Eli Lilly 2020: Finally on top

Long known as a diabetes-focused company, Lilly now has the world’s leading diabetes brand in Trulicity.

By Joshua Slatko • [email protected]

Eli Lilly and Co.

Lilly Corporate Center
Indianapolis, IN 46285
Telephone: 317-276-2000
Website: lilly.com

 

FINANCIAL PERFORMANCE

(All figures are in millions of dollars, except EPS)

2019

Revenue $22,320 

Net income $8,318  

Diluted EPS $8.89  

R&D expense $5,595  

1H 2020

Revenue $11,359  

Net income $2,869 

Diluted EPS $3.15 

R&D expense $2,782  

 

BEST-SELLING Rx PRODUCTS

(All sales are in millions of dollars)

2019

Trulicity $4,128  

Humalog $2,821  

Alimta $2,116  

Forteo $1,405 

Taltz $1,366  

Humulin $1,290  

Basaglar $1,113  

Jardiance $944  

Cyramza $925  

Cialis $891

Cymbalta $725  

Trajenta $591  

Verzenio $580 

Erbitux $543  

1H 2020

Trulicity $2,459  

Humalog $1,251  

Alimta $1,099  

Taltz $839  

Humulin $629  

Basaglar $594  

Jardiance $530  

Forteo $525  

Cyramza $496 

Verzenio $397  

Cymbalta $390  

Cialis $324  

Olumiant $285  

Erbitux $260  

 

Outcomes Creativity Index Score: 79
Manny Awards – 7
Cannes Lions – N/A
LIA: Health & Wellness – 4
Clio Health – 20
One Show: HW&P – 2
MM&M Awards – 10
Global Awards – 16
Creative Floor Awards – 20

 

Eli Lilly and Co. has been known for diabetes treatments for much of its history. Nearly a century ago the company launched the first commercially available insulin product in the United States, and brands like Humalog and Humulin have been reliable revenue generators for many years. More recently, though, others have monopolized the top of the diabetes market, most notably Sanofi’s Lantus and Merck’s Januvia. But no longer. Helped along by a sales jump of nearly 30 percent, Lilly’s Trulicity took over as the world’s leading diabetes brand by sales in 2019, and the product looks likely to defend its crown in 2020. Meanwhile, another of Lilly’s type 2 diabetes products, Jardiance, enjoyed growth of more than 40 percent and looks to pass $1 billion in sales during 2020, and the long-acting human insulin analog Basaglar nearly matched that growth rate while passing the blockbuster mark in 2019. Products in other spaces, like the autoimmune brand Taltz and the oncologic Verzenio, are also showing impressive signs of future potential. All in all, good times for America’s diabetes company.

“Lilly is in the early phase of an exciting period of growth for the company,” said Chairman and CEO David Ricks on Jan. 30, 2020, in revealing the company’s 2019 financial results. “The combination of strong revenue growth from our newer medicines and prudent expense control across our business enabled Lilly to invest more in our R&D pipeline and still deliver impressive earnings growth in … 2019. We look forward to continuing this progress in 2020, as our scientists work to expand our portfolio of innovative medicines.”

Lilly’s top line in 2019 totaled $22.32 billion, an improvement of 3.8 percent over the previous year. Net income more than doubled, from $3.23 billion to $8.32 billion, with diluted earnings per share rising from $3.13 to $8.89. However, this increase was impacted significantly by a one-time $3.7 billion gain related to the disposition of Lilly’s stake in Elanco Animal Health in March 2019. On a continuing operations basis, Lilly’s net income in 2019 was $4.64 billion, still a 47.2 percent improvement, and EPS rose by $1.91 to $4.96. In the first half of 2020, Lilly’s top-line revenue rose 5.9 percent to $11.36 billion. Net income was down by nearly half to $2.87 billion, and EPS declined from $5.84 to $3.15. Again adjusting for the Elanco gain in the first half of 2019, net income from continuing operations in the first half of 2020 actually rose by 51.9 percent, and EPS was up by $1.17. Lilly executives projected full-year 2020 EPS to fall between $6.48 and $6.68. 

Partnerships & acquisitions

In January 2020, Lilly and Dermira Inc. announced a definitive agreement for Lilly to acquire Dermira for $18.75 per share, or about $1.1 billion, in an all-cash transaction. Dermira is a biopharmaceutical company dedicated to developing new therapies for chronic skin conditions. The transaction duly closed the following month.

