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AbbVie Reports Full-Year 2015 and Fourth-Quarter Financial Results

On January 29, 2016 AbbVie (NYSE: ABBV) reported financial results for the fourth quarter and full year ended Dec. 31, 2015 (Press release, AbbVie, JAN 29, 2016, View Source;p=RssLanding&cat=news&id=2133541 [SID:1234508903]).

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"AbbVie delivered strong performance in 2015, exceeding original sales, margin expansion, and earnings projections for the year," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "We achieved significant growth in 2015, and expect to continue building on that momentum in 2016 with another year of strong performance."

Fourth-Quarter Results

Worldwide adjusted net revenues were $6.360 billion in the fourth-quarter, up 18.4 percent. On an operational basis, adjusted net revenues increased 24.4 percent, excluding a 6.0 percent unfavorable impact from foreign exchange rate fluctuations.

Global HUMIRA sales increased 16.0 percent on an operational basis, excluding the impact of foreign exchange. Exceptional U.S. HUMIRA growth of 20.7 percent was driven by continued momentum across all three major market categories – rheumatology, dermatology and gastroenterology. International HUMIRA sales growth was also strong in the fourth quarter, up 9.7 percent on an operational basis. Reported international HUMIRA sales growth in the quarter was reduced by 13.1 percent due to unfavorable foreign exchange.

Fourth-quarter global IMBRUVICA net revenue was $343 million, with U.S. sales of $295 million and international profit sharing of $48 million for the quarter.

Total company revenue growth was also driven by $554 million in global VIEKIRA sales in the quarter, as well as strong operational growth from Duodopa, Creon and Lupron.

Adjusted gross margin ratio in the fourth quarter was 80.5 percent, excluding intangible asset amortization and other specified items. On a GAAP basis, the gross margin ratio was 77.0 percent.

Adjusted selling, general and administrative (SG&A) expense was 23.9 percent of net revenues in the fourth quarter. On a GAAP basis, SG&A was 27.1 percent of net revenues.

Adjusted research and development (R&D) expense was 15.9 percent of net revenues in the quarter, reflecting funding actions in support of our mid- and late-stage pipeline. On a GAAP basis, R&D was 16.8 percent of net revenues.

Adjusted operating margin in the fourth quarter was 40.1 percent, compared to 35.8 percent in fourth-quarter 2014. On a GAAP basis, the operating margin was 33.0 percent.

Net interest expense was $199 million. The adjusted tax rate in the quarter was 21.6 percent and 21.1 percent on a GAAP basis.

Adjusted diluted earnings per share, excluding intangible asset amortization expense and other specified items, were $1.13 in the fourth quarter, up 27 percent. Diluted earnings per share were $0.92 on a GAAP basis.

Key Events from the Fourth Quarter

AbbVie submitted a supplemental New Drug Application (sNDA) for ibrutinib (IMBRUVICA) to the U.S. Food and Drug Administration (FDA) for use in treatment-naïve chronic lymphocytic leukemia (CLL) patients, based on results from the Phase 3 RESONATE-2 study. These data, published in The New England Journal of Medicine (NEJM), found that IMBRUVICA significantly decreased the risk of progression or death (progression-free survival, PFS) and significantly decreased the risk of death (overall survival, OS) versus chlorambucil in treatment-naïve patients 65 years and older with CLL.

AbbVie submitted a New Drug Application (NDA) and a Marketing Authorization Application (MAA) for venetoclax in patients with relapsed/refractory (R/R) CLL in patients with chromosome 17p deletion to the FDA and European Medicines Agency (EMA), respectively. Priority review status was granted by the FDA and validation provided by the EMA for these submissions based on results from a Phase 2, open-label trial that found treatment with venetoclax demonstrated a 79.4 percent overall response rate (ORR) as monotherapy treatment, including patients that achieved complete remission.

AbbVie has now received three FDA Breakthrough Therapy Designations for venetoclax. The first designation was received early last year for the treatment of patients with R/R CLL with chromosome 17p deletion. The second designation for venetoclax was received earlier this month for combination therapy with rituximab for patients with R/R CLL, including those with chromosome 17p deletion. A third designation was received this week for venetoclax in combination with hypomethylating agents (HMAs) in patients with untreated (treatment-naïve) acute myeloid leukemia (AML) who are ineligible to receive standard induction therapy (high-dose chemotherapy).

AbbVie submitted a sNDA to the FDA for labeling considerations based on safety and efficacy results from the Phase 3 HELIOS trial of IMBRUVICA in patients with R/R CLL. The trial found that treatment with IMBRUVICA plus bendamustine and rituximab, versus placebo plus rituximab, significantly reduced the risk of disease progression or death by 80 percent and significantly improved ORR compared to placebo plus rituximab in previously-treated CLL/SLL patients.

