AbbVie 2020: Beyond Humira

While the world’s leading prescription drug still generated more than half of AbbVie’s revenue in 2019, the acquisition of Allergan showed that company leaders are looking to what’s next.

By Joshua Slatko • [email protected]

 

 

 

AbbVie Inc.
1 North Waukegan Road
North Chicago, IL 60064
Telephone: 847-932-7900
Website: abbvie.com

 

Financial Performance

	2019	2018
Revenue	$33,266	$32,753
Net income	$7,882	$5,687
Diluted EPS	$5.28	$3.66
R&D expense	$6,407	$10,329

	1H 2020	1H 2019
Revenue	$19,044	$16,083
Net income	$2,271	$3,197
Diluted EPS	$1.43	$2.14
R&D expense	$2,961	$2,580

All figures are in millions of dollars, except EPS.

 

Best-Selling Rx Products

Product	2019 Sales	2018 Sales
Humira	$19,169	$19,936
Imbruvica	$4,674	$3,590
Mavyret	$2,893	$3,438
Creon	$1,041	$928
Lupron	$887	$892
Venclexta	$792	$344
Synthroid	$786	$776
Synagis	$718	$726

Product	1H 2020 Sales	1H 2019 Sales
Humira	$9,540	$9,316
Imbruvica	$2,520	$2,121
Mavyret	$935	$1,570
Skyrizi	$630	$48
Venclexta	$620	$320
Creon	$528	$484
Lupron	$438	$438
Synthroid	$388	$385
Botox Therapeutic	$297*	N/A

All sales are in millions of dollars.

* – Botox was acquired in the Allergan transaction; amount is from May 8 through June 30, 2020. 

 

Outcomes Creativity Index Score: 23
Manny Awards – N/A
Cannes Lions – N/A
LIA: Health & Wellness – N/A
Clio Health – 2
One Show: HW&P – N/A
MM&M Awards –11
Global Awards – 6
Creative Floor Awards – 4

 

Since the company’s birth as a spin-off from legacy Abbott Laboratories in 2013, the story of AbbVie has largely been the story of Humira. The 900-pound autoimmune gorilla has led the world in prescription drug sales every year since, up to and including – by a margin of more than $8 billion – 2019, while consistently accounting for well over half of AbbVie’s top-line revenue. At no time in recent history has any other major pharma company depended so much on the fate of a single product.

And in 2019, product sales began to decline. It wasn’t much, less than 4 percent, but Humira’s annual sales went down for the first time since the medicine was launched by Abbott in 2003. But the cause of the decline, international biosimilar competition, is not going away, which meant that looking beyond the horizon has become a matter of more than usual priority for AbbVie. The company’s most notable response, announced in June 2019 and completed this past May, was the $63 billion acquisition of Allergan.

“This is a transformational transaction for both companies and achieves unique and complementary strategic objectives,” said AbbVie chairman and CEO Richard A. Gonzalez when the deal was first announced in June 2019. “The combination of AbbVie and Allergan increases our ability to continue to deliver on our mission to patients and shareholders. With our enhanced growth platform to fuel industry-leading growth, this strategy allows us to diversify AbbVie’s business while sustaining our focus on innovative science and the advancement of our industry-leading pipeline well into the future.”

AbbVie’s top-line revenue in 2019 rose by 1.6 percent to $33.27 billion, while net income was up 38.6 percent to $7.88 billion and diluted earnings per share were up by $1.62 to $5.28. Helped along by nearly two months of legacy Allergan revenue, AbbVie’s top line in the first half of 2020 rose by 18.4 percent to $19.04 billion. Net income, though, declined 29 percent to $2.27 billion and diluted EPS was down 71 cents to $1.43. Company executives are projecting that full-year 2020 EPS will fall between $4.12 and $4.22. 

Allergan acquisition complete

In May, AbbVie completed the acquisition of Allergan plc following receipt of regulatory approval from all government authorities required by the transaction agreement and approval by the Irish High Court.

“We are pleased to reach this important milestone for the company, its employees, shareholders and the patients we serve,” Gonzalez said on completion of the acquisition. “Our new Allergan colleagues should be commended for all their efforts, along with those of our own employees, to achieve this turning point for our company. The new AbbVie will be a well-diversified leader in many important therapeutic categories, with both on-market and pipeline assets, and our financial strength will allow us to continue to invest in innovative science and continue to serve unmet medical needs of patients that rely upon us. I am proud of both organizations and look forward to the opportunities ahead.”