The acquisition, company leaders say, expands Lilly’s immunology pipeline with the addition of lebrikizumab, a novel, investigational monoclonal antibody designed to bind IL-13 with high affinity. The new drug candidate is being evaluated in a Phase III clinical development program for the treatment of moderate-to-severe atopic dermatitis in adolescent and adult patients, ages 12 years and older. Lebrikizumab was granted Fast Track Designation from FDA in December 2019. The acquisition of Dermira also expanded Lilly’s portfolio of marketed dermatology medicines with the addition of Qbrexza, a medicated cloth approved by FDA for the topical treatment of primary axillary hyperhidrosis (uncontrolled excessive underarm sweating).

During March, Lilly announced an exclusive global licensing and research collaboration with Sitryx, a biopharmaceutical company focused on regulating cell metabolism to develop disease-modifying therapeutics in immuno-oncology and immuno-inflammation. The collaboration will study up to four novel preclinical targets identified by Sitryx that could lead to potential new medicines for autoimmune diseases.

Under the terms of the agreement, Sitryx received an upfront payment of $50 million and Lilly will make a $10 million equity investment in Sitryx. Sitryx will be eligible to receive potential development milestones up to $820 million, as well as commercialization milestones and royalty payments on potential sales in the mid- to high-single digit range. In return, Sitryx granted Lilly an exclusive, worldwide license to develop and commercialize up to four novel immunometabolism targeted therapeutics, including Sitryx’s two lead projects. Lilly and Sitryx established a five-year research collaboration to support the development of the therapeutics, with Sitryx responsible for drug discovery, while Lilly is funding and manage the clinical development and commercial phase of the collaboration.

In August, Lilly and Innovent Biologics Inc. announced a global expansion of their strategic alliance for Tyvyt (sintilimab injection), an anti-PD-1 monoclonal antibody immuno-oncology medicine that was co-developed by Innovent and Lilly in China.

In 2019, Lilly and Innovent began commercializing Tyvyt in China after being granted marketing approval for relapsed or refractory classic Hodgkin’s lymphoma after at least two lines of systemic chemotherapy. Tyvyt is the only PD-1 inhibitor to be included in China’s National Reimbursement Drug List and is included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies.

Lilly and Innovent co-commercialize Tyvyt in China. Under the terms of the expanded license agreement, Lilly obtained an exclusive license for Tyvyt for geographies outside of China and plans to pursue registration of Tyvyt in the United States and other markets. Both companies also retain the right to study Tyvyt in combination with other medicines as part of their own clinical programs.

The two companies are also studying Tyvyt as a potential therapy in non-squamous non-small cell lung cancer and several other types of cancer. Additionally in August, the two companies released encouraging interim analysis data from ORIENT-11, a randomized, double-blind Phase III clinical trial evaluating Tyvyt or placebo in combination with Alimta and platinum chemotherapy as a first-line treatment for advanced or recurrent non-squamous NSCLC without sensitizing EGFR mutations or ALK rearrangements. Based on the interim analysis conducted by the Independent Data Monitoring Committee, Tyvyt in combination with Alimta and platinum chemotherapy demonstrated a statistically significant improvement in progression-free survival compared with placebo in combination with Alimta and platinum chemotherapy, which met the pre-defined efficacy criteria. A supplemental new drug application for this indication is under regulatory review in China. The companies look forward to future submissions with FDA and other regulatory agencies for this and other indications.

Product performances

The type 2 diabetes product Trulicity solidified its position atop Lilly’s portfolio in 2019 with a sales jump of 29 percent to $4.13 billion. According to company leaders, this result was due to higher demand in the United States and increased volume internationally, where the product enjoyed a 42 percent increase in sales. Trulicity has continued its upward trajectory in 2020, with sales rising another 28.9 percent to $2.46 billion. 

In February, FDA approved Trulicity for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. This made Trulicity the first type 2 diabetes medicine approved to reduce the risk of MACE for both primary and secondary prevention populations.

The new indication reflects the differentiated patient population of REWIND, the Trulicity cardiovascular outcomes trial. While all participants had CV risk factors, the study consisted primarily of people without established CV disease. REWIND showed a significant risk reduction in MACE, a composite endpoint of nonfatal myocardial infarction (heart attack), nonfatal stroke, or CV death. Results demonstrated consistent MACE risk reduction with Trulicity across major demographic and disease subgroups. Trulicity’s safety profile was consistent with the GLP-1 receptor agonist class. 

In June, Lilly announced new real-world data showing that Trulicity had significantly higher adherence and longer persistence compared to weekly injections of semaglutide or exenatide (BCise pen) in people with type 2 diabetes new to GLP-1 receptor agonist treatment.

