AbbVie: Welcome Back
Just a few years after its spin-off from Abbott, Med Ad News Company of the Year AbbVie is very much back in the big pharma conversation.
AbbVie Inc.
1 North Waukegan Road
North Chicago, IL 60064
847-932-7900
Website: abbvie.com
Best-Selling Products
Product | 2015 Sales | 2014 Sales |
---|---|---|
Humira |
$14,012 |
$12,543 |
Viekira | $1,639 | $48 |
Lupron | $826 | $778 |
Synthroid | $755 | $709 |
Imbruvica | $754 | — |
Synagis | $740 | $835 |
Kaletra | $700 | $870 |
AndroGel | $694 | $934 |
Creon | $632 | $516 |
All sales are in millions of dollars.
Financial Performance
2015 | 2014 | |
---|---|---|
Revenue | $22,859 | $19,960 |
Net income | $5,144 | $1,774 |
Diluted EPS | $3.13 | $1.10 |
R&D expense | $4,285 | $3,297 |
1H16 | 1H15 | |
---|---|---|
Revenue |
$12,410 |
$10,515 |
Net income | $2,964 | $2,388 |
Diluted EPS | $1.81 | $1.47 |
R&D expense | $2,070 | $1,792 |
In millions of dollars, except EPS
Just three and a half years after it was born out of a spin-off from Abbott Laboratories, AbbVie has clearly established itself as a big pharma heavy hitter in its own right. The young company’s flagship product, Humira, was the world’s leading pharmaceutical brand by sales for the fourth consecutive year in 2015, and looks likely to retain its title for a few more years at the least. Its newest blockbuster, the hepatitis C drug Viekira, passed the billion-dollar sales mark with plenty of room to spare in its first full year on the market and is continuing to grow impressively in 2016. And its most significant M&A transaction, the acquisition of Pharmacyclics in May 2015, is looking very smart, as Imbruvica will likely blow past the billion-dollar mark this year. All this plus a solid pipeline, double-digit top-line growth in 2015 and the first half of 2016, and a rapidly improving bottom line during what has been a stagnant time for many of pharma’s biggest companies has earned AbbVie its selection as Med Ad News Company of the Year. Not bad for a company younger than most kindergarteners.
“In just three years, AbbVie has become a leading biopharmaceutical company with top-tier business performance, financial results, and return to shareholders, with compound annual growth in revenues of more than 10 percent and EPS growth of approximately 17 percent since inception,” says Richard Gonzalez, the company’s chairman and CEO. “AbbVie’s total shareholder return of 92 percent over this period is also in the top of our peer group. AbbVie is delivering on our initial promise to shareholders – to be an innovation-driven, patient-focused specialty biopharmaceutical company that delivers top-tier financial performance and brings a stream of innovative therapies to the market. Our performance and ability to execute, as demonstrated in our first three years as an independent company, gives us great confidence in our future.”
AbbVie’s total top-line revenue during 2015 amounted to $22.86 billion, an improvement of 14.5 percent compared with the previous year. Net income nearly tripled, from $1.77 billion to $5.14 billion, and diluted earnings per share also nearly tripled, from $1.10 to $3.13. According to company leadership, this was primarily due to the continued growth of Humira worldwide, the launch of the hepatitis C treatment Viekira, and post-Pharmacyclics acquisition revenue from Imbruvica. During the first half of 2016, top-line revenue rose another 18 percent to $12.41 billion, while net income was up 24.1 percent to $2.96 billion and diluted earnings per share rose 34 cents to $1.81, again thanks largely to Humira, Viekira, and Imbruvica. AbbVie executives have projected full-year 2016 earnings per share landing between $3.82 and $3.92.
Product Performance
Leading AbbVie’s sales charts, and everyone else’s, during 2015, the autoimmune product Humira rolled up $14.01 billion in sales for the year, an improvement of 11.7 percent. Humira has now been the world’s top-selling prescription drug for four years running, and five is looking likely; during the first half of 2016, the product’s sales totalled $7.73 billion, up 16.2 percent from the first half of 2015. Consensus worldwide peak sales of $18.8 billion have been projected for Humira in 2018.
In June, FDA approved Humira for the treatment of non-infectious intermediate, posterior and panuveitis. Humira is now the first FDA-approved non-corticosteroid therapy available for adults with non-infectious intermediate, posterior and panuveitis. This approval marked the 10th approved indication for Humira in the United States for immune-mediated diseases. That same month, the European Commission also approved Humira for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate.
