AbbVie 2018: Still Humira
While other products are showing signs of growth, the fate of AbbVie is still in the hands of the iconic autoimmune drug.
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AbbVie was still very much the Humira company in 2017 and the first half of 2018. Sales of the autoimmune drug made up nearly two-thirds of the company’s top line last year, and more than 60 percent of it this past January through June. And that does not seem likely to change any time soon; over the past year, AbbVie worked out arrangements with potential biosimilar competitors that should allow the product to maintain its U.S. market exclusivity through early 2023.
That said, the company does have other positive developments brewing in the portfolio. Helped by positive clinical trial data and a new indication from FDA, the oncology drug Imbruvica has been showing impressive sales growth. Revenue from the new HCV compound Mavyret has blown up in the past year. And company leaders are confident that the AbbVie pipeline, led by the recently approved oncology drug Venclexta and the developmental autoimmune compounds upadacitinib and risankizumab, offers hope for the world after Humira.
“Our future has never looked better,” says Richard A. Gonzalez, chairman and CEO, AbbVie. “Humira, the most widely prescribed autoimmune biologic therapy, will continue to be an important growth driver for several years. In 2017, we reached global resolution of our most advanced patent litigation regarding Humira. Beyond Humira, our portfolio of on-market therapies, combined with the significant potential of our late-stage pipeline is expected to generate more than $35 billion in revenue in 2025.”
AbbVie’s top-line revenue was about $28.22 billion in 2017, an improvement of 10.1 percent over the previous year. The growth came primarily thanks to improvement in sales of Humira and Imbruvica, offset by a drop-off in sales of the HCV product Viekira. Net income for the year was down 10.8 percent to $5.31 billion and earnings per share dropped 33 cents to $3.30, though company leaders say this result was impacted by a one-time mandatory repatriation of previously untaxed earnings of foreign subsidiaries. In the first half of 2018 the impressive growth of Mavyret helped push AbbVie’s revenue up 20.2 percent to $16.21 billion, with net income rising 31.4 percent to $4.77 billion and EPS growing 74 cents to $2.99. Company leaders projected full-year EPS for 2018 will be between $6.47 and $6.57.
Humira remained the leading prescription medicine by global revenue for the sixth consecutive year in 2017, and by an even greater margin than before – AbbVie’s reported sales of $18.43 billion were more than $10 billion greater than world No. 2 Revlimid. Humira sales were up 14.6 percent for the year; according to company leaders this was due to market growth across therapeutic categories and geographies as well as favorable pricing in certain geographies. In the first half of 2018, Humira sales for AbbVie were up another 12 percent to $9.89 billion.
In July, AbbVie announced patent license deals with Mylan over its proposed biosimilar adalimumab product. Under the terms of the agreements, AbbVie will grant Mylan a non-exclusive license on specified dates to AbbVie’s intellectual property relating to Humira in the United States and in various other countries around the world in which AbbVie has intellectual property, excluding Europe.
Mylan’s U.S. license will begin on July 31, 2023, and will not be accelerated by Amgen’s or Samsung Bioepis’ product entry. Mylan will pay royalties to AbbVie for licensing its Humira patents once the biosimilar product is launched.
Mylan acknowledges the validity of the licensed patents. AbbVie will make no payments to Mylan.
“AbbVie’s Humira patents reflect the groundbreaking work of AbbVie scientists in the field of fully human biologics and our investment in patient-focused innovation,” says Laura Schumacher, executive VP, external affairs, general counsel and corporate secretary, AbbVie. “We understand the importance of balancing innovation and accessibility, and our agreement with Mylan for its Humira biosimilar maintains that balance.”
On Sept. 28, 2017, AbbVie announced a global resolution with Amgen to enter the United States market on Jan. 31, 2023.
On April 5, 2018, AbbVie announced a similar resolution with Samsung Bioepis to enter the United States marketplace on June 30, 2023.