According to company executives, the transaction significantly expands and diversifies AbbVie’s revenue base. The acquisition also complements existing leadership positions in Immunology, with Humira and recently launched Skyrizi and Rinvoq, and Hematologic Oncology, with Imbruvica and Venclexta. Allergan provides new growth opportunities in Neuroscience, with Botox Therapeutic, Vraylar and Ubrelvy, and a global aesthetics business, with leading brands including Botox Cosmetic and Juvederm. 

This diversified on-market portfolio, company leaders say, will drive the existing AbbVie growth platform (ex-Humira) to about $30 billion in revenue in full-year 2020, with combined revenue of about $50 billion. The transaction also positions the company for enhanced long-term growth potential, a growing dividend, and investment in innovation in each of its therapeutic categories. Company leaders anticipate rapidly paying down the incremental debt with increased operating cash flows.

Four months before the completion of the acquisition, AbbVie announced the creation of a new global business – Allergan Aesthetics, an AbbVie company – and the proposed leadership team for the combined company, effective on close. 

Allergan Aesthetics operates as a new global dedicated business with its own research and development function under the AbbVie umbrella and includes leading aesthetic products such as Botox Cosmetic, the Juvederm collection of dermal fillers, and Coolsculpting body contouring, among others. This global business, located in Irvine, Calif., is led by Carrie Strom, previously senior VP, U.S. Medical Aesthetics, Allergan. Upon completion of the Allergan acquisition, Strom was named senior VP, AbbVie and president, Global Allergan Aesthetics. She now oversees the worldwide operations, along with an experienced team of current Allergan leaders, and reports directly to Gonzalez.

The Eye Care and Specialty businesses – including Botox Therapeutic, Central Nervous System, Women’s Health, and Gastrointestinal Diseases – are being integrated into the existing AbbVie organization. Several Allergan leaders have accepted leadership positions across these franchises.

Other acquisitions & partnerships

In June, AbbVie and Genmab A/S signed a broad collaboration agreement to jointly develop and commercialize three of Genmab’s early-stage investigational bispecific antibody product candidates and enter into a discovery research collaboration for future differentiated antibody therapeutics for cancer. The companies are partnering to develop Genmab’s next-generation bispecific antibody programs, epcoritamab (DuoBody-CD3xCD20), DuoHexaBody-CD37 and DuoBody-CD3x5T4. According to company leaders, the collaboration combines Genmab’s world-class discovery and development engine and next-generation bispecific antibody therapeutic candidates with AbbVie’s deep clinical expertise, innovative antibody-drug conjugate platform, and global commercial leadership in hematological cancers.

The discovery research collaboration will combine proprietary antibodies from both companies along with Genmab’s DuoBody technology and Abb­Vie’s payload and ADC technology to select and develop up to four additional differentiated next-generation antibody-based product candidates, potentially across both solid tumors and hematological malignancies. Genmab’s DuoBody-CD3 technology engages and directs cytotoxic T cells selectively to tumors to elicit an immune response towards malignant tumor cells. AbbVie’s ADC technology allows the delivery of a therapeutic toxin directly to cancer cells while sparing normal, healthy cells, providing for a more targeted, less toxic treatment approach.

For epcoritamab, the companies will share commercial responsibilities in the United States and Japan, with AbbVie responsible for further global commercialization. Genmab will book net sales in the U.S. and Japan and receive tiered royalties on remaining global sales. For DuoHexaBody-CD37, DuoBody-CD3x5T4 and any product candidates developed as a result of the companies’ discovery research collaboration, Genmab and AbbVie will share responsibilities for global development and commercialization in the United States and Japan. Genmab retains the right to co-commercialize these products, along with AbbVie, outside of the U.S. and Japan. For the discovery research partnership, Genmab will conduct Phase I studies for these programs. AbbVie retains the right to opt-in to program development.

Also in June, AbbVie, Harbour BioMed, Utrecht University and Erasmus Medical Center entered into a collaboration to develop a novel antibody therapeutic to prevent and treat COVID-19, the pandemic respiratory disease caused by the SARS-CoV-2 virus. The focus of the collaboration is on advancing the fully human, neutralizing antibody 47D11 discovered by UU, EMC, and HBM. This antibody targets the conserved domain of the spike protein of SARS-CoV-2.