“We are pleased to provide patients with the first FDA-approved non-corticosteroid treatment option for certain types of uveitis, an eye disease that can flare and impact vision,” says Michael Severino, M.D., executive VP, R&D and chief scientific officer, AbbVie. “These approvals reflect our ongoing focus on continuing to innovate with Humira to address critical unmet needs of patients living with serious immune-mediated diseases.”
Prior to this approval, ophthalmologists and rheumatologists had no FDA-approved treatment options other than corticosteroids. Humira targets and helps block TNF-α, a specific source of inflammation that can have a role in uveitis. The FDA approval is based on results from two pivotal Phase III studies, VISUAL-I and VISUAL-II, which demonstrated that adult patients with active and controlled non-infectious intermediate, posterior and panuveitis treated with Humira had a significantly lower risk for treatment failure (a combination of uveitic flare and decrease in visual acuity), compared to placebo.
Coming in second among AbbVie drugs in 2015 was a new entry, the hepatitis C product Viekira Pak, which earned $1.64 billion in sales for the year after being approved in December 2014. Viekira Pak is an all-oral, interferon-free treatment, with or without ribavirin indicated for the treatment of patients with chronic genotype 1 hepatitis C virus infection, including those with compensated cirrhosis. As of its launch, it was the only FDA-approved regimen containing three distinct mechanisms of action – a NS5A inhibitor, a NS3/4A protease inhibitor, and a non-nucleoside NS5B polymerase inhibitor – that work together to attack the virus at three separate stages of the disease lifecycle to inhibit it from reproducing. In the first half of 2016, Viekira Pak sales were $833 million, an improvement of 35.4 percent over the first half of 2015.
During April, FDA approved a supplemental NDA for the use of Viekira Pak without ribavirin in patients with genotype 1b chronic hepatitis C virus infection and compensated cirrhosis (Child-Pugh A). The application had been previously granted priority review status by FDA, a designation given to investigational therapies that treat a serious condition and provide a significant improvement in safety or effectiveness.
“We are constantly striving to advance clinical care for patients living with chronic hepatitis C,” Dr. Severino says. “This approval is especially significant because patients with chronic HCV with compensated cirrhosis are among the tough to treat, and in our study Viekira PAK demonstrated 100 percent cure rates in GT1b patients without the use of ribavirin.”
The TURQUOISE-III study included in the sNDA evaluated the use of Viekira Pak without RBV for 12 weeks in GT1b patients with compensated cirrhosis (Child-Pugh A). Results demonstrated 100 percent sustained virologic response at 12 weeks post-treatment. No patients discontinued treatment due to adverse events.
In July, FDA approved Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets. Viekira XR is a once-daily, extended-release co-formulation of the active ingredients in Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and is for the treatment of patients with chronic genotype 1 hepatitis C virus infection, including those with compensated cirrhosis (Child-Pugh A).
Viekira XR is the first co-formulated three direct-acting antiviral treatment for adult patients with GT1 HCV. Viekira XR is given once-daily as three oral tablets and must be taken with a meal. It is used without ribavirin in GT1b patients and in combination with twice daily RBV in GT1a patients. The approval is supported by Phase III clinical trials for Viekira Pak which include data that demonstrated 100 percent sustained virologic response 12 weeks following treatment in GT1b patients with 12 weeks of therapy without ribavirin and 95 percent SVR in GT1a patients when used with ribavirin for 12 or 24 weeks of therapy.
Lupron placed third among AbbVie products in 2015 with sales of $826 million, up 6.2 percent compared with the previous year. In the first half of 2016, Lupron sales rose another 4.9 percent to $409 million. Lupron is indicated for the palliative treatment of advanced prostate cancer, treatment of endometriosis and central precocious puberty, and for the preoperative treatment of patients with anemia caused by uterine fibroids.
The hypothyroidism drug Synthroid was fourth in AbbVie’s product portfolio in 2015 with sales of $755 million, up 6.5 percent from the previous year. In the first half of 2016, Synthroid sales dropped 0.7 percent to $370 million.
The acquisition of Pharmacyclics Inc. during May 2015 brought the oncology drug Imbruvica into the AbbVie fold; for the remainder of that year, Imbruvica generated $754 million in sales for the company. The product has already more than matched that total in 2016, with $820 million in sales in the first two quarters. As of its acquisition, Imbruvica was approved by FDA for four indications: for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy; for the treatment of patients with chronic lymphocytic leukemia who have received at least one prior therapy; for the treatment of CLL patients with deletion of the short arm chromosome 17; and for the treatment of patients with Waldenstrom’s macroglobulinemia.