Firming up the drug’s place in AbbVie’s second spot, the oncology compound Imbruvica generated $2.57 billion in sales for the company in 2017, an impressive improvement of 40.4 percent over the previous year. According to company leaders, this was as a result of continued penetration of Imbruvica as a first-line treatment for patients with CLL as well as favorable pricing. In the first half of 2018, Imbruvica sales for AbbVie rose 37 percent to $1.61 billion.
In May, AbbVie announced that the Phase III iLLUMINATE (PCYC-1130) trial met its primary endpoint of improvement in progression-free survival (PFS). The study evaluated Imbruvica in combination with Gazyva in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) patients, the most common adult leukemia. Specifically, the study met its primary endpoint for a clinically and statistically significant difference in PFS for patients treated with Imbruvica plus Gazyva versus those who received chlorambucil plus Gazyva, as assessed by an Independent Review Committee.
During June, AbbVie announced positive clinical data from the Phase II CAPTIVATE (PCYC-1142) study evaluating Imbruvica in combination with the company’s product Venclexta in previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma patients. Early results of the combination oral regimen suggest promising activity in treatment-naïve CLL/SLL with 77 percent of the first 30 patients achieving responses with no detectable minimal residual disease (MRD) after six cycles of the combination therapy. MRD is determined by measuring the number of cancer cells remaining and helps confirm depth of remission. The first 14 CLL/SLL patients to complete the clinical trial combination therapy of 12 cycles (15 cycles of Imbruvica) achieved responses with no detectable MRD in nine out of 10 patients, with 93 percent achieving MRD negativity when measuring in peripheral blood and 86 percent with MRD negativity when measuring in the bone marrow.
During July, AbbVie announced an update on a Phase III study (DBL3001) of Imbruvica in untreated (treatment-naïve) diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin lymphoma (NHL). The DBL3001 study evaluated the addition of Imbruvica to a chemotherapy regimen consisting of five different agents used in combination – rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) – versus R-CHOP plus placebo. R-CHOP is the current standard of care in newly diagnosed DLBCL patients and provided as a first-line therapy for most patients today. The study was conducted in a subset of untreated DLBCL patients identified to have the non-germinal center B cell (GCB) or activated B-cell (ABC) subtypes of this disease. Patients identified with non-GCB or ABC subtypes typically have poorer treatment outcomes and have greater unmet medical need.
At the conclusion of the study, data collected found that Imbruvica plus the chemotherapy regimen, R-CHOP, was not superior to R-CHOP alone, and that the study did not meet its primary endpoint of improving event-free survival (EFS) in the targeted patient population. However, clinically meaningful improvements were observed in a patient sub-population that warrant further analysis.
In August, FDA approved Imbruvica plus rituximab for the treatment of adult patients with Waldenström’s macroglobulinemia (WM), a rare and incurable type of non-Hodgkin’s lymphoma. With this approval, the Imbruvica prescribing information now includes combination use with rituximab, representing the first chemotherapy-free combination treatment specifically indicated for the disease. Imbruvica was initially approved as a single agent therapy for WM in January 2015. Imbruvica is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Pharmacyclics LLC – an AbbVie company – and Janssen Biotech Inc.
“We are pleased to have Imbruvica approved, both as a single agent and combination therapy with rituximab, to provide an additional efficacious treatment option for people living with Waldenström’s macroglobulinemia,” says Thorsten Graef, M.D., Ph.D., head of clinical development at Pharmacyclics. “We are proud of our robust clinical development program, and this new approval reflects our continuous commitment to exploring the full potential of Imbruvica’s mechanism of action for treating patients with diseases that have great unmet medical need.”
The new FDA approval was supported by data from the Phase III iNNOVATE (PCYC-1127) trial evaluating Imbruvica in combination with rituximab, versus rituximab alone, in 150 patients with previously untreated and relapsed/refractory WM. At a median follow up of 26.5 months, the study demonstrated a significant improvement in progression-free survival with Imbruvica plus rituximab compared to rituximab alone (30-month PFS rates were 82 percent versus 28 percent, respectively). Patients taking Imbruvica plus rituximab also experienced an 80 percent reduction in relative risk of disease progression or death than those only treated with rituximab.