At six months, people taking Trulicity showed higher adherence and persistence than those taking semaglutide or exenatide. Further, significantly fewer people discontinued treatment with Trulicity compared to semaglutide or exenatide. In the comparison between Trulicity and injectable semaglutide, Trulicity had adherence of 59.7 percent versus semaglutide’s 42.7 percent, persistence of 143.6 days compared with semaglutide’s 129.9 days, and treatment discontinuation of 30.8 percent compared with 40.8 percent for semaglutide. In the comparison between Trulicity and exenatide, Trulicity had adherence of 58.1 percent versus 40.3 percent for exenatide, persistence of 142 days compared with 121.4 days for exenatide, and treatment discontinuation of 32.1 percent versus 49.4 percent for exenatide. 

In September, FDA expanded the label of once-weekly Trulicity to include 3.0 milligram and 4.5 milligram doses based on data from AWARD-11. The Phase III trial showed the additional doses led to further benefits in A1C and body weight reduction when compared to Trulicity 1.5 milligram in people with type 2 diabetes.

The AWARD-11 trial evaluated the safety and efficacy of additional doses of Trulicity (3.0 milligrams and 4.5 milligrams) compared to Trulicity 1.5 milligrams, using two different statistical approaches. The efficacy estimand, which analyzes participants who remained on treatment throughout the trial, showed both doses led to significant reductions in A1C and weight. The 4.5 milligram dose led to a 1.9 percent reduction in A1C and a 10.4 pound reduction in weight, while the 3.0 milligram dose led to a 1.7 percent reduction in A1C and an 8.8 pound reduction in weight. These both compared favorably to the 1.5 milligram dose, which led to a 1.5 percent reduction in A1C and a 6.8 pound reduction in weight.

Sales of the injectable human insulin analog Humalog began to decline in 2019, falling 5.8 percent to $2.82 billion. This performance was not unexpected given the launch of a similar version of insulin lispro in Europe in 2017 and the United States in the second quarter of 2018. In the first half of 2020, Humalog sales fell by another 11.2 percent to $1.25 billion.

In April, Lilly announced that non-branded versions of Humalog Mix75/25 KwikPen and Humalog Junior KwikPen were made available for order by U.S. pharmacies. These non-branded insulin options are identical to the branded versions, with different packaging and a 50 percent lower list price of $265.20 for a package of five KwikPens.

This new availability followed the launch of the Lilly Insulin Value Program, which reduces the monthly prescription out-of-pocket cost for most Lilly insulins to $35 for people with commercial insurance and those with no insurance. Both of these non-branded options are eligible for the $35 co-pay program.

The oncologic Alimta generated sales of $2.12 billion for Lilly in 2019, a decline of 0.8 percent. According to company leaders, this was a tale of two territories; in the United States Alimta sales rose by 8 percent due to increased demand, while ex-U.S. sales declined by 11 percent due to lower realized prices and the entry of generic competition in Germany. A generic competitor to Alimta in the United States is expected to launch in February 2022. Alimta sales in the first half of 2020 were $1.2 billion, an improvement of 2 percent. 

Forteo, for patients with osteoporosis at high risk of fracture, brought in $1.41 billion in sales for Lilly in 2019, a decline of 10.9 percent. According to company leaders, this was due to decreased U.S. demand and decreased international volume. In the first half of 2020, sales of Forteo declined 22.1 percent to $525 million. Lilly executives are expecting further declines due to the market entry of generic and biosimilar competition to Forteo in the third quarter of 2019. 

The autoimmune product Taltz was one of the more impressive performers in Lilly’s portfolio in 2019, enjoying a sales bounce of 45.6 percent to $1.37 billion. Ex-U.S. growth was particularly strong, with sales rising 76 percent internationally due to increased volume from recent launches. In the first half of 2020 sales of Taltz rose another 38.4 percent to $839 million. 

In March, FDA approved a supplemental biologics license application for Taltz injection, 80 mg/mL for the treatment of pediatric patients (ages 6 to under 18) with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Psoriasis affects nearly 8 million people in the U.S. Many people living with psoriasis develop symptoms during childhood.

The safety, tolerability and efficacy of Taltz in patients ages 6 to under 18 years old was demonstrated in a randomized, double-blind, placebo-controlled Phase III study that included 171 patients with moderate to severe plaque psoriasis. The co-primary endpoints of the study were the proportion of patients achieving a 75 percent improvement from baseline on their Psoriasis Area and Severity Index score (PASI 75) and a static Physician’s Global Assessment of clear or almost clear skin (sPGA 0,1) at Week 12.