In March, FDA approved Imbruvica as a first-line treatment for patients with chronic lymphocytic leukemia. The approval was based on data from the randomized, multi-center, open-label Phase III RESONATE-2 (PCYC-1115) trial, which evaluated the use of Imbruvica versus chlorambucil in 269 treatment-naïve patients with CLL or small lymphocytic lymphoma aged 65 years or older.
“This approval represents a significant leap forward for patients diagnosed with CLL who may want to consider an alternative first-line treatment to traditional chemotherapy,” Dr. Severino says. “AbbVie is committed to making significant improvements in the lives of patients with hematologic malignancies and will continue to explore ways to improve treatment options for patients.”
The prevalence of CLL is about 115,000 patients in the United States, with approximately 15,000 newly diagnosed patients every year. CLL is a disease of elderly patients, with an average diagnosis age of 71. Imbruvica significantly prolonged progression-free survival as determined by an Independent Review Committee, reducing the risk of progression or death by 84 percent versus chlorambucil. Imbruvica was also associated with a significantly higher IRC-assessed overall response rate versus chlorambucil.
In May, FDA updated the Imbruvica Prescribing Information to include new data from two Phase III trials supporting its expanded use in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. The label now includes overall survival results in previously untreated CLL/SLL patients from the Phase III RESONATE-2 (PCYC-1115) trial. The Imbruvica label has also been updated with safety and efficacy data from the Phase III HELIOS (CLL3001) trial assessing the use of Imbruvica in combination with bendamustine and rituximab versus placebo plus BR in relapsed/refractory patients with CLL/SLL. Additionally, following a review of the November 2015 sNDA, FDA approved a new Imbruvica indication to include the treatment of patients with SLL with or without the deletion of chromosome 17p.
Synagis, indicated for the prevention of respiratory syncytial virus infection in high risk infants, earned $740 million in sales for AbbVie in 2015, down 11.4 percent from the previous year. According to company executives, the drop was due to a less severe RSV season. In the first half of 2016, Synagis sales were down another 4.4 percent to $364 million.
Sales of the HIV product Kaletra dropped 19.5 percent to $700 million in 2015, which company executives blamed on growing competition in the HIV space. In the first half of 2016, Kaletra sales fell another 19.5 percent to $279 million.
The testosterone replacement therapy AndroGel lost more than a quarter of its sales in 2015, falling from $934 million to $694 million due to new generic competition for its 1% formulation and an overall decline in the market. AndroGel sales edged up 1.5 percent in the first half of 2016 to $327 million.
Creon, indicated for exocrine pancreatic insufficiency, enjoyed a nice sales bounce in 2015, up 22.5 percent to $632 million due to continued market growth and higher market share. In the first half of 2016, Creon sales rose another 15.2 percent to $330 million.
Acquisitions & Collaborations
During January, AbbVie and the immunotherapy platform at The University of Texas MD Anderson Cancer Center announced a collaboration to find new ways to unleash the immune system’s potential to fight cancer. According to company leaders, the three-year collaboration agreement provides a framework for MD Anderson and AbbVie to efficiently choose and carry out preclinical and clinical studies evaluating new ideas in the cutting-edge area of immuno-oncology.
“Pairing MD Anderson’s cutting-edge preclinical, translational and clinical capabilities with AbbVie’s innovative discovery and development programs accelerates our ability to deliver new therapies that can help transform the lives of people affected by cancer,” Dr. Severino says. “AbbVie is pleased to partner with MD Anderson’s world-class experts so that together we can advance the science of cancer immunotherapy for the benefit of patients around the world.”
AbbVie and MD Anderson each assigned two scientists to a joint scientific committee, which decides on projects to pursue. The collaboration got underway with projects driven by AbbVie Biotherapeutics, AbbVie’s center of innovation in the biotech hub of the San Francisco Bay Area. Future projects will draw from the extensive portfolio of oncology programs across the AbbVie Oncology pipeline.