Sales of AbbVie’s HCV portfolio fell off by 16.3 percent in 2017 to $1.27 billion. According to company leaders, this was a result of market contraction, lower market share and price erosion of Viekira. However, powered by the launch of Mavyret (approved by the EC in July 2017 and FDA in August 2017) in certain geographies, AbbVie’s HCV sales more than quadrupled in the first half of 2018, to $1.89 billion. According to published reports, by the end of second-quarter 2018 Mavyret was picking up half of all new HCV prescriptions in the United States.
ACQUISITIONS & COLLABORATIONS
In February, AbbVie and Voyager Therapeutics Inc. – a clinical-stage gene therapy company – announced an exclusive strategic collaboration and option agreement to develop and commercialize vectorized antibodies directed against tau for the treatment of Alzheimer’s disease and other neurodegenerative diseases. This collaboration, company leaders say, combines AbbVie’s monoclonal antibody expertise, global clinical development and commercial capabilities with Voyager’s gene therapy platform and expertise that enables generating adeno-associated viral (AAV) vectors for the treatment of neurodegenerative diseases.
In healthy individuals, tau is an abundant protein in the brain that promotes cellular stability and function. In the diseased brain, altered tau accumulates, resulting in impaired brain function and neuronal cell loss. The progressive spread of abnormal tau in the brain closely correlates with progressive neurodegeneration and symptom severity. However, one of the current limitations with the use of weekly or biweekly infusions of biologic therapies for neurodegenerative diseases is that only a small amount of drug is able to make its way into the brain. This collaboration seeks to develop a potential one-time treatment using Voyager’s gene therapy platform to reduce tau pathology through the delivery of an AAV vector antibody that encodes the genetic instructions to produce anti-tau antibodies within the brain.
Under the terms of the collaboration and option agreement, Voyager will perform research and preclinical development of vectorized antibodies directed against tau, after which AbbVie may select one or more vectorized antibodies to proceed into IND-enabling studies and clinical development. Voyager is responsible for the research, IND-enabling and Phase I studies activities and costs. Following completion of Phase I clinical development, AbbVie has an option to license the vectorized tau antibody program and would then lead further clinical development and global commercialization for tauopathies, including Alzheimer’s disease and other neurodegenerative diseases. Voyager has an option to share in the costs of clinical development for higher royalty rates.
Voyager will receive an upfront cash payment of $69 million as well as up to $155 million in potential preclinical and Phase I option payments. In addition, Voyager is eligible to receive up to $895 million in development and regulatory milestones for each vectorized tau antibody compound and is eligible to receive tiered royalties on the global commercial net sales of the vectorized antibodies for tauopathies, including Alzheimer’s disease and other neurodegenerative diseases.
During March, AbbVie and the International Myeloma Foundation (IMF) announced a collaboration to conduct a landmark retrospective chart review study to better understand and help manage multiple myeloma (MM), the second most common blood cancer.
The primary objective of the study is to determine the overall survival of patients with MM and the t(11;14) translocation, which is present in an estimated 16 to 24 percent of FISH-tested MM cases. IMF researchers from at least 30 participating sites across the world will retrospectively review and characterize the outcomes of 1,500 patients with the t(11;14) translocation identified on FISH, making this study one of the largest and most comprehensive MM studies to date. Secondary objectives include response rates, progression-free survival, time to progression, time to next treatment, duration of responses and overall survival with different regimens among patients with the t(11;14) translocation.
Additional secondary objectives include determining prognostic factors for overall survival among MM patients with t(11;14) translocation and to identify the spectrum of co-existing genetic abnormalities among this patient population.
In April, AbbVie and Rice University announced a joint research collaboration to establish the K.C. Nicolaou Research Accelerator. The research at the Accelerator will focus on synthesizing novel cytotoxic agents for use in the fight against cancer. The collaboration, company leaders say, will complement AbbVie’s existing expertise in oncology discovery and early development.