Patients were randomized to receive Taltz (20 milligrams for <25 kg, 40 milligrams for 25-50 kg or 80 milligrams for >50 kg through Week 12, with 40 milligram, 80 milligram, or 160 milligram starting doses, respectively) or placebo. At 12 weeks, the proportion of patients achieving the co-primary endpoints was superior to placebo with statistically significant difference. 89 percent of patients treated with Taltz achieved PASI 75 compared to 25 percent of patients treated with placebo, and 81 percent of patients treated with Taltz achieved sPGA 0,1 compared to 11 percent of patients treated with placebo.

In June, Lilly announced new data showing that Taltz demonstrated consistent efficacy and long-term potential to help patients with psoriatic arthritis. The new results came from a subgroup analysis of the Phase IIIb/IV, 52-week SPIRIT-Head-to-Head (SPIRIT-H2H) study of Taltz versus Humira in biologic-naïve patients with active psoriatic arthritis. SPIRIT-H2H was the first superiority study versus Humira in PsA with a primary endpoint of simultaneous achievement of ACR50 (at least 50 percent improvement in disease activity as defined by the American College of Rheumatology) and PASI 100 (100 percent improvement in the Psoriasis Area and Severity Index) at Week 24. 

In this prespecified analysis, efficacy outcomes through Week 52 were compared between Taltz and Humira in subgroups of patients on monotherapy, concomitant methotrexate, or concomitant MTX along with an additional conventional synthetic disease-modifying antirheumatic drug (csDMARD), including sulfasalazine, cyclosporine, or leflunomide. Results at 52 weeks showed improvements were seen with Taltz across multiple endpoints, with or without the use of MTX or other csDMARDs.

A higher proportion of patients treated with Taltz achieved Minimal Disease Activity (MDA) compared to Humira in the monotherapy subgroup (49 percent versus 33 percent), while response rates were similar between Taltz and Humira in the concomitant MTX subgroup (47 percent versus 47 percent) and concomitant csDMARD subgroup (47 percent versus 44 percent). MDA is an endpoint that includes fulfilling at least five of seven rheumatology outcome measures and is the treatment target according to multiple professional organizations.

More Taltz patients achieved the primary endpoint of simultaneous achievement of ACR50 and PASI 100 at Week 52 in all three subgroups: monotherapy (Taltz 38 percent, Humira 19 percent), concomitant MTX (Taltz 39 percent, Humira 30 percent), and concomitant csDMARDS (Taltz 40 percent, Humira 29 percent).

A greater proportion of patients treated with Taltz versus Humira achieved PASI 100 when used as monotherapy (66 percent vs 35 percent), in combination with MTX (63 percent versus 44 percent), or in combination with csDMARDs (64 percent versus 44 percent) and the proportion of patients achieving ACR50 was comparable between Taltz and Humira, regardless of monotherapy (51 percent versus 42 percent), concomitant MTX (48 percent versus 56 percent), or concomitant csDMARD use (49 percent versus 53 percent).

Also in June, FDA approved a supplemental biologics license application for Taltz injection 80 mg/mL for the treatment of active non-radiographic axial spondyloarthritis in patients with objective signs of inflammation. Another first-in-class milestone for the treatment, this approval makes Taltz the first IL-17A antagonist to be approved by the FDA for nr-axSpA.

This approval was based on the results from the Phase III COAST-X trial, which evaluated improvement in signs and symptoms of nr-axSpA as measured by the proportion of patients who achieved Assessment of Spondyloarthritis International Society 40 (ASAS40) response criteria compared to placebo. ASAS40 measures disease signs and symptoms such as pain, inflammation and function.

The injectable human insulin Humulin generated $1.29 billion in sales for Lilly in 2019, down 3.1 percent compared with the previous year. This was driven by lower realized prices in the United States and unfavorable impact of exchange rates elsewhere. In the first half of 2020 Humulin sales edged up by 1.5 percent to $629 million.

The long-acting human insulin analog Basaglar passed the blockbuster barrier in 2019 with sales of $1.11 billion, an improvement of 39 percent over 2018. This was pushed along by higher realized prices and increased demand in the United States and increased volume internationally. In the first half of 2020, sales of Basaglar rose another 9.6 percent to $594 million.

Jardiance, for type 2 diabetes and reducing the risk of cardiovascular death in adult patients with type 2 diabetes and established cardiovascular disease, approached blockbuster status in 2019, with sales rising 43.5 percent to $944 million. According to company leaders, this was due to increased demand in the United States and volume growth internationally. In the first half of 2020, sales of Jardiance were up another 21.6 percent to $530 million.