During March, AbbVie and Boehringer Ingelheim announced a global collaboration to develop and commercialize BI 655066, an anti-IL-23 monoclonal biologic antibody in Phase III development for psoriasis. AbbVie and Boehringer Ingelheim also are evaluating the potential of this biologic therapy in Crohn’s disease, psoriatic arthritis, and asthma. In addition to the anti-IL-23 antibody, AbbVie gained rights to an anti-CD-40 antibody, BI 655064, in Phase I development. Boehringer Ingelheim will retain responsibility for further development of BI 655064, and AbbVie may elect to advance the program after completion of certain undisclosed clinical achievements.
“This collaboration positions BI 655066 as AbbVie’s lead investigational compound in psoriasis, complementing our robust immunology pipeline,” Dr. Severino says. “Our expertise in developing and commercializing the world’s leading biologic, combined with Boehringer Ingelheim’s clinical success to date will enable us to offer patients a new treatment option with the potential to meaningfully improve the standard of care.”
Recent Phase II head-to-head study results in patients with moderate-to-severe plaque psoriasis showed that BI 655066 had greater efficacy over Stelara, a commonly used treatment for the condition. After nine months, 69 percent of patients with moderate-to-severe plaque psoriasis maintained clear or almost clear skin with BI 655066 in the higher dose group compared to 30 percent of patients on Stelara. Patients also achieved this skin clearance faster (about eight weeks versus about 16 weeks) and for more than two months longer (32 weeks versus 24 weeks) than those on Stelara. In addition, completely clear skin was maintained after nine months in nearly triple the percentage of patients on BI 655066 compared with Stelara (43 percent versus 15 percent). BI 655066 is in Phase II development for Crohn’s disease and asthma and is about to enter Phase II development for psoriatic arthritis. In addition, Phase II data for Crohn’s disease was to be presented at an upcoming medical meeting.
Under the terms of the license agreement, AbbVie made an initial upfront payment of $595 million. Boehringer Ingelheim is eligible to receive additional development and regulatory milestone payments and royalties on net sales, the terms of which are not disclosed. In the initial period, the companies are sharing the responsibility for future development of BI 655066. AbbVie is solely responsible for commercialization of BI 655066, while Boehringer Ingelheim retains an option to co-promote the compound in asthma. The companies will also establish a joint steering committee for the development as well as the initial commercialization phase.
In February, AbbVie and Synlogic announced the signing of a multi-year global R&D collaboration. The collaboration is focused on developing novel medicines for the treatment of inflammatory bowel disease using Synlogic’s proprietary approach for a new class of synthetic biotic medicines that power the microbiome.
Under the terms of the collaboration, Synlogic will discover, characterize, and optimize synthetic biotics-based drug candidates through an R&D program covering a limited number of effectors modulating the IBD pathophysiology, with special emphasis on Crohn’s disease and ulcerative colitis. One of the goals of the multi-year collaboration is to combine AbbVie’s expertise in metabolic and inflammatory diseases with Synlogic’s platform to generate and advance to the clinic a novel, oral probiotic therapeutic candidate. Using Synlogic’s synthetic biotics platform, the novel probiotic drug candidate will be designed with synthetic programmable genetic circuits that can blend with the patient’s microbiome and perform a programmed therapeutic operation involved in the IBD disease process acheter cialis sans ordonnance. AbbVie and Synlogic will evaluate synthetic biotic candidates that modulate certain effectors involved in the IBD pathway and advance them through preclinical development, with AbbVie being responsible for regulatory filings, clinical development and worldwide marketing of any resulting products. Financial terms were not disclosed.
“Synlogic’s innovative approach to targeting the microbiome offers a new way to address inflammatory bowel disease,” says Jim Sullivan, VP, pharmaceutical discovery, AbbVie. “AbbVie is committed to collaborating with scientific leaders with new technologies and therapeutic advances that complement AbbVie’s internal expertise and share our commitment to advancing the standard of care for patients.”
In April, AbbVie and Argenx, a clinical-stage biopharmaceutical company focused on creating and developing differentiated therapeutic antibodies to treat cancer and severe autoimmune diseases, announced a collaboration to develop and commercialize ARGX-115. ARGX-115 is Argenx’s preclinical-stage human antibody program targeting the novel immuno-oncology target GARP, a protein believed to contribute to immuno-suppressive effects of T-cells.
“The ability to modulate the body’s own immune system to fight cancer is one of the most promising scientific advancements over the past decade,” says Anil Singhal, VP, Early Oncology Development, AbbVie. “We believe that the ARGX-115 program is a unique opportunity to explore the potential to block certain immune-suppressive pathways that allow cancers to grow.”