Under the terms of the collaboration, AbbVie will support UU, EMC, and HBM through the preclinical activities, while simultaneously undertaking preparations for later-stage preclinical and clinical development work. AbbVie will receive an option to exclusively license the antibody from the three parties for therapeutic clinical development and commercialization worldwide.

Also in June, AbbVie and Jacobio Pharmaceuticals, a clinical-stage pharmaceutical company, announced a global strategic collaboration to develop and commercialize SHP2 inhibitors, which target a key node in cancer and immune cells. SHP2 is an important protein mediator of cellular signaling through RAS/MAP kinase pathway. Many tumors have genetic mutations, driving abnormal cancer cell growth which relies on SHP2 activity. SHP2 also plays a key role to control cytokine production and immune cell response. Therefore, inhibition of SHP2 is believed to have dual effects by potentially reducing cancer cell growth and modulating immune responses to generate anti-tumor activities. Jacobio’s early clinical-stage SHP2 assets, JAB-3068 and JAB-3312, are oral small molecules designed to specifically inhibit SHP2 activity.

Under the terms of the agreement, AbbVie will be granted an exclusive license to the SHP2 portfolio. Jacobio will continue to conduct early global clinical trials of JAB-3068 and JAB-3312 with AbbVie covering R&D expenses. Upon completion, Abb­Vie will assume global development and commercialization responsibilities. Jacobio has an option, exercisable before the initiation of registrational trials, to exclusively develop and commercialize the SHP2 program in mainland China, Hong Kong, and Macau. Financial terms were not disclosed.

In August, AbbVie and its fellow COVID R&D Alliance members Amgen and Takeda announced the first patients were enrolled in the I-SPY COVID Trial (Investigation of Serial Studies to Predict Your COVID Therapeutic Response with Biomarker Integration and Adaptive Learning) clinical trial. The I-SPY COVID Trial will evaluate the efficacy of cenicriviroc, a chemokine (CCR2 and CCR5) dual-receptor antagonist, Otezla (apremilast), a PDE4 inhibitor, and Firazyr (icatibant injection), a bradykinin B2 receptor antagonist in severely ill, hospitalized COVID-19 patients who require high-flow oxygen. The I-SPY COVID Trial utilizes Quantum Leap Healthcare Collaborative’s adaptive platform trial design, which is intended to increase trial efficiency by minimizing the number of participants and time required to evaluate potential treatments.

The study is a collaboration between members of the COVID R&D Alliance, Quantum Leap, and FDA. AbbVie, Amgen, and Takeda are members of the COVID R&D Alliance, a group of more than 20 of the world’s leading biopharmaceutical and life science companies working to speed the development of potential therapies, novel antibodies, and anti-viral therapies for COVID-19 and its related symptoms.

The therapies under investigation were selected based on their potential to impact the immune system response of COVID-19 patients who need respiratory support. About 10-15 percent of patients afflicted by COVID-19 develop acute respiratory distress syndrome, and up to 60 percent of those patients admitted to an ICU require ventilation for an average of two weeks. It is estimated that half of those patients will not survive. Based on the respective mechanisms of action, Otezla may suppress inflammation resulting from an immune response, Firazyr may ameliorate bradykinin-driven pulmonary edema, and cenicriviroc acts by blocking monocytes trafficking to tissues, features that may help to reduce or mitigate the severity of ARDS response in severely ill COVID-19 patients.

In September, AbbVie and I-Mab signed a broad, global collaboration agreement for the development and commercialization of lemzoparlimab (also known as TJC4), an innovative anti-CD47 monoclonal antibody internally discovered and developed by I-Mab for the treatment of multiple cancers. In addition, the two partners have the potential to expand the collaboration to additional transformative therapies. 

Lemzoparlimab is one of the leading drug candidates among I-Mab’s proprietary and innovative pipeline. The compound is designed to minimize inherent binding to normal red blood cells while preserving its strong anti-tumor activity, a critical attribute in potentially differentiating lemzoparlimab from other antibodies of the same class currently in development. Topline results of the recent Phase I clinical trial confirmed possible differentiation of lemzoparlimab in drug safety and a more favorable pharmacokinetics profile in cancer patients. Results have shown that lemzoparlimab is well tolerated as a single agent at a dose range of up to 30 mg/kg without any priming dose. In all DLT-evaluable patients, no dose-limiting toxicities or severe hematologic adverse events were observed.