In March, FDA granted Fast Track designation for the investigation of Jardiance to reduce the risk of kidney disease progression and cardiovascular death in adults with chronic kidney disease. This Fast Track designation for Jardiance underscores the urgent need for additional treatment options for the more than 30 million Americans living with chronic kidney disease, many of whom are at risk of progressing to end-stage kidney disease.

The ongoing EMPA-KIDNEY clinical study is evaluating the effect of Jardiance on the progression of kidney disease and occurrence of cardiovascular death in adults with established chronic kidney disease with and without diabetes. The study was initiated based on promising exploratory results from the landmark EMPA-REG OUTCOME trial, which found that treatment with Jardiance reduced the risk of new-onset and worsening kidney disease by 39 percent in adults with type 2 diabetes and established cardiovascular disease compared with placebo.

Also in March, FDA issued a complete response letter for the supplemental New Drug Application of empagliflozin 2.5 milligrams as an adjunct to insulin for adults with type 1 diabetes. Empagliflozin 2.5 milligrams is being developed by Boehringer Ingelheim and Lilly. The letter indicated that FDA is unable to approve the application in its current form, consistent with the outcome of the Endocrinologic and Metabolic Drugs Advisory Committee in November 2019.

In August, Lilly announced full results from the EMPEROR-Reduced Phase III trial in adults with heart failure with reduced ejection fraction, with and without diabetes, showing that Jardiance was associated with a significant 25 percent relative risk reduction in the primary endpoint of time to cardiovascular death or hospitalization due to heart failure. The trial evaluated the effect of adding Jardiance (10 milligrams) versus placebo to standard of care.

The findings from the primary endpoint were consistent in subgroups with and without type 2 diabetes. Key secondary endpoint analyses from the trial demonstrated that Jardiance reduced the relative risk of first and recurrent hospitalization for heart failure by 30 percent. Additionally, the rate of decline in eGFR, a measure of kidney function decline, was slower with Jardiance than with placebo.

In an exploratory analysis, the absolute risk reduction observed in the primary endpoint of EMPEROR-Reduced corresponded to a number needed to treat of 19 patients over 16 months to prevent one cardiovascular death or hospitalization for heart failure. An additional exploratory analysis showed that Jardiance decreased the relative risk of a composite kidney endpoint, including end-stage kidney disease and a profound loss of kidney function, by 50 percent.

The oncologic Cyramza also approached blockbuster status for Lilly in 2019, with sales up by 12.7 percent to $925 million. Lilly executives say this was due to increased demand and higher realized prices in the United States and increased volume internationally. In the first half of 2020, Cyramza sales rose 12.7 percent to $496 million.

FDA approved Cyramza in May in combination with erlotinib for the first-line treatment of people with metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations. Cyramza plus erlotinib is the first FDA-approved anti-VEGFR/EGFR TKI combination therapy for metastatic EGFR-mutated NSCLC. 

This approval was based on the efficacy and safety from the global, randomized, placebo-controlled Phase III RELAY trial. In this trial, Cyramza in combination with erlotinib, a globally approved EGFR-targeting tyrosine kinase inhibitor, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared to placebo in combination with erlotinib (19.4 months in the Cyramza arm versus 12.4 months in the placebo-containing arm). The PFS treatment effect was consistent across exon 19 and exon 21 subgroups. RELAY is the second positive Phase III trial of Cyramza in metastatic NSCLC. The first was REVEL, which supported the approval of Cyramza plus docetaxel as a treatment for people with metastatic NSCLC whose cancer has progressed after prior platinum-based chemotherapy.

The breast cancer drug Verzenio more than doubled its sales in 2019, from $255 million to $580 million. In the first half of 2020, sales of Verzenio rose 63.4 percent to $398 million. According to company leaders, this was due to increased demand and higher realized prices. 

In June, Lilly announced that Verzenio in combination with standard adjuvant endocrine therapy had met the primary endpoint of invasive disease-free survival, significantly decreasing the risk of breast cancer recurrence or death compared to standard adjuvant ET alone. These results were from a pre-planned interim analysis of the Phase III monarchE study – making Verzenio the only CDK4 and 6 inhibitor to demonstrate a statistically significant reduction in the risk of cancer recurrence for people with high risk hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer.

In the pipeline

Lilly and Incyte announced in January that baricitinib met the primary endpoint in BREEZE-AD4. The investigational Phase III, randomized, placebo-controlled study is evaluating the safety and efficacy of baricitinib with topical corticosteroids for the treatment of adult patients with moderate to severe atopic dermatitis who were inadequate responders, intolerant or had contraindication to treatment with cyclosporine. The primary endpoint was defined by the proportion of patients achieving at least a 75 percent or greater change from baseline in their Eczema Area and Severity Index at Week 16.