Under the terms of the agreement, Argenx is conducting research and development through IND-enabling studies. Upon successful completion of these studies, AbbVie may exercise an exclusive option to license the ARGX-115 program and assume responsibility for further clinical development and commercialization. Argenx received an upfront payment of $40 million from AbbVie for the exclusive option to license ARGX-115 and near-term preclinical milestones of $20 million. Argenx is also eligible to receive additional development, regulatory and commercial payments up to $625 million upon achievement of pre-determined milestones as well as tiered, up to double-digit royalties on net sales upon commercialization. Argenx has the right to co-promote ARGX-115-based products in the European Union and Swiss Economic Area and combine the product with its own future immuno-oncology programs. Should AbbVie not exercise its option to license ARGX-115, Argenx retains the right to pursue development of ARGX-115 alone.
In addition to the ARGX-115 program, and upon reaching a predetermined preclinical stage milestone, AbbVie will fund further GARP-related research by Argenx for an initial period of two years. AbbVie will have the right to license additional therapeutic programs emerging from this research, for which Argenx could receive associated milestone and royalty payments.
Also in April, AbbVie and CytomX Therapeutics Inc. announced a collaboration to co-develop and co-commercialize Probody Drug Conjugates against CD71, also known as transferrin receptor 1 (TfR1). CD71 is highly expressed in a number of solid and hematologic cancers and has attractive molecular properties for efficient delivery of cytotoxic payloads to tumor cells. Probody therapeutics are designed to take advantage of unique conditions in the tumor microenvironment to enhance the tumor-targeting features of an antibody and reduce drug activity in healthy tissues.
“We believe that the Probody platform provides a differentiated opportunity to combine with our strength in antibody drug conjugates,” says Steve Davidsen, Ph.D., VP of oncology drug discovery at AbbVie. “We are encouraged by the promising preclinical data that CytomX has generated for their Probody drug conjugate programs to date and look forward to working closely with their team. This collaboration will enable us to expand our innovative pipeline in antibody drug conjugates and leverage our strength in that area to previously unexplored targets.”
Probody therapeutics are designed to remain inactive until they are activated by proteases in the tumor microenvironment. As a result, Probody therapeutics bind selectively to tumors and avoid binding to healthy tissue, to minimize toxicity and potentially create safer, more effective therapies. CytomX has generated preclinical data that demonstrates that Probody drug conjugates can safely and effectively target tumor antigens, such as CD71, that are not addressable by conventional antibody-drug conjugates.
Under the terms of the agreement, CytomX and AbbVie will co-develop a Probody drug conjugate against CD71, with CytomX leading pre-clinical and early clinical development. AbbVie will lead later development and commercialization, with global late-stage development costs shared between the two companies.
CytomX receives an upfront payment of $30 million and is eligible to receive up to $470 million in development, regulatory, and commercial milestones, pending the achievement of pre-determined outcomes. AbbVie will lead global commercial activities with CytomX eligible to receive a profit share in the United States and tiered double-digit royalties on net product sales outside of the U.S. CytomX retains an option to co-promote in the United States. AbbVie also receives exclusive worldwide rights to develop and commercialize Probody drug conjugates against up to two additional, undisclosed targets. Should AbbVie ultimately pursue these targets, CytomX is eligible to receive additional milestone and royalty payments per target on any resulting products.
Also in April, AbbVie announced that it would acquire Stemcentrx and its lead late-stage asset rovalpituzumab tesirine (Rova-T), currently in registrational trials for small cell lung cancer. Rova-T is a novel biomarker-specific therapy that is derived from cancer stem cells and targets delta-like protein 3 (DLL3) that is expressed in more than 80 percent of SCLC patient tumors and is not present in healthy tissue. Registrational trials for third-line small cell lung cancer are expected to complete enrollment by the end of 2016.
“AbbVie is committed to continued innovation in oncology, a critical component of our long-term growth and an area of significant need to millions of patients worldwide,” Gonzalez says. “The addition of Stemcentrx and its late-stage compound Rova-T provide AbbVie with a unique platform in solid tumor therapeutics and complement our leadership position in hematologic oncology. We believe the acquisition of Stemcentrx will strengthen and accelerate our ability to deliver innovative therapies that will have a remarkable impact on patients’ lives.”