The collaboration provides AbbVie with an exclusive global license, excluding greater China, to develop and commercialize lemzoparlimab. Both companies will collaborate to design and conduct further global clinical trials to evaluate lemzoparlimab in multiple cancers. I-Mab retains all rights to develop and to commercialize lemzoparlimab in mainland China, Macau, and Hong Kong. The collaboration also allows for potential collaboration on future CD47-related therapeutic agents. Each party will have the opportunity subject to further licenses to explore each other’s related programs in their respective territories. The companies will share manufacturing responsibilities with AbbVie being the primary manufacturer for global supply. The collaboration will accelerate I-Mab’s establishment of commercial production operations in China.

Product performances

For the first time in the product’s 16-year market history, sales of Humira actually declined in 2019. Of course even with a 3.8 percent decline, Humira still brought in $19.17 billion in revenue, good enough for first place among all prescription products worldwide – again – by a margin of more than $8 billion. According to AbbVie executives, the decline was due to biosimilar competition around the world, which caused a 31.1 percent decline in sales internationally; in the United States, Humira sales in 2019 grew 8.6 percent to $14.86 billion. In the first half of 2020, total Humira sales rose 2.4 percent to $9.54 billion globally, once again driven by domestic growth; while sales were up 8.9 percent stateside, international sales declined by 17.2 percent, again due to biosimilar competition. 

AbbVie’s leading oncologic Imbruvica enjoyed an impressive year in 2019, with sales jumping 30.2 percent to $4.67 billion. Company leaders credited this growth to continued market penetration in CLL as well as favorable pricing. In the first half of 2020, Imbruvica sales rose another 18.8 percent to $2.52 billion.

In April, FDA approved the use of Imbruvica in combination with rituximab for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This milestone marks the 11th FDA approval for Imbruvica since the product was first approved in 2013 and the sixth in CLL, the most common form of leukemia in adults.

The approval was based on positive results from the landmark Phase III E1912 study, which was designed and conducted by the ECOG-ACRIN Cancer Research Group and sponsored by the National Cancer Institute, part of the National Institutes of Health. This is the third Phase III randomized study in the treatment of previously untreated CLL patients incorporated into the medicine’s U.S. prescribing information. In addition to the Real-Time Oncology Review pilot program and priority review, the approval was granted under FDA’s recently established Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for submission and review of oncology medicine applications among multiple regulatory agencies worldwide.

The E1912 study demonstrated previously untreated patients (aged 70 or younger) with CLL lived longer without disease progression – as measured by statistically significant progression-free survival (PFS) – with Imbruvica plus rituximab compared to those treated with the potent chemoimmunotherapy regimen comparator of fludarabine, cyclophosphamide and rituximab (FCR). At a median follow-up of 37 months, Imbruvica plus rituximab significantly improved PFS compared to FCR. With a median follow-up time of 49 months, median overall survival was not reached with a total of 23 deaths: 11 (3 percent) in the Imbruvica plus rituximab and 12 (7 percent) in the FCR treatment arms.

In June, FDA accepted for review a supplemental new drug application for Imbruvica in combination with rituximab for the treatment of Waldenström’s macroglobulinemia, a rare and incurable type of non-Hodgkin’s lymphoma. The application seeks to update the Imbruvica U.S. Prescribing Information based on analysis of more than five years of data from the Phase III iNNOVATE clinical trial. Imbruvica was first approved as a single agent therapy for all lines of WM in 2015, becoming the first FDA-approved medicine for WM, administered orally. In 2018, Imbruvica was also approved as the first chemotherapy-free combination treatment with rituximab. As of the date of the sNDA, Imbruvica is the only Bruton’s tyrosine kinase (BTK) inhibitor approved to treat WM.

The hepatitis C product Mavyret/Maviret suffered a 15.9 percent sales decline in 2019, falling to $2.89 billion due to lower patient volumes in certain international markets and increased competition in the United States. The slide grew more pronounced in the first half of 2020, with sales declining by 40.4 percent to $935 million, pushed along again by lower patient volumes internationally and domestic competition, plus the effect of lower new patient starts due to COVID-19. 