BREEZE-AD4 is a multicenter, double-blind, randomized, placebo-controlled study conducted outside of the United States. The study evaluated the efficacy and safety of the 1-milligram, 2-milligram, and 4-milligram doses of baricitinib in combination with TCS in patients with moderate to severe AD who have experienced failure to cyclosporine or are intolerant to – or have contraindication to – cyclosporine. In this study, the 4-mg dose of baricitinib plus TCS met the primary endpoint as defined by the proportion of participants achieving EASI75 at Week 16.

In February, Lilly announced that Reyvow (lasmiditan), an oral medication for the acute treatment of migraine with or without aura in adults, was available for prescription and would be available in pharmacies within a few days. Reyvow represents a new class of acute treatment for migraine as the first FDA-approved ditan, a 5-HT1F receptor agonist, believed to act both centrally and peripherally.

The efficacy of Reyvow for the acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled, single-attack trials of 4,439 patients who took 50-milligram, 100-milligram, or 200-milligram doses of Reyvow or placebo. Pain freedom, defined as a reduction of moderate or severe headache pain to no pain at two hours, and freedom from MBS, defined as the absence of the self-identified MBS (photophobia, phonophobia, or nausea) at two hours, were the primary and secondary efficacy endpoints. Across two clinical studies and three doses, 28-39 percent of patients achieved complete elimination of migraine pain at two hours with Reyvow compared to 15 percent and 21 percent with placebo. Across two clinical studies and three doses, 41-49 percent of patients achieved freedom from their MBS at two hours with Reyvow versus 30 percent and 33 percent with placebo.

In March, FDA granted Breakthrough Therapy designation to baricitinib for the treatment of alopecia areata, an autoimmune disorder that can cause unpredictable hair loss on the scalp, face and other areas of the body. The Breakthrough Therapy designation aims to expedite the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over already available therapies on a clinically significant endpoint(s). 

The FDA Breakthrough Therapy designation is based on the positive Phase II results of Lilly’s adaptive Phase II/III study BRAVE-AA1, which evaluated treatment with baricitinib versus placebo in adult patients with AA. Based on the interim results of the Phase II part of the study, the Phase III portion of BRAVE-AA1 and an additional Phase III double-blind study (BRAVE-AA2) are assessing the efficacy and safety of the 2-milligram and 4-milligram doses of baricitinib relative to placebo.

In other March highlights, FDA accepted for review a biologics license application for tanezumab 2.5 milligrams administered subcutaneously, which is being evaluated for patients with chronic pain due to moderate-to-severe osteoarthritis who have experienced inadequate pain relief with other analgesics. The tanezumab regulatory submission encompasses data from 39 Phase I-III clinical studies evaluating the safety and efficacy of tanezumab among more than 18,000 patients, including three Phase III studies evaluating SC administration of tanezumab in patients with moderate-to-severe OA.

In May, Lilly announced that Emgality significantly improved work productivity and reduced interictal burden, defined as health and well-being between migraine attacks, in an analysis of the 3-month double-blind period of the CONQUER study, which included patients with migraine from 12 different countries. 

Among the 462 patients randomized to Emgality or placebo, there were statistically significant improvements in work productivity and reductions in overall work productivity loss for the Emgality group compared with placebo (-14.3 percent versus -3.5 percent). These gains in productivity appeared to be driven by statistically significant improvements in presenteeism (-12.5 percent versus -2.6 percent). Absenteeism was low and not significantly different between groups. Non-work-related activity impairment was statistically significantly reduced in the Emgality group compared to placebo (-20.7 percent versus -8.6 percent). Results were similar in the subgroups of patients with episodic or chronic migraine.

Also in May, FDA approved Retevmo (selpercatinib), the first therapy specifically indicated for the treatment of adult patients with metastatic rearranged during transfection fusion-positive non-small cell lung cancer, and the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Retevmo was approved under FDA’s Accelerated Approval regulations based on the LIBRETTO-001 Phase I/II trial’s endpoints of objective response rate and duration of response.

The single-arm, multi-center Phase I/II LIBRETTO-001 trial was the largest trial of patients with RET-driven cancers. The trial enrolled both treatment-naive patients and heavily pretreated patients with a variety of advanced solid tumors including RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and certain other solid tumors with RET alterations. Major efficacy outcomes were ORR and DoR, assessed by a blinded independent review committee. Prespecified secondary endpoints included central nervous system ORR and CNS DoR. Up to 50 percent of patients with RET fusion-positive NSCLCs can have tumors that metastasize to the brain. Among previously treated NSCLC patients with measurable brain metastases, 10 out of 11 patients observed intracranial responses (CNS ORR), with all 10 patients experiencing a CNS DoR of greater than or equal to six months.