In Phase I/II studies of relapsed SCLC patients who have previously failed one or more standard therapies, Rova-T demonstrated overall response rates of 44 percent in the patients identified with high expression of DLL3. The expression of DLL3 suggests Rova-T also may be useful across multiple tumor types, including metastatic melanoma, glioblastoma multiforme, prostate, pancreatic and colorectal cancers, where DLL3 expression ranges from 50-80 percent. Rova-T combines a targeted antibody that delivers a cytotoxic agent directly to the DLL3-expressing cancer cells while minimizing toxicity to healthy cells.
Rova-T is under investigation as a third-line treatment in SCLC, where no currently approved therapy exists. Rova-T also has been submitted to the FDA for Breakthrough Therapy designation.
Beyond Rova-T, Stemcentrx has four novel compounds in clinical trials across several solid tumor indications including triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer. Stemcentrx has additional pre-clinical compounds advancing toward clinical trials in 2016 and a proprietary technology platform that leverages stem cell biology to identify and screen potential targets against live tumor tissue to more predictably advance discovery and development of new assets.
Also in April, AbbVie and the University of Chicago entered into a five-year collaboration agreement designed to improve the pace of discovery and advance medical research in oncology at both organizations. The joint strategic research agreement is designed to encourage and strengthen collaboration among researchers. Initially, both organizations will work together to advance research in several areas of oncology, which could include, among others, breast, lung, prostate, colorectal and hematological cancer. Research projects are chosen by a joint steering committee, comprising representatives from each organization. AbbVie also gains an option for an exclusive license to certain University of Chicago discoveries made under the agreement.
As part of the agreement, AbbVie will provide funding for the collaboration that may be used for purposes including preclinical research, clinical trials and possible future programs at the University resulting from this partnership. The overall collaborative efforts will provide University of Chicago physicians and scientists with the opportunity to participate in AbbVie-sponsored clinical trials, access to new therapies developed by AbbVie for use in preclinical research funded under the collaboration, as well as opportunities to work closely with AbbVie’s research and development teams to promote scientific knowledge exchange.
“Advancements in oncology – both at the basic science and clinical levels – are happening faster and more broadly every day,” says Gary Gordon, M.D., Ph.D., VP, oncology clinical development, AbbVie. “Collaborating closely with the scientists and clinicians at the University of Chicago allows us to expand our own research efforts even further to benefit patients.”
As part of the collaborative agreement, researchers from the University of Chicago and AbbVie will participate in an annual symposium that brings together scientists from both institutions to discuss research and evaluate potential new projects.
In July, AbbVie and Bristol-Myers Squibb announced a clinical trial collaboration to evaluate the safety, tolerability, and efficacy of AbbVie’s recently acquired investigational biomarker-specific antibody drug conjugate Rova-T in combination with Bristol-Myers Squibb’s Opdivo and Opdivo + Yervoy regimen as a treatment for relapsed extensive-stage small cell lung cancer. The Phase I/II clinical program will explore the potential of combining Bristol-Myers Squibb’s immuno-oncology agents, which are designed to alleviate immune suppression, in conjunction with AbbVie’s investigational antibody drug conjugate, Rova-T, to drive improved and sustained efficacy and tolerability above the current standard of care. Rova-T is a novel antibody drug conjugate that targets and eliminates tumor initiating cells and other bulk tumor cells. This collaboration will determine if the targeted cell killing and antigen release caused by Rova-T may further enhance the effect of immunotherapy.
“We believe the combination of these cancer-fighting agents may offer patients a new treatment option in a disease with limited therapies,” says Scott J. Dylla, Ph.D., VP, research and development, AbbVie. “By combining immune-checkpoint inhibitors that prime the body’s immune system to fight cancer cells with Rova-T’s approach to target cancer stem cells, we hope to build on our goal to develop differentiated treatments with therapeutic benefit that elevate the standard of care for small cell lung cancer patients.”
Small cell lung cancer is a difficult-to-treat form of cancer that accounts for about 15 percent of all lung cancers. The five-year survival rate for extensive stage SCLC is less than 5 percent and treatment options are limited for the more than 234,000 people diagnosed annually.
Rova-T is a novel biomarker-specific therapy that targets cancer stem cells and combines a targeted antibody that delivers a cytotoxic agent directly to cancer cells expressing a delta-like protein 3 (DLL3). DLL3 is expressed in more than 80 percent of SCLC patient tumors and is not present in healthy tissue. Rova-T is currently in investigational studies as a third-line treatment for SCLC. AbbVie will initiate a first-line clinical study for Rova-T in SCLC and several other types of tumors in the near term.
Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and has regulatory approval in at least 54 countries including the United States, Japan, and in the European Union. Yervoy is a CTLA-4 immune checkpoint inhibitor approved for marketing in 50 countries globally for patients with unresectable or metastatic melanoma.
Recent Approvals/In The Pipeline
In January, AbbVie announced the initiation of six global Phase III clinical studies evaluating the safety and efficacy of its all-oral, once-daily, ribavirin-free investigational hepatitis C virus regimen, ABT-493, an NS3/4A protease inhibitor, and ABT-530, an NS5A inhibitor, in patients with genotypes 1-6 chronic HCV infection.
“We believe AbbVie’s work in hepatitis C has contributed to the transformation of HCV care over the last few years,” Dr. Severino says. “Our journey continues with the initiation of these Phase III studies, which we hope will help us meet the needs of an even broader range of patients living with hepatitis C.”
The ENDURANCE and EXPEDITION studies are part of AbbVie’s Phase III HCV pipeline program and will recruit approximately 1,600 patients globally, from over 250 study sites and in 27 countries. The primary efficacy endpoint of all six studies is rate of sustained virologic response at 12 weeks post-treatment.
The four ENDURANCE studies evaluate AbbVie’s investigational regimen in patients without cirrhosis for up to 12 weeks. ENDURANCE-1 compares SVR in GT1 chronic HCV infected patients who received ABT-493/ABT-530 treatment durations of 12 weeks and as short as eight weeks. ENDURANCE-2 evaluates AbbVie’s investigational regimen versus placebo in GT2 chronic HCV infected patients. ENDURANCE-3 compares AbbVie’s investigational regimen with sofosbuvir/daclatasvir in treatment-naïve patients with GT3 chronic HCV infection. ENDURANCE-4 evaluates GT4-6 chronic HCV infected patients.
The EXPEDITION trials evaluate AbbVie’s investigational regimen for 12 weeks in difficult to treat patient populations with chronic HCV infection. EXPEDITION-1 evaluates AbbVie’s investigational regimen in GT1, 2, 4-6 chronic HCV infected patients with compensated cirrhosis (Child-Pugh A). EXPEDITION-4 evaluates GT1-6 chronic HCV infected patients with severe renal impairment and end-stage renal disease, with or without compensated cirrhosis.
That same month, the company announced the start of a large Phase III clinical trial program to study the use of ABT-494, an investigational, once-daily, oral selective JAK1 inhibitor for the treatment of rheumatoid arthritis. This program will include adult patients with inadequate responses to conventional or biologic disease-modifying antirheumatic drugs, as well as methotrexate-naive patients.
“We continue to leverage our expertise in rheumatology and immunology to address the unmet needs of patients living with immune-mediated diseases, including those that fail to respond to the current standard of care,” says Scott Brun, M.D., VP, pharmaceutical development, AbbVie. “We are optimistic that our robust Phase III clinical trial program, which dosed the first patient in December, will help us further understand the therapeutic potential of ABT-494 across multiple patient populations and achieve our goal of providing patients with best-in-class treatment options.”
Data from the Phase II ABT-494 clinical trials, BALANCE-I and BALANCE-2, announced in September 2015, demonstrated the efficacy of the compound across 6, 12, and 18 milligram doses twice-daily, and 24 milligram once-daily in RA patients with an inadequate response to prior anti-tumor necrosis factor or methotrexate treatment.
The first two of the five Phase III ABT-494 clinical trials had already opened for enrollment in January in the United States. One study will evaluate ABT-494 in combination with MTX in adult patients with moderate to severely active RA who have had an inadequate response to prior treatment with MTX, and will include Humira as an active comparator. The second study will include patients who have had an inadequate response or intolerance to conventional synthetic DMARDs. These studies will include assessments of safety and tolerability, as well as key measures of efficacy including ACR responses and levels of disease activity. The other three Phase III clinical trials were scheduled to begin enrollment in early 2016 and will include patients with an inadequate response to biologics and patients who are MTX-naive.
Also in January, AbbVie and partner developer Neurocrine Biosciences Inc. announced the initiation of the first of two planned Phase III clinical studies evaluating the safety and efficacy of Elagolix alone or in combination with add-back therapy compared to placebo. These studies are designed to assess the change in menstrual blood loss utilizing the alkaline hematin method, comparing baseline to month six of treatment. Additional secondary efficacy endpoints are being evaluated; including assessing changes in fibroid volume, monthly blood loss, and hemoglobin levels. Bone mineral density will also be assessed.