In March, the European Commission approved a change to the marketing authorization for Maviret to shorten once-daily treatment duration from 12 to 8 weeks in treatment-naïve, compensated cirrhotic, chronic hepatitis C patients with genotype 3 infection. Maviret was already indicated as an 8-week, pan-genotypic (GT1-6), once-daily regimen for treatment-naïve HCV patients without cirrhosis, and as an 8-week, once-daily regimen for treatment-naïve GT 1, 2, 4, 5, and 6 HCV patients with compensated cirrhosis.

The EC approval was supported by data from the Phase IIIb EXPEDITION-8 study. This study evaluated the safety and efficacy of Maviret in treatment-naïve chronic HCV patients with compensated cirrhosis across all major genotypes. The results have been reported for GT1, 2, 3, 4, 5, and 6 patients and showed that with 8 weeks of Maviret, 97.7 percent of GT1-6 patients achieved a sustained virologic response 12 weeks after treatment (SVR12). For patients with GT3, the SVR12 rate was 95.2 percent. 

AbbVie’s most impressive sales-growth performer in the first half of 2020 was the plaque psoriasis drug Skyrizi. The biologic rolled up $630 million in sales for the half, more than 13 times what the drug earned in the first half of 2019 after earning its first U.S. approval in April of that year. 

In June, AbbVie announced Phase IIIb head-to-head data showing superior rates of skin clearance for Skyrizi to Cosentyx at week 52. Particularly, 66 percent of psoriasis patients receiving Skyrizi achieved completely clear skin – 100 percent clearance in the Psoriasis Area and Severity Index (PASI 100) – versus 40 percent of patients receiving Cosentyx at week 52.

Skyrizi met both PASI 90 primary endpoints of non-inferiority to Cosentyx at week 16 and superiority to Cosentyx at week 52. At week 16, 74 percent of Skyrizi-treated patients achieved PASI 90 compared to 66 percent of Cosentyx-treated patients. Of patients treated with Skyrizi, 87 percent achieved PASI 90 at week 52 compared to 57 percent of Cosentyx-treated patients. 

Additional results demonstrated a significantly higher proportion of patients treated with Skyrizi achieved a static Physician Global Assessment (sPGA) score of clear or almost clear (sPGA 0/1) compared to those treated with Cosentyx at week 52 (88 percent versus 58 percent, respectively).

First-half 2020 sales for the oncologic medicine Venclexta/Venclyxto (venetoclax) nearly doubled, rising from $320 million in first-half 2019 to $620 million. According to company leaders, this was due to continued expansion for the treatment of patients with first-line CLL and relapsed/refractory CLL.

In February, AbbVie announced that the VIALE-C (M16-043) trial of Venclexta in combination with low-dose cytarabine (LDAC) versus LDAC in combination with placebo did not meet its primary endpoint of statistically significant improvement of overall survival for patients with acute myeloid leukemia who are ineligible for intensive chemotherapy at the time of the planned analysis.

Treatment with the venetoclax combination showed a 25 percent reduction in the risk of death compared to LDAC with placebo. The venetoclax with LDAC arm also showed a median OS of 7.2 months versus 4.1 months in the LDAC arm alone. A post-hoc analysis after an additional six months of follow up showed an increase in median OS of 8.4 months in the venetoclax plus LDAC arm and 4.1 months in the placebo plus LDAC arm.

In March, the European Medicines Agency approved Venclyxto in combination with obinutuzumab for the treatment of adult patients with chronic lymphocytic leukemia (CLL) who were previously untreated. This was the third approval for Venclyxto, a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor. BCL-2 is a protein that prevents cancer cells from undergoing apoptosis, the process that leads to the natural death or self-destruction of cancer cells. Venclyxto is also approved in combination with rituximab for the treatment of adult patients with CLL who have received at least one prior therapy, and as a monotherapy for the treatment of CLL in the presence or absence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor. Venclyxto is being developed by AbbVie and Roche, and is being jointly commercialized by AbbVie and Genentech, a member of the Roche group, in the United States and by AbbVie outside of the U.S. 

The approval was based on results from the Phase III CLL14 clinical trial primary analysis (median follow up of 28 months), which demonstrated superior progression-free survival (PFS; the time on treatment without disease progression or death) as assessed by investigators in patients treated with Venclyxto plus obinutuzumab compared to patients who received a standard of care chemotherapy regimen of chlorambucil plus obinutuzumab. At an updated CLL14 efficacy analysis (median follow-up of 40 months), the median PFS had not been reached in the Venclyxto + obinutuzumab arm and was 35.6 months in the obinutuzumab + chlorambucil arm. The 36-month PFS estimate in the venetoclax plus obinutuzumab arm was 81.9 percent and in the obinutuzumab plus chlorambucil arm was 49.5 percent. Additionally, after completing one year of treatment, patients treated with the Venclyxto combination experienced deep response as measured by higher rates of undetectable minimal residual disease (MRD) or complete response (CR) as compared to patients receiving a standard of care regimen.

