to ventilation (non-invasive or mechanical) or death, a difference that was not statistically significant.
In June, Lilly and Incyte presented data from post-hoc analyses that suggested Olumiant 4 mg tablet reduced pain and duration of morning joint stiffness, and improved overall physical function at 12 weeks, among patients with moderate to severe rheumatoid arthritis, compared to Humira and placebo. In a post-hoc analysis of the Phase III RA-BEAM study, patients treated with Olumiant 4 mg saw greater improvements in pain relief and physical function, as well as reduced duration of morning joint stiffness, at 12 weeks compared to Humira and placebo. These differences in pain relief were not influenced by disease activity during treatment. In this analysis, improvements in fatigue with Olumiant 4 mg were greater than with placebo and similar to Humira after 12 weeks of treatment.
In July, FDA broadened the Emergency Use Authorization for Olumiant to allow for treatment with or without remdesivir, whereas the EUA was previously restricted to use only in combination with remdesivir. The EUA now provides for the use of Olumiant for treatment of COVID-19 in hospitalized adults and pediatric patients 2 years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.
FDA based its decision on data from the Phase III COV-BARRIER study. COV-BARRIER was a randomized, double-blind, placebo-controlled study of hospitalized patients comparing Olumiant 4 mg once daily plus standard of care versus placebo plus standard of care. While the composite primary endpoint of COV-BARRIER, which was defined as a difference in the estimated proportion of participants progressing to non-invasive ventilation including high flow oxygen or invasive mechanical ventilation (including ECMO) or death by Day 28, did not meet statistical significance, Olumiant-treated patients (27.8 percent) were less likely than those receiving standard of care (30.5 percent) to progress to ventilation or death.
That same month, Lilly and Incyte announced that FDA would not meet the Prescription Drug User Fee Act action date for the supplemental new drug application for Olumiant for the treatment of adults with moderate to severe atopic dermatitis. The delay is related to FDA’s ongoing assessment of JAK inhibitors.
Sales of the migraine drug Emgality more than doubled in 2020, from $163 million to $363 million. In the first half of 2021, Emgality sales rose another 70.4 percent to $276 million.
In June, Lilly announced that the company would be conducting a head-to-head study comparing once-monthly injectable Emgality with Nurtec ODT, an orally disintegrating tablet patients take every other day. CGRP is a protein in the brain thought to play a key role in migraine. Emgality binds to this protein, preventing it from attaching to the CGRP receptors, whereas Nurtec ODT blocks the receptor for this protein. This study aims to answer important questions that will help clinicians and patients make more informed treatment decisions on the path to more migraine-free days.
The study, which will be the first head-to-head clinical trial comparing two medications targeting CGRP, is a multi-site, randomized, double-blind, double-dummy, parallel-group Phase IV study in patients who meet the International Classification of Headache Disorders criteria for a diagnosis of episodic migraine with or without aura. There will be two treatment arms: Emgality 120 mg once-monthly injection, with an initial 240 mg loading dose, and Nurtec ODT 75 mg, taken every other day. The study’s primary endpoint is 50 percent reduction in monthly migraine headache days. Enrollment is expected to begin during 2021.
In The Pipeline
In February, Lilly announced that tirzepatide led to significant A1C and body weight reductions from baseline in adults with type 2 diabetes in the SURPASS-3 and SURPASS-5 Phase III clinical trials after 52 weeks and 40 weeks, respectively. In topline results, the primary and all key secondary endpoints were met for both estimands in SURPASS-3, which compared tirzepatide to titrated insulin degludec, and in SURPASS-5, which compared tirzepatide to placebo, both as an add-on to titrated insulin glargine.
Using the efficacy estimand, the highest dose of tirzepatide (15 mg) reduced A1C by 2.37 percent and body weight by 12.9 kg (13.9 percent) in SURPASS-3, and reduced A1C by 2.59 percent and body weight by 10.9 kg (11.6 percent) in SURPASS-5. At the highest dose, 62.4 percent of SURPASS-5 participants – who had a mean duration of diabetes of 13.3 years – achieved an A1C of less than 5.7 percent, the level seen in people without diabetes.