The K.C. Nicolaou laboratory has expertise in the art of replicating complex natural molecules that have cancer-fighting properties. The process, called total synthesis, allows researchers to apply organic chemistry strategies and technologies to optimize anti-tumor agents. When combined with AbbVie’s medicinal chemistry and antibody engineering capabilities, executives say, these anti-tumor agents have the potential to transform cancer treatment paradigms and significantly benefit patients.
“Dr. Nicolaou and his team at Rice University are conducting world-class research in organic chemistry that has the potential to aid in the development of new and effective cancer therapies for patients,” says Tom Hudson, M.D., VP, oncology discovery and early development, AbbVie. “Our goal is to transform the way cancer is treated and we look forward to aligning our development capabilities with the team’s expertise in chemistry to better address patient needs.”
Dr. Nicolaou, the Harry C. and Olga K. Wiess Professor of Chemistry at Rice University, will lead the Accelerator’s research team at Rice. He achieved the first total synthesis of the widely used chemotherapy agent paclitaxel along with multiple other complex molecules. Dr. Nicolaou has received numerous prestigious awards, including the Wolf Prize in Chemistry in 2016 for advancing the field of chemical synthesis to the extremes of molecular complexity and expanding the interface among chemistry, biology and medicine.
During June, AbbVie and Calico – an Alphabet-backed life sciences company focused on aging research and therapeutics – announced an extension of their collaboration to discover, develop and bring to market new therapies for patients with age-related diseases, including neurodegeneration and cancer.
Calico is led by former Genentech chairman and CEO Arthur D. Levinson, Ph.D. With more than 150 employees, Calico has established a world-class research and development facility in the San Francisco Bay Area. Working together with AbbVie, Calico pursues discovery-stage research and development. AbbVie provides scientific and clinical development support and will lend its commercial expertise to lead future development and commercialization activities. Since 2014, the collaboration between the two companies has produced more than two dozen early-stage programs addressing disease states across oncology and neuroscience and yielded new insights into the biology of aging.
“We’ve built a successful collaboration – both scientifically and culturally – that is advancing cutting-edge science,” says Michael Severino, M.D., executive VP of research & development and chief scientific officer at AbbVie. “Calico has attracted an outstanding team of world-class scientists and the extension of this collaboration allows us to further build on the research we’ve done to identify transformative treatment options for patients with age-related diseases.”
The collaboration between the two companies is now extended for an additional three years. Calico is responsible for research and early development until 2022 and will advance collaboration projects through Phase IIa through 2027. AbbVie will continue to support Calico in its early R&D efforts and, following completion of Phase IIa studies, will have the option to manage late-stage development and commercial activities. Both parties will share costs and profits equally. AbbVie and Calico will each commit to contribute an additional $500 million to the collaboration.
Also in June, AbbVie and Calibr, a nonprofit drug discovery division of Scripps Research, announced a collaboration to develop T-cell therapies aimed primarily at cancer, including solid tumors. According to company leaders, this collaboration broadens AbbVie’s oncology research to access advanced precision medicine technology to expand the development of potentially life-changing treatments for patients with cancer.
Chimeric antigen receptor T-cell (CAR-T) therapies harness the power of a cancer patient’s own immune system to attack and destroy cancer cells. Despite promising results in hematological malignancies, current CAR-T therapies in development for solid tumors have demonstrated limitations due to rapid activation and expansion of CAR-T cells that can lead to serious adverse events. Calibr’s novel cell therapy program is designed to enhance safety, versatility, and efficacy through a proprietary modular “switchable” CAR-T cell that uses antibody-based switch molecules to control the activation and antigen specificity of CAR-T cells. Calibr’s proprietary technology may enable the development of universal CAR-T-based treatments across several types of hematological and solid tumor indications.