In June, Lilly announced study results showing that Emgality reduced total pain burden in an analysis of patients with episodic and chronic migraine. Total pain burden is a patient-centric measure that combines the monthly frequency, duration and pain severity of migraine. Additionally, total pain burden demonstrated significant associations with patient functioning and quality of life. Emgality is the first migraine preventive CGRP medication to be assessed in this manner, providing a more complete picture of how the product reduced frequency, duration and severity.

This post hoc analysis of Emgality versus placebo used data from three randomized, double-blind studies in patients with episodic migraine and chronic migraine. Patients reported their headache frequency, duration, and severity using an electronic diary. Monthly total pain burden was calculated as severity-weighted duration by multiplying hours of migraine recorded and pain severity (0=none, 1=mild, 2=moderate, 3=severe) for each migraine day and summing these composite measurements over the migraine days in a month. In episodic migraine, patients on Emgality experienced 68.6 fewer severity-weighted hours of pain per month on average than at baseline and compared to those on placebo who experienced 36.2 fewer hours (mean difference = 32.3 fewer hours). In chronic migraine, patients on Emgality experienced 102.6 fewer severity-weighted hours of pain per month on average than at baseline and compared to those on placebo who experienced 44.4 fewer hours of pain than at baseline (mean difference = 58.2 severity-weighted hours).

Also in June, Lilly announced that the first patient had been enrolled in a Phase III randomized, double-blind, placebo–controlled study to evaluate the efficacy and safety of baricitinib in hospitalized adults with COVID-19. Baricitinib, branded as Olumiant, is approved in 70 countries for adults with moderately to severely active rheumatoid arthritis. Lilly expects to enroll 400 patients in the trial, with data anticipated during 2020. The study is being conducted in the United States, Europe, and Latin America and includes patients hospitalized with SARS-CoV-2 infection who have at least one elevated marker of inflammation but do not require invasive mechanical ventilation at study entry.

In COVID-19 infection, increased disease severity can be associated with a hyperinflammatory state. It is hypothesized that through JAK1 and JAK2 inhibition, baricitinib may reduce the cytokine storm associated with the complications of this infection. In addition, baricitinib may have a role in inhibiting the host cell proteins that assist in viral reproduction, reducing the ability of infected cells to make more virus.

Also in June, Lilly and its subsidiary Dermira presented new data from the Phase IIb clinical trial of lebrikizumab in patients with moderate-to-severe atopic dermatitis. Data from this study suggests that treatment with lebrikizumab provided rapid and clinically meaningful improvements in itch, sleep and overall measures of quality of life.

The results of the data analysis showed that lebrikizumab improved symptoms and quality of life in a rapid, dose-dependent manner across a range of atopic dermatitis-specific and other measures compared with placebo. Specifically, lebrikizumab improved itch by Day 2 with further improvement to Week 16; sleep by the first on-treatment assessment at Week 1 with further improvement to Week 16; and disease severity as assessed by the POEM (Patient-Oriented Eczema Measure) by the first on-treatment assessment at Week 16. Lebrikizumab also improved dermatology health-related quality of life scores by the first on-treatment assessment at Week 8; and patient global assessment of change at Week 16, with statistically significant improvements in patients treated with 250 milligrams Q4W or 250 milligrams Q2W of lebrikizumab, respectively, rating their atopic dermatitis as “1, much better” compared with patients treated with placebo.

Also in June, the first patient dose was delivered in SURPASS-CVOT, the Phase III cardiovascular outcomes trial for tirzepatide, Lilly’s investigational dual GIP and GLP-1 receptor agonist. The study is assessing both non-inferiority and superiority of tirzepatide in a head-to-head trial against Trulicity 1.5 milligrams, the market leading GLP-1 receptor agonist.

SURPASS-CVOT includes 12,500 participants with type 2 diabetes and atherosclerotic cardiovascular disease from 30 countries. The primary endpoint measures time to first occurrence of MACE-3, the composite endpoint of CV death, myocardial infarction or stroke. Key secondary endpoints measure time to all-cause mortality and time to occurrence of each component of the primary endpoint. Lilly anticipates the trial will take just over four years to complete.

Also in June, Lilly announced that its partner Junshi Biosciences had dosed the first healthy volunteer in a study of a potential neutralizing antibody treatment designed to fight COVID-19.