In March, Lilly announced that mirikizumab met the primary and all key secondary endpoints in LUCENT-1, a 12-week Phase III induction study evaluating the efficacy and safety of mirikizumab for the treatment of patients with moderate to severe ulcerative colitis. In LUCENT-1, mirikizumab met the primary endpoint of clinical remission at Week 12 compared to placebo. Clinical remission is met when inflammation of the colon is controlled or resolved, leading to normalization or near-normalization of symptoms such as stool frequency and bleeding.
Also in March, Lilly presented from the Phase II TRAILBLAZER-ALZ trial finding that donanemab met its primary endpoint and showed significant slowing of decline on the integrated Alzheimer’s Disease Rating Scale, a composite measure of cognition and daily function, in patients with early symptomatic Alzheimer’s disease compared to placebo. Additionally, data from secondary analyses showed donanemab consistently slowed cognitive and functional decline, with ranges between 20-40 percent in all secondary endpoints with nominal statistical significance at multiple times compared to placebo. Further, prespecified exploratory analyses showed donanemab slowed the accumulation of tau across key brain regions in patients affected by Alzheimer’s disease.
That same month, Lilly announced that tirzepatide led to superior A1C and body weight reductions from baseline across all three doses compared to injectable semaglutide 1 mg in adults with type 2 diabetes in the SURPASS-2 clinical trial. In topline results, using the efficacy estimand, the highest dose of tirzepatide (15 mg) reduced A1C by 2.46 percent and body weight by 12.4 kg (27.3 lb., 13.1 percent). The lowest dose of tirzepatide (5 mg) reduced A1C by 2.09 percent and body weight by 7.8 kg (17.2 lb., 8.5 percent) compared to semaglutide at 1.86 percent and 6.2 kg (13.7 lb., 6.7 percent). Additionally, 51 percent of those taking tirzepatide 15 mg achieved an A1C of less than 5.7 percent – the level seen in people without diabetes, compared to 20 percent of those taking semaglutide.
In May, Lilly announced data from a pre-specified analysis of the Phase II SERENITY study showing that mirikizumab improved fatigue in patients with moderately to severely active Crohn’s disease at 12 weeks, as measured by the mean change in FACIT-Fatigue scores compared to placebo, with improvements that were sustained up to one year. In SERENITY, patients treated with mirikizumab saw improvements in fatigue during the induction period of 12 weeks, as measured by the mean change in FACIT-Fatigue scores from baseline compared to placebo.
That same month, FDA accepted for review a Biologics License Application for sintilimab injection in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer. This is the first U.S. regulatory submission of sintilimab, a PD-1 inhibitor being developed and commercialized under a global collaboration agreement between Innovent Biologics Inc. and Lilly.
Sintilimab is being evaluated in a wide variety of cancer types under a broad clinical development program. To date, sintilimab has two indications approved in China, three regulatory submissions under review in China, and this regulatory application under review in the United States. This regulatory application was primarily based on the results of the Phase III ORIENT-11 trial.
Also in May, Lilly announced that tirzepatide led to superior A1C and body weight reductions from baseline across all three doses in adults with type 2 diabetes who have increased cardiovascular risk compared to titrated insulin glargine in topline results from the SURPASS-4 clinical trial.
For the efficacy estimand, the highest dose of tirzepatide led to an A1C reduction of 2.58 percent and reduced body weight by 11.7 kg (25.8 lb., 13.0 percent) compared to results for those treated with insulin glargine (A1C reduction of 1.44 percent and weight gain of 1.9 kg [4.2 lb., 2.2 percent]) at 52 weeks.
In June, Lilly announced that tirzepatide led to superior A1C and body weight reductions from baseline across all three doses in adults with type 2 diabetes after 40 weeks of treatment in the SURPASS-1 monotherapy clinical trial evaluating the efficacy and safety of tirzepatide compared to placebo. Study participants in SURPASS-1, 54.2 percent of whom were treatment-naïve, had a relatively short mean duration of diabetes of 4.7 years, a baseline A1C of 7.9 percent, and a baseline weight of 85.9 kg. For the efficacy estimand, tirzepatide reduced A1C by up to 2.07 percent and body weight by up to 9.5 kg (20.9 lb., 11.0 percent) compared to placebo (+0.04 A1C change and body weight change of -0.7 kg [1.5 lb., 0.9 percent]). Up to 52 percent of participants achieved an A1C less than 5.7 percent – the level seen in people without diabetes. Tirzepatide also led to improvements in the change in fasting serum glucose from baseline. In an additional secondary endpoint, tirzepatide led to improvements in the change in two-hour post-meal glucose values from baseline from self-monitored blood glucose data.