“Calibr has assembled a premier scientific team and developed an innovative cell therapy technology that can take us to the next frontier of cancer treatment,” says Mohit Trikha, Ph.D., VP and head of Oncology Early Development at AbbVie. “The combination of AbbVie’s oncology discovery and early development expertise and Calibr’s novel switchable CAR-T therapy platform aims to advance the current standard of care, with the potential rapidly advancing new treatment options for patients.”
Under the terms of the license agreement, AbbVie will pay Calibr an upfront license fee and gain exclusive access to Calibr’s switchable CAR-T platform for a term of up to four years. The two organizations will work together to develop T-cell therapies directed to solid tumor targets identified by AbbVie.
AbbVie additionally has the option to develop other cell therapies toward AbbVie-nominated targets and license existing Calibr cell therapy programs under development for hematological and solid cancers, including Calibr’s lead program. Calibr plans to enter this lead candidate into clinical studies for lymphoma during 2019.
In addition, the agreement provides AbbVie with an option to acquire an exclusive license to Calibr’s switchable CAR-T platform and programs within the first four years of the collaboration. The companies will share responsibility for preclinical development, with AbbVie responsible for clinical development and commercialization, and Calibr eligible to receive success-based milestone payments and royalties.
IN THE PIPELINE
AbbVie reported positive top-line results during April from the Phase III SELECT-COMPARE clinical trial showing that after 12 weeks, upadacitinib (15 milligrams, once-daily) met the primary endpoints of ACR20 and clinical remission versus placebo. All ranked secondary endpoints were also achieved versus either placebo or adalimumab (40 milligrams every other week). The ongoing study evaluates upadacitinib, an investigational oral JAK1-selective inhibitor, in patients with moderate to severe rheumatoid arthritis who are on a stable background of methotrexate and had an inadequate response.
“These results show a significant impact on both signs and symptoms and radiographic progression compared to placebo, as well as improvements in important measures such as ACR response and low disease activity compared to adalimumab,” Dr. Severino says. “We are excited by these strong results which add to the body of evidence that support the potential of upadacitinib to be an important treatment option for patients with rheumatoid arthritis.”
The study showed that at week 12, 71 percent of patients receiving an oral once-daily dose of upadacitinib 15 milligrams achieved an ACR20 response, compared with 36 percent of patients receiving placebo. A significantly higher proportion of patients receiving upadacitinib achieved clinical remission (based on Disease Activity 28 [DAS28] C-Reactive Protein [CRP]) compared with placebo at week 12 (29 percent versus 6 percent, respectively). Patients receiving upadacitinib achieved ACR50/70 responses of 45/25 percent compared to 15/5 percent of patients receiving placebo at week 12. Additionally low disease activity (LDA) based on DAS28 (CRP) was seen in 45 percent of patients receiving upadacitinib compared to 29 percent receiving adalimumab and 14 percent receiving placebo at week 12, respectively.
In June, FDA approved via priority review Venclexta (venetoclax tablets) in combination with rituximab for the treatment of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma – with or without 17p deletion – who have received at least one prior therapy.
The marketing approval was based on MURANO Phase III clinical trial data, which demonstrated a significant improvement in progression-free survival for relapsed/refractory (R/R) CLL patients, reducing the risk of disease progression or death by 81 percent when compared to bendamustine in combination with rituximab, a standard-of-care chemoimmunotherapy regimen.
Clinical trial patients who received Venclexta plus rituximab also achieved an overall response rate (ORR) of 92 percent and those who received the chemoimmunotherapy regimen achieved an ORR of 72 percent.
Venclexta plus rituximab is the first oral-based, chemotherapy-free combination in CLL that allows patients an option for fixed treatment duration. Venclexta has been granted four Breakthrough Therapy Designations (BTDs) by FDA, including for the combination treatment regimen of Venclexta plus rituximab for patients with R/R CLL. The approval of the Venclexta plus rituximab treatment regimen marks the second approval granted under priority review by FDA for Venclexta. Outside of the United States, regulatory submissions to and reviews with health authorities are underway.