In August, AbbVie announced the publication of results from the Phase III VIALE-A clinical study in patients with AML in the New England Journal of Medicine. The study, which evaluated newly diagnosed acute myeloid leukemia patients who had not yet been treated and were unable to tolerate traditional intensive chemotherapy, found that Venclexta in combination with azacitidine extended overall survival compared to azacitidine plus placebo.

In the VIALE-A study, OS was the sole primary study endpoint in the United States. OS and composite complete remission rate (CR+CRi) were co-primary endpoints in China, Japan, the European Union, and EU reference countries. CR+CRi is a composite score reflecting the complete remission and CR with incomplete hematologic recovery, which is an incomplete CR with blood counts not fully recovered. Treatment with venetoclax plus azacitidine reduced the risk of death by 34 percent compared to azacitidine in combination with placebo.

Patients in the venetoclax combination arm had a median OS of 14.7 months versus 9.6 months for patients in the placebo arm. Additionally, 66.4 percent of patients treated with venetoclax plus azacitidine achieved CR+CRi versus 28.3 percent of patients treated with azacitidine plus placebo. Other secondary endpoints that were published in NEJM include CR and CR with partial hematologic recovery (CR+CRh).

Moving into AbbVie’s portfolio after completion of the Allergan acquisition on May 8, Botox generated $297 million in therapeutic sales and $226 million in cosmetic sales between that date and the end of the first half of 2020. While still under the Allergan umbrella, Botox generated therapeutic sales of $1.74 billion and cosmetic sales of $991 million in full-year 2019. 

In June, FDA accepted a supplemental biologics license application to expand the Botox prescribing information for the treatment of signs and symptoms of detrusor (bladder muscle) overactivity associated with an underlying neurologic condition (e.g., spina bifida, spinal cord injuries) in pediatric patients (5-17 years of age) who have an inadequate response to, or are intolerant of, or for any reason unwilling to continue anticholinergic medication. 

The sBLA was based on data from a randomized, double-blind Phase III study evaluating the safety and efficacy of Botox in more than 100 pediatric patients with neurogenic detrusor overactivity and a long-term extension study. The Prescription Drug User Fee Act date is expected to be in the first quarter of 2021 following a standard 10-month review.

In July, FDA approved a supplemental biologics license application that supports expanded use of Botox for the treatment of spasticity in pediatric patients 2 years of age and older, including those with lower limb spasticity caused by cerebral palsy. This label expansion is based on Allergan and another manufacturer selectively waiving orphan exclusivity marketing rights each company held for the use of their respective neurotoxins in the treatment of pediatric patients with spasticity caused by cerebral palsy. Botox was first approved in June 2019 for the treatment of pediatric patients with upper limb spasticity and in October 2019 for the treatment of pediatric patients with lower limb spasticity, excluding spasticity caused by cerebral palsy. The safety and efficacy of Botox as treatment for lower limb spasticity for pediatric patients is supported by a Phase III study with more than 300 patients two to 17 years of age with lower limb spasticity because of cerebral palsy. These trials included a 12-week, double-blind study, and a one-year open-label extension study.

In the pipeline

FDA during May approved Oriahnn (elagolix, estradiol, and norethindrone acetate capsules; elagolix capsules), with a treatment duration of up to 24 months. Oriahnn is the first FDA-approved non-surgical, oral medication option for the management of heavy menstrual bleeding associated with uterine fibroids in pre-menopausal women. The product was developed by AbbVie and Neurocrine Biosciences.

In the two, randomized Phase III uterine fibroid clinical trials, ELARIS UF-I and ELARIS UF-II, Oriahnn achieved the primary endpoint of clinically meaningful reduction in bleeding (defined as the proportion of women who achieved both at least a 50 percent reduction in menstrual blood loss at final month of treatment and a total menstrual blood loss amount of less than 80 milliliters), compared with placebo in final month of study for patients, with seven out of 10 women no longer experiencing heavy menstrual bleeding versus one out of 10 women on placebo. Oriahnn also reduced heavy menstrual bleeding due to uterine fibroids by 50 percent within the first month of use.