That same month, Lilly announced that tirzepatide led to superior A1C and body weight reductions from baseline compared to injectable semaglutide 1 mg in 40-week results from the SURPASS-2 clinical trial. Additionally, a prespecified exploratory composite endpoint comprised of participants who achieved an A1C level less than or equal to 6.5 percent and weight loss of 10 percent or greater, while not experiencing hypoglycemia less than 54 mg/dL or severe hypoglycemia, was evaluated. Across the three doses of tirzepatide, 32 percent (5 mg), 51 percent (10 mg) and 60 percent (15 mg) of participants achieved this composite endpoint compared to 22 percent of participants taking semaglutide 1 mg.
In July, Lilly announced new Phase II data showing that gene expression changes induced by mirikizumab in patients with ulcerative colitis over a 12-week induction treatment were maintained for up to one year. These gene transcript changes, which were unique among those who responded to mirikizumab compared to placebo, were associated with mucosal healing, indicating that mirikizumab affects a distinct molecular healing pathway, compared to the spontaneous healing that occurred among those who responded to placebo.
In this analysis, a set of differentially expressed gene transcripts were identified in patients who responded to mirikizumab that were not found in those who responded to placebo at 12 weeks. Of the modulated genes, 71 percent were present only in patients who responded to mirikizumab, 5.6 percent were present only in those who responded to placebo, and 23.6 percent were present in both groups. Effect size estimates were also examined to account for differences in sample size and associated power between treatment groups. The set of gene transcripts regulated by mirikizumab correlated with UC disease activity indices, demonstrating consistency of these molecular changes across symptomatic, clinical, endoscopic and histologic indices of UC disease activity.
Also in July, Lilly presented two new analyses of data from the Phase II TRAILBLAZER-ALZ study. In the first, greater amyloid plaque changes following donanemab treatment was highly associated with less cognitive decline and participants with greater plaque clearance at 24 weeks of treatment showed less tau progression. In the second, Lilly shared data showing that treatment with donanemab drives a rapid reduction of a biomarker reflecting Alzheimer’s disease pathology, plasma P-tau217, which was detected within 12 weeks. FDA granted Breakthrough Therapy designation to donanemab during June.
In August, FDA approved an expanded label for the rapid-acting insulin Lyumjev (insulin lispro-aabc injection) 100 units/mL to improve glycemic control in adults with type 1 and type 2 diabetes, to include administration via continuous subcutaneous insulin infusion with an insulin pump. Lyumjev, a novel formulation of insulin lispro developed to speed the absorption of insulin into the bloodstream and reduce A1C levels, was approved by the FDA in June 2020.
The approval was based on results from PRONTO-PUMP-2, a Phase III treat-to-target study that confirmed the efficacy and safety of Lyumjev when used in insulin pumps in adults with type 1 diabetes. The study met the primary endpoint of noninferior A1C reduction from baseline to week 16 compared to Humalog. Lyumjev demonstrated superior reduction in blood glucose spikes at both one and two hours after a test meal compared to Humalog.
Also during August, Lilly announced that lebrikizumab led to significant improvements with at least 75 percent skin clearance in more than half of people with moderate-to-severe atopic dermatitis, in the ADvocate 1 and ADvocate 2 Phase III clinical trials. In the top-line results of lebrikizumab as a monotherapy in AD, primary and all key secondary endpoints, including skin clearance and itch improvement, were met at Week 16. Lebrikizumab is a novel monoclonal antibody that binds soluble IL-13 with high affinity and blocks IL-13 signaling. FDA has granted Fast Track designation to lebrikizumab for moderate-to-severe AD in adult and adolescent patients (aged 12 to less than 18 years of age and weighing at least 40 kg).