FDA also approved expanding Venclexta’s indication as monotherapy for CLL or SLL patients, with or without 17p deletion, who have received one prior therapy. Previously, Venclexta, the first B-cell lymphoma-2 (BCL-2) inhibitor in CLL, was approved under accelerated approval in the United States in April 2016 as a monotherapy for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.
Additionally in June, AbbVie announced the presentation of investigational data from a new analysis of undetectable minimal residual disease (uMRD) rates from the pivotal Phase III MURANO trial of Venclexta in combination with rituximab (VenR) in patients with relapsed or refractory chronic lymphocytic leukemia. Of the 121 patients who achieved uMRD (meaning less than one CLL cell in 10,000 white blood cells were detectable using a standardized test) at the end of combination therapy (EOCT), 83 percent maintained uMRD and were progression-free for a median of 13.8 months (range, 5.6-23.0 months) thereafter. Venclexta is being developed by AbbVie and Roche. The medicine is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside the United States.
CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (type of white blood cells) are found predominantly in the blood and bone marrow. Undetectable minimal residual disease is an objective measure defined by the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment. Prospective clinical trials have suggested that achieving undetectable minimal residual disease, also known as MRD negativity (MRD-), may have a prognostic impact on response duration and survival outcomes.
Also in June, AbbVie presented new patient-reported outcome data from three Phase III trials evaluating upadacitinib in adult patients with moderate to severe rheumatoid arthritis. Improvements in pain, physical function and morning joint stiffness were reported after 12 weeks of treatment with upadacitinib (15 milligrams and 30 milligrams, once-daily) in SELECT-NEXT and SELECT-BEYOND and after 14 weeks of treatment in SELECT-MONOTHERAPY. Additionally, improvements were reported in fatigue and work instability in SELECT-NEXT and patients’ physical component of health-related quality of life in SELECT-NEXT and SELECT-BEYOND at 12 weeks. AbbVie had previously announced positive top-line results from SELECT-NEXT, SELECT-BEYOND and SELECT-MONOTHERAPY.
“Across three Phase III studies with different patient populations, patients treated with upadacitinib reported improvements in physical function, joint pain and morning stiffness,” says Marek Honczarenko, M.D., Ph.D., VP, immunology development, AbbVie. “These results show upadacitinib’s potential to address the challenges rheumatoid arthritis patients face when performing everyday activities.”
During that same month, the company announced positive top-line results from SELECT-EARLY showing that both doses of upadacitinib monotherapy (15 milligrams and 30 milligrams) met the primary endpoints of ACR50 at week 12 and clinical remission at week 24 versus methotrexate (MTX). Additionally, all ranked secondary endpoints were met. The ongoing study evaluates upadacitinib as a monotherapy treatment compared to methotrexate monotherapy in adult patients with moderate to severe rheumatoid arthritis who were methotrexate-naïve.
In July, FDA approved Orilissa (elagolix), the first oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for women with moderate to severe endometriosis pain. FDA regulators approved Orilissa under priority review.
Orilissa, developed jointly by AbbVie and Neurocrine Biosciences Inc., represents the first FDA-approved oral treatment for the management of moderate to severe pain associated with endometriosis in over a decade and was expected to be available in U.S. retail pharmacies in early August 2018.
“Orilissa represents a significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease,” Dr. Severino says. “The approval of Orilissa demonstrates AbbVie’s continued commitment to address serious diseases and unmet needs.”
Endometriosis is one of the most common gynecologic disorders in the United States. It affects an estimated one in 10 women of reproductive age and can be associated with pain symptoms that can be debilitating. Women can suffer for up to six to 10 years and visit multiple physicians before receiving a proper diagnosis.
Endometriosis-associated pain is often managed with medicines such as oral contraceptives, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and hormonal therapies, which can work for some women but very few are specifically indicated for the treatment of endometriosis.