In June, AbbVie submitted applications for a new indication to FDA and EMA for Rinvoq for the treatment of adult patients with active psoriatic arthritis. The applications were supported by data from two Phase III studies across a broad range of more than 2,000 patients with active psoriatic arthritis. In both studies, Rinvoq met the primary endpoint of ACR20 response at week 12 versus placebo. Rinvoq 15 milligrams also achieved non-inferiority versus adalimumab in terms of ACR20 response at week 12.1 Patients receiving Rinvoq also experienced greater improvements in physical function (HAQ-DI) and skin symptoms (PASI 75), and a greater proportion achieved minimal disease activity. Overall, the safety profile of Rinvoq in psoriatic arthritis was consistent with previously reported results across the Phase III rheumatoid arthritis clinical trial program, with no new significant safety risks detected.

Also in June, Allergan and Molecular Partners, a clinical-stage biotechnology company developing a new class of custom-built protein therapeutics known as DARPin therapeutics, received a Complete Response Letter from FDA to the biologics license application for Abicipar pegol, a novel, investigational DARPin therapy for patients with neovascular (wet) age-related macular degeneration. 

The letter from FDA indicated that the rate of intraocular inflammation observed following administration of Abicipar pegol 2mg/0.05 mL results in an unfavorable benefit-risk ratio in the treatment of neovascular (wet) age-related macular degeneration. AbbVie plans to meet with FDA to discuss their comments and determine next steps.

Also in June, AbbVie announced new data from a Phase IIa study of ABBV-3373, an investigational anti-tumor necrosis factor (TNF) glucocorticoid receptor modulator (GRM) steroid antibody drug conjugate (ADC), in adult patients with moderate to severe rheumatoid arthritis. The primary endpoint was the change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) from baseline to week 12 and two statistical comparisons were pre-specified. The first compared ABBV-3373 and mean outcome from historical adalimumab data. The second compared ABBV-3373 and combined in-trial and historical adalimumab data. Results of the first comparison show a greater difference in the primary endpoint change in DAS28-CRP from baseline to week 12 for ABBV-3373 (-2.65) as compared to a pre-specified historical adalimumab mean (-2.13). Results of the second comparison, based on a Bayesian analysis, predicted with a 90 percent probability that ABBV-3373 was associated with a greater improvement on DAS28-CRP from baseline to week 12 than adalimumab based on in-trial data combined with historical data. Additionally, evaluations of serum cortisol levels over 12 weeks indicate that ABBV-3373 showed no systemic glucocorticoid effects.

Also in June, AbbVie announced new Phase III data from the SELECT-CHOICE clinical trial, showing that Rinvoq met the primary endpoint of non-inferiority versus Orencia on change from baseline in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) at week 12 in rheumatoid arthritis patients. In addition, Rinvoq met the key secondary endpoints of superiority versus Orencia on change from baseline in DAS28-CRP at week 12 and proportion of patients achieving clinical remission at week 12 as measured by DAS28-CRP<2.6. ACR20/50/70 responses were also higher in the Rinvoq group compared to the Orencia group (76/46/22 percent versus 66/34/14 percent, respectively) at week 12. Improvements in disease activity and remission rates were maintained through 24 weeks. The study evaluated Rinvoq in adult patients with moderate to severe active rheumatoid arthritis and prior inadequate response or intolerance to biologic disease-modifying anti-rheumatic drugs (DMARDs). SELECT-CHOICE is the sixth and final Phase III study from the robust SELECT rheumatoid arthritis clinical trial program.

In July, AbbVie announced that the Phase III ADVANCE trial evaluating the investigational medicine atogepant, an orally administered calcitonin gene-related peptide receptor antagonist (gepant), met its primary endpoint of statistically significantly greater reduction in mean monthly migraine days, compared to placebo, for all doses across the 12-week treatment period. With these results, combined with the prior positive Phase II/III trial, AbbVie plans to move forward with regulatory submissions in the United States and other countries.

The pivotal Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those with 4 to 14 migraine days per month. A total of 910 patients were randomized to one of four treatment groups evaluating 10 milligrams, 30 milligrams, or 60 milligrams of atogepant once daily, or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.