The FDA accepted AbbVie’s sNDA and granted priority review for VIEKIRA PAK without ribavirin in patients with genotype 1b (GT1b) chronic hepatitis C virus infection (HCV) and compensated cirrhosis (Child-Pugh A). The application was supported by data from the TURQUOISE-III study, which showed 100 percent sustained virologic response at 12 weeks post-treatment (SVR12) in this patient population.

AbbVie announced that the FDA accepted its NDA for a once-daily, fixed-dosed formulation of VIEKIRA PAK to treat GT1 HCV. The proposed dosing for the fixed-dose formulation is three oral tablets, taken once daily with a meal, with or without ribavirin. AbbVie anticipates regulatory action on the new formulation in 2016.

At the American Society of Hematology (ASH) (Free ASH Whitepaper)’s Annual Meeting (ASH) (Free ASH Whitepaper) in December 2015, AbbVie presented new results from a Phase 2, open-label study of venetoclax in treatment-naïve patients 65 years and older with AML who were not eligible for intensive-induction chemotherapy. These data found that combination treatment with venetoclax and hypomethylating agents resulted in complete response rates of approximately 71 percent, which is roughly double the response rate that would be expected with current standard of care treatment. AbbVie plans to initiate registration studies of venetoclax for this indication in 2016.

AbbVie’s IMBRUVICA partner Janssen presented results from the Phase 3 RAY study which demonstrated treatment with IMBRUVICA significantly prolonged PFS and improved ORR in patients with R/R mantle-cell lymphoma (MCL), compared with temsirolimus. Specifically, IMBRUVICA was found to reduce the risk of disease progression or death by 57 percent with a median follow-up of 20 months. These data were also published online in The Lancet.

AbbVie announced that data from a Phase 2 study evaluating IMBRUVICA therapy in treatment-naïve patients with follicular lymphoma (FL) demonstrated that a combination of IMBRUVICA and rituximab was well-tolerated and associated with ORR of 82 percent.

AbbVie presented data from its next-generation HCV regimen (ABT-493 and ABT-530) being evaluated as a pan-genotypic, once-daily treatment option for patients with HCV at the 2015 Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). Results demonstrated 12 weeks of treatment resulted in 97-100 percent SVR12 in GT1 non-cirrhotic HCV, 96-100 percent in genotype (GT2) and 83-94 percent in genotype 3 (GT3) patients. Additionally, data from the SURVEYOR-I study were also presented at the meeting and showed that non-cirrhotic GT1 HCV patients who received shorter duration of treatment for 8 weeks with ABT-493 and ABT-530 achieved SVR12 rates of 97 percent. The company initiated Phase 3 studies in the fourth quarter of 2015.

At the American College of Rheumatology (ACR) Annual Meeting, AbbVie presented the full 12-week, Phase 2b safety data for ABT-494, an investigational oral JAK-1 inhibitor, from the BALANCE-I study (efficacy data was previously top-lined). This study evaluated a broad dose range to understand the boundaries of JAK-1 selectivity and the efficacy of ABT-494 versus placebo in previously treated patients with rheumatoid arthritis (RA) with persistent and active disease. The study met its primary endpoint, achieving an ACR20 response after 12 weeks of treatment using an LOCF approach, and ACR20 for all dose levels. The BALANCE I and II results support the company’s decision to move ABT-494 into Phase 3 studies with a once-daily dose. The Phase 3 program was initiated in late 2015 and a Phase 2 trial of ABT-494 is ongoing for the treatment of Crohn’s disease.

The FDA approved Empliciti (elotuzumab) for the treatment of multiple myeloma (MM) as a combination therapy in patients who have received one to three prior therapies. Empliciti was co-developed by AbbVie and Bristol-Myers Squibb (BMS) and will be marketed by BMS. This approval was based on data from a Phase 3 study which demonstrated that patients treated with Empliciti plus standard of care therapy achieved a 30 percent reduction in the risk of disease progression or death compared to standard of care alone. This is the first FDA approval for an immune-stimulatory antibody for MM in this indication.

Confirming Full-Year 2016 Outlook

AbbVie is confirming its diluted earnings-per-share guidance of $4.90 to $5.10 on an adjusted basis for the full-year 2016, representing strong double-digit growth versus 2015 and positioning AbbVie to be among the industry leaders for growth again in 2016. The company’s 2016 adjusted diluted earnings-per-share guidance excludes $0.45 per share of intangible asset amortization expense and other specified items. Including these items, AbbVie’s diluted earnings-per-share guidance is $4.45 to $4.65 on a GAAP basis.