In more extensive cases, surgical interventions (e.g., laparotomy, laparoscopy, or hysterectomy) are often pursued, and may not be curative for all individuals.
The marketing clearance of Orilissa was supported by clinical data from two replicate studies in the largest endometriosis Phase III trial program conducted to date, which evaluated nearly 1,700 women with moderate to severe endometriosis pain. Clinical trial data demonstrated that Orilissa significantly reduced the three most common types of endometriosis pain: daily menstrual pelvic pain, non-menstrual pelvic pain, and pain with sex. A higher proportion of women treated with Orilissa 150 milligrams once daily and 200 milligrams twice daily were responders for daily menstrual pain and non-menstrual pelvic pain compared to placebo in a dose-dependent manner at month three. Women were defined as responders if they experienced a reduction in daily menstrual pain and non-menstrual pelvic pain with no increase in analgesic use (nonsteroidal anti-inflammatory drug or opioid) for endometriosis-associated pain.
Both Orilissa treatment groups showed statistically significant greater mean decreases from baseline compared to placebo in daily menstrual pain and non-menstrual pelvic pain at month six. Women in the Phase III studies also provided a daily self-assessment of their endometriosis pain using a numeric rating scale (NRS) and women taking Orilissa 150 milligrams once daily and 200 milligrams twice daily reported a statistically significant reduction from baseline in NRS scores compared to placebo at month three. Clinical trial data also demonstrated women taking Orilissa 200 milligrams twice daily showed statistically significant greater reduction in pain with sex from baseline to month three compared to placebo.
Also in July, AbbVie announced the submission of a supplemental new drug application to FDA for Venclexta in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for treating newly diagnosed patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. The sNDA submission as based on investigational data from two studies: M14-358, a Phase Ib trial evaluating Venclexta in combination with an HMA (Venclexta or decitabine), and M14-387, a Phase I/II trial of Venclexta in combination with LDAC.
“AML is an especially lethal and aggressive form of blood cancer with limited advances in care in three decades and few treatment options for patients ineligible for intensive chemotherapy,” Dr. Severino says. “The data submitted to the FDA may potentially reshape how AML is treated. We look forward to working with the FDA and other health authorities during the review of these data.”
AML, primarily a disease of older patients, is the most common form of acute leukemia in adults, in which the bone marrow makes abnormal, immature types of white blood cells, red blood cells or platelets. AML is an aggressive blood cancer that, if left untreated, can progress quickly. In the United States, there will be an estimated 19,520 new cases and 10,670 deaths due to AML in 2018.
In addition to CLL and AML, Venclexta is being studied in a range of hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma and myelodysplastic syndrome (MDS). Together, partner developers AbbVie and Roche are committed to BCL-2 research with Venclexta, which is being evaluated in clinical trials for several types of hematologic cancers.
In August, AbbVie and partner developer Neurocrine announced results from the Phase III ELARIS UF-EXTEND extension study (MI2-816) showing at month 12 that Orilissa (300 mg twice daily), in combination with low-dose hormone (add-back) therapy (estradiol 1.0 milligrams/norethindrone acetate 0.5 milligrams), reduced heavy menstrual bleeding with 87.9 percent of women with uterine fibroids achieving clinical response.
This result was consistent with that observed in the two pivotal Phase III studies, ELARIS UF-I and ELARIS UF-II, in which 68.5 percent and 76.2 percent of women with uterine fibroids who received Orilissa with add-back therapy for six months achieved clinical response, respectively. Clinical response was defined as menstrual blood loss volume of less than 80 mL and a 50 percent or greater reduction in menstrual blood loss volume from baseline to their final month. Secondary endpoint results in the extension study were also consistent with that observed in the pivotal studies.