The investigational medicine, referred to as JS016, is being co-developed by Junshi Biosciences and Lilly. Junshi is leading development in Greater China. Lilly has exclusive rights in the rest of the world and began dosing patients in a complementary Phase I study in the United States shortly afterward. Both Phase I studies aim to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of JS016 in healthy participants who have not been diagnosed with COVID-19. 

In July, Lilly announced that mirikizumab met the primary and all key secondary endpoints versus placebo at Week 16 and all key secondary endpoints versus Cosentyx at Week 16 and Week 52 in the OASIS-2 study. OASIS-2 is a multicenter randomized, double-blind, placebo-controlled study comparing the efficacy and safety of mirikizumab to placebo and Cosentyx in patients with moderate to severe plaque psoriasis.

In OASIS-2, the primary endpoints were the proportion of patients with a Static Physician’s Global Assessment of (0,1) with at least a 2-point improvement and the proportion of patients with at least a 90 percent improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at Week 16 compared to placebo. Similar endpoints were evaluated at Week 16 as key secondary endpoints compared to Cosentyx. Other key secondary endpoints compared to placebo at Week 16 include the proportion of patients with at least a 75 and 100 percent improvement from baseline in Psoriasis Area and Severity Index (PASI 75/PASI 100).

Also in July, a new study on Lilly’s blood test for Alzheimer’s disease, P-tau217 (phosphorylated tau at threonine-217), was published in JAMA showing that P-tau217 distinguished AD from other neurodegenerative diseases significantly better than other blood-based biomarkers or magnetic resonance imaging. 

The cross-sectional three-cohort study included patients from an Arizona-based neuropathology cohort, the Swedish BioFINDER-2 cohort, and a cohort of Colombian autosomal-dominant AD relatives. The findings showed that P-tau217 accurately identified AD from other neurodegenerative diseases in both an Arizona-based neuropathology cohort and in the Swedish BioFINDER-2 study. In the third Colombian cohort, P-tau217 in mutation carriers’ blood was elevated about 20 years before anticipated symptom onset and was associated with memory performance.

In August, Lilly announced the initiation of BLAZE-2, a Phase III trial studying LY-CoV555 for the prevention of SARS-CoV-2 infection and COVID-19 in residents and staff at long-term care facilities in the United States (skilled nursing facilities, commonly referred to as nursing homes, and assisted living facilities). LY-CoV555, the lead antibody from Lilly’s collaboration with AbCellera, is a neutralizing antibody against SARS-CoV-2, the virus that causes COVID-19. The rapid spread of SARS-CoV-2 among residents of long-term care facilities combined with the higher mortality rate for the elderly creates the urgent need for therapies to prevent COVID-19 in this vulnerable population.

To address the challenging aspects of running a clinical trial in a long-term care facility during a pandemic, Lilly created customized mobile research units to support the on-site study. These units include a custom retrofitted recreational vehicle to support mobile labs and clinical trial material preparation, along with a trailer truck that will deliver all clinical trial supplies needed to create an on-site infusion clinic. To further minimize the burden on these facilities that normally do not conduct clinical trials, additional staff will be at the facilities to assist with the operations of the study. Lilly will deploy its mobile research unit fleet in response to outbreaks of the virus at long-term care facilities across the United States.

In September, Lilly announced data showing that adults who took Reyvow C-V for their migraine attacks at doses of 100 milligrams or 200 milligrams had 3.8 and 4.6 times greater odds, respectively, of achieving pain freedom at 2 hours compared to those taking placebo (co-primary endpoint), according to results from the recently completed Phase III study CENTURION. Additionally, Reyvow demonstrated superiority over placebo in all gated endpoints, including proportions of study participants who after treating their first migraine attack reported pain freedom at 1 hour (200 milligram dose), pain relief at 1 hour and 2 hours (both doses), sustained pain freedom at 24 hours (both doses) and 48 hours (200 mg dose), and no disability at 2 hours (both doses).

Study results showed that people receiving Reyvow 200 milligrams had 4.6 times greater odds of achieving pain freedom at 2 hours (co-primary endpoint) than those on placebo (29.3 percent versus 8.4 percent), with a therapeutic gain of about 21 percent. Study participants taking Reyvow 100 milligrams had 3.8 times greater odds of achieving pain freedom at 2 hours than those on placebo (25.8 percent versus 8.4 percent), with a therapeutic gain of about 17 percent. At 60 minutes, people who took Reyvow 200 milligrams had 7 times greater odds of achieving pain freedom than those on placebo (12.7 percent vs. 2.0 percent). Although not a gated endpoint, 6.0 percent of people receiving Reyvow 100 milligrams were pain-free at 1 hour vs. 2.0 percent on placebo.