The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated statistically significantly greater decreases in mean monthly migraine days compared to placebo. Patients treated in the 10 mg/30 mg/60 mg atogepant arms experienced a decrease of 3.69/3.86/4.2 days, respectively, all compared to patients in the placebo arm, who experienced a decrease of 2.48 days.

A key secondary endpoint measured the proportion of patients that achieved at least a 50 percent reduction in mean monthly migraine days across the 12-week treatment period. The trial demonstrated that 55.6 percent/58.7 percent/60.8 percent of patients in the 10 mg/30 mg/60 mg atogepant arms, respectively, achieved at least a 50 percent reduction, compared to 29.0 percent of patients in the placebo arm.

Additional secondary endpoints measured across the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute-medication use days, and mean monthly performance of daily activities and physical impairment domain scores of the Activity Impairment in Migraine-Diary (AIM-D), and change from baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score at week 12. The trial demonstrated that treatment with 30 milligrams and 60 milligrams doses resulted in statistically significant improvements in all secondary endpoints, while treatment with the 10 milligrams dose resulted in statistically significant improvements in four out of the six secondary endpoints.

Also in July, AbbVie announced that upadacitinib (15 mg and 30 mg, once daily) plus topical corticosteroids (TCS) met the co-primary endpoints and all secondary endpoints in AD Up, the third pivotal Phase III study of Rinvoq in atopic dermatitis. AD Up evaluated the efficacy and safety of both doses of upadacitinib therapy versus placebo in adults and adolescents with moderate to severe atopic dermatitis; all treatment groups, including placebo, received concomitant TCS. The co-primary endpoints were at least a 75 percent improvement in the Eczema Area Severity Index (EASI 75) from baseline and a validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at week 16. AbbVie had previously announced positive results from two additional Phase III studies of upadacitinib in atopic dermatitis, Measure Up 1 and Measure Up 2.

Significantly more patients receiving either dose of upadacitinib plus TCS showed improvement in skin clearance compared to placebo plus TCS at week 16. In the study, 65/77 percent of patients receiving upadacitinib 15/30 mg plus TCS achieved EASI 75, respectively, versus 26 percent receiving placebo plus TCS. Of patients treated with upadacitinib 15/30 mg plus TCS, 40/59 percent achieved vIGA-AD 0/1, respectively, versus 11 percent of patients receiving placebo plus TCS.

Additionally, more patients treated with upadacitinib plus TCS experienced a clinically meaningful reduction in itch, defined as improvement in Worst Pruritus Numerical Rating Scale (NRS)≥4, compared to patients treated with placebo plus TCS. At week 16, 52/64 percent of patients receiving upadacitinib 15/30 mg plus TCS achieved this endpoint compared to 15 percent of patients receiving placebo plus TCS.

In a pre-specified additional analysis, treatment with either dose of upadacitinib also led to a higher mean number of topical corticosteroid-free days (TCS-free days) up to week 16 versus placebo. A TCS-free day is defined by a response of EASI 75 or greater without the use of TCS. Patients treated with upadacitinib 15/30 mg had a mean of 34/47 TCS-free days while maintaining EASI 75, respectively, compared with a mean of 8 days for those treated with placebo plus TCS. 

In August, AbbVie submitted an application for a new indication to FDA for Rinvoq for the treatment of adult patients with active ankylosing spondylitis. AbbVie also submitted an application to the European Medicines Agency for Rinvoq earlier in 2020 for the treatment of adult patients with active ankylosing spondylitis who have responded inadequately to conventional therapy.

The applications to FDA and EMA are supported by data from SELECT-AXIS 1, a Phase II/III study in which Rinvoq demonstrated significant improvements in signs and symptoms in patients with active ankylosing spondylitis. In this study, twice as many patients receiving Rinvoq (52 percent) met the primary endpoint of Assessment of SpondyloArthritis International Society (ASAS) 40 response versus placebo (26 percent) at week 14. The safety profile of Rinvoq in ankylosing spondylitis was consistent with previously reported studies across therapeutic areas, including rheumatoid arthritis, atopic dermatitis and psoriatic arthritis, with no new significant safety risks detected. 

Rinvoq was approved in August 2019 by FDA for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, Rinvoq was approved by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. Phase III trials of Rinvoq in psoriatic arthritis, rheumatoid arthritis, axial spondyloarthritis, Crohn’s disease, atopic dermatitis, ulcerative colitis, and giant cell arteritis are under way.