In September, AbbVie announced new results from the ongoing Phase IIb study including longer-term (32-week) efficacy and safety data and patient-reported outcomes data evaluating upadacitinib in adult patients with moderate-to-severe atopic dermatitis. Results from a pre-specified, interim analysis from the Phase IIb dose-ranging study showed that treatment with upadacitinib 7.5 milligrams, 15 milligrams, or 30 milligrams resulted in greater improvements in itch and skin lesions, with statistically significant differences observed versus placebo at week 32. Additionally, results from a further analysis of a subset of patients showed that upadacitinib improved patient-reported itch and impact on sleep due to atopic dermatitis in patients receiving upadacitinib (30 milligrams, once-daily) compared to placebo at week 16.
“Results from this study increase our understanding of upadacitinib’s potential to be an important treatment option for patients living with atopic dermatitis,” Dr. Honczarenko says. “At AbbVie, we continuously strive to discover and develop innovative medicines for patients who are in need of more treatment options that advance standards of care and improve quality of life. Data from the mid-stage clinical study support the recent advancement of upadacitinib into Phase III clinical studies and underscore our commitment to patients with atopic dermatitis.”
Atopic dermatitis is a common chronic, relapsing, inflammatory skin disease with associated comorbidities. One-third of atopic dermatitis patients have moderate-to-severe disease, which manifests as a debilitating, itchy rash with significant physical, psychological, and economic burdens. There is a large unmet need for therapies that are effective to manage the signs and symptoms of moderate to severe atopic dermatitis.
Also during September, AbbVie announced new patient-reported outcomes data from three pivotal Phase III trials evaluating risankizumab, an investigational interleukin-23 (IL-23) inhibitor, in adult patients with moderate-to-severe plaque psoriasis. Across three trials, patients reported significant improvements in health-related quality of life, mental health, and work productivity measures when treated with risankizumab. AbbVie submitted a biologics license application to FDA for risankizumab in April.
At week 16, significantly more risankizumab-treated patients reported a psoriasis symptom scale (PSS) score of 0, indicating they were symptom-free based on a score assessing pain, redness, and itchiness compared with Janssen’s Stelara (ustekinumab) and placebo in ultIMMa-1 and ultIMMa-2. Significantly more patients treated with risankizumab continued to report a PSS score of 0 at one year (52 weeks) compared to ustekinumab. In IMMvent, significantly more patients treated with risankizumab achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, indicating psoriasis no longer had impact on their life quality, compared to Humira (adalimumab) at week 16. Risankizumab-treated patients maintained reported outcomes at week 44 in IMMvent. Improvements in hospital anxiety and depression scales (HADS) and work limitation questionnaire (WLQ), a measure of work productivity, were also reported.
“Patients treated with risankizumab reported significant improvements in severity of psoriasis symptoms and measures of quality of life compared to current standards of care, as consistently demonstrated by the results of all three Phase III pivotal trials,” Dr. Honczarenko says. “Patients with psoriasis are seeking new treatment options that help them not only to achieve and maintain clear skin, but may also improve their quality of life. These results add to the growing body of evidence demonstrating that risankizumab has the potential to be an important additional treatment option for patients with plaque psoriasis.”
Also in September, FDA expanded the label for Venclexta in combination with rituximab to include information about patients with previously-treated chronic lymphocytic leukemia who achieved minimal residual disease-negativity in the Phase III MURANO trial.
MRD-negativity takes place when less than one CLL cell per 10,000 lymphocytes can be detected in the blood or bone marrow using sensitive analytical methods. More than half (53 percent) of patients treated with the Venclexta and rituximab combination achieved MRD-negativity (undetectable disease) after approximately nine months on therapy (three months after the last dose of rituximab), while 12 percent of patients treated with the standard chemoimmunotherapy regimen of bendamustine plus rituximab achieved MRD-negativity.
“With this label expansion for Venclexta, physicians now have additional information on MRD-negativity, which is becoming an increasingly important goal when caring for their previously-treated CLL patients,” Dr. Severino says. “Venclexta plus rituximab is the first chemotherapy-free combination for previously treated CLL that allows patients the ability to stop treatment after approximately two years. This label expansion is another important milestone in our efforts to advance care for patients with difficult-to-treat blood cancers.”