“There are limited, non-surgical treatment options for women suffering from heavy menstrual bleeding associated with uterine fibroids,” Dr. Severino says. “AbbVie is eager to further explore Elagolix’s potential to address this unmet need.”
In February, the partners announced positive top-line results from the second of two replicate pivotal Phase III clinical trials evaluating the efficacy and safety of Elagolix in premenopausal women who suffer pain from endometriosis. Trial results show that after six months of continuous treatment, both doses of Elagolix (150 milligrams once daily and 200 milligrams twice daily) met the study’s co-primary endpoints. Elagolix reduced scores of menstrual pain (dysmenorrhea) and non-menstrual pelvic pain associated with endometriosis, at month three and month six, as measured by the Daily Assessment of Endometriosis Pain scale. Responder rates for the co-primary endpoints from this second Phase III pivotal study are consistent with results from the first Phase III pivotal study.
“Endometriosis affects an estimated 176 million women worldwide,” Dr. Severino says. “Patients voice their frustration about the need for more treatment options to medically manage endometriosis and its often debilitating pain. In an effort to address this need, AbbVie conducted the largest clinical trials in endometriosis to date. We are pleased with the outcomes of the pivotal trials thus far. AbbVie will continue to pursue Elagolix as a potential new treatment for the disease’s most common symptoms, including pain related to menstruation and chronic pelvic pain throughout the menstrual cycle.”
In April, FDA granted accelerated approval of Venclexta (venetoclax) tablets for patients diagnosed with chronic lymphocytic leukemia with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. FDA approved this indication under accelerated approval based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial. FDA approved Venclexta as a first-in-class, oral, once-daily medicine that selectively inhibits the BCL-2 protein. The BCL-2 protein blocks apoptosis (programmed cell death) of cells, including some cancer cells, and can be overexpressed in CLL cells. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. The drug is marketed collaboratively by the companies in the United States and by AbbVie outside of the United States.
“The FDA’s approval of Venclexta marks a major milestone for our company, and more importantly for the patients diagnosed with relapsed/refractory CLL who harbor the 17p deletion,” Gonzalez says. “BCL-2 inhibition is a novel mechanism which brings a new treatment option to patients who need additional therapies.”
In May, results from a Phase II trial showed that risankizumab, formerly BI 655066, was more effective than placebo in patients with moderately-to-severely active Crohn’s disease. These interim results are the first to be reported in this indication with risankizumab, which selectively blocks IL-23 through the specific targeting of the IL-23p19 subunit. After 12 weeks, 24 percent and 37 percent of patients achieved clinical remission (no symptoms or very mild symptoms of disease) with 200 milligrams and 600 milligrams risankizumab, respectively, compared with 15 percent of patients receiving placebo. Endoscopic remission (normalization of the lining of bowel as seen during an endoscopy) was achieved by 15 percent and 20 percent of patients receiving 200 milligrams and 600 milligrams risankizumab, respectively, compared with three percent of patients receiving placebo. Risankizumab also achieved higher rates of clinical response (defined by a Crohn’s Disease Activity Index of <150 or a reduction from baseline of at least 100 points) than placebo with nearly twice as many patients achieving a clinical response with risankizumab (37 percent and 42 percent in the 200 milligrams and 600 milligrams groups, respectively) compared with the placebo group (21 percent) at Week 12.
That same month, FDA approved Zinbryta (daclizumab), a new once-monthly, self-administered, subcutaneous treatment for relapsing forms of multiple sclerosis. The FDA approval of Zinbryta was primarily based on results from two clinical trials, including DECIDE, the largest and longest head-to-head Phase III clinical trial ever conducted in MS. The Phase IIb SELECT and Phase III DECIDE studies were global, randomized, double-blind, controlled studies that involved about 2,400 people living with RMS. Some patients in DECIDE were treated for up to three years. In DECIDE and SELECT, Zinbryta significantly reduced the annualized relapse rate, the primary endpoint of the studies, by 45 percent compared to Avonex up to 144 weeks and by 54 percent compared to placebo at 52 weeks, respectively. Zinbryta was developed jointly by AbbVie and Biogen.
“MS patients are in need of therapeutic choices to help manage their disease and Zinbryta is an important new option for patients,” Dr. Severino says. “AbbVie is committed to making a remarkable impact on the lives of patients, including in MS where there are particular unmet needs.”