COMMISSION IMPLEMENTING DECISION of 29.1.2016 concerning the transfer of the designation of “Chimeric monoclonal antibody to O-acetyl-GD2 antigen” as an orphan medicinal product under Regulation (EC) No 141/2000 of the European Parliament and of the Council

EN EN EUROPEAN COMMISSION Bruxelles, 29.1.2016 C(2016)679 (final) COMMISSION IMPLEMENTING DECISION of 29.1.2016 concerning the transfer of the designation of "Chimeric monoclonal antibody to O-acetyl-GD2 antigen" as an orphan medicinal product under Regulation (EC) No 141/2000 of the European Parliament and of the Council (Text with EEA relevance) (ONLY THE FRENCH TEXT IS AUTHENTIC)

EN 1 EN COMMISSION IMPLEMENTING DECISION of 29.1.2016 concerning the transfer of the designation of "Chimeric monoclonal antibody to O-acetyl-GD2 antigen" as an orphan medicinal product under Regulation (EC) No 141/2000 of the European Parliament and of the Council (Text with EEA relevance) (ONLY THE FRENCH TEXT IS AUTHENTIC) THE EUROPEAN COMMISSION, Having regard to the Treaty on the Functioning of the European Union, Having regard to Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products 1, and in particular the first sentence of Article 5(8) thereof, Having regard to the application submitted on 11 January 2016 by Atlab Pharma SAS under Article 5(11) of Regulation (EC) No 141/2000, Having regard to the opinion of the European Medicines Agency, formulated on 12 January 2016 on the transfer of a marketing authorisation, Whereas: (1) By Decision C(2015)180(final) of 15 January 2015 the medicinal product "Chimeric monoclonal antibody to O-acetyl-GD2 antigen" was designated as an orphan medicinal product and entered in the Community Register of Orphan Medicinal Products pursuant to Article 5(9) of Regulation (EC) No 141/2000. (2) A change of designation holder is a change of an administrative nature, which does not affect the scientific characteristics of the medicinal product already designated as an orphan medicinal product. (3) The application should therefore be granted, HAS ADOPTED THIS DECISION: Article 1 The designation of the medicinal product "Chimeric monoclonal antibody to O-acetyl-GD2 antigen" as an orphan medicinal product, entered in the Community Register of Orphan Medicinal Products under number EU/3/14/1416 and held by Atlab Pharma SAS, is transferred to OGD2 Pharma. 1 OJ L 18, 22.1.2000, p.1. EN 2 EN Article 2 This Decision is addressed to: 1. OGD2 Pharma, 3 chemin du Pressoir Chênaie, 44100 Nantes, France and 2. Atlab Pharma SAS, 3 chemin du Pressoir Chênaie, 44100 Nantes, France. Done at Brussels, 29.1.2016 For the Commission Xavier PRATS MONNÉ Director-General

Oxford BioMedica Announces Initiation of Second CART Programme for Major Pharmaceutical Company

On January 29, 2016 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE: OXB), a leading gene and cell therapy group, reported that the Group has initiated work on a second Chimeric Antigen Receptor T cell (CART) programme for an undisclosed indication (Press release, Oxford BioMedica, JAN 29, 2016, View Source [SID:1234508910]). Under an agreement signed with Novartis in October 2014, Oxford BioMedica will undertake process development and manufacturing for the lentiviral vector associated with the new programme.

Oxford BioMedica is currently manufacturing lentiviral vector expressing CTL019 for Novartis and carrying out process development work to establish the next-generation manufacturing process. The Group also granted Novartis a non-exclusive licence in oncology under the Group’s LentiVector platform and an exclusive licence for the worldwide development and commercialisation of all CART cell products arising from the process development collaboration. In return, Oxford BioMedica will receive undisclosed royalties on potential future sales of CART products covered by the agreement.

Commenting on the announcement, John Dawson, Chief Executive Officer of Oxford BioMedica, said: "We are excited to be providing Novartis with the licence, process development and manufacturing that they require for CTL019 and now for a second CART programme. Oxford BioMedica is recognised as a world leader in the field of lentiviral vectors and we are delighted to be supporting clinical programmes where the need for this type of medical intervention is vital."

Bristol-Myers Squibb and AbbVie Receive Positive CHMP Opinion for Investigational Antibody, Empliciti (elotuzumab), for the Treatment of Multiple Myeloma in Patients Who Have Received at Least One Prior Therapy

On January 29, 2016 Bristol-Myers Squibb Company (NYSE:BMY) and AbbVie (NYSE:ABBV) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending that Empliciti (elotuzumab), an investigational immunostimulatory antibody, be granted approval for the treatment of multiple myeloma as combination therapy with Revlimid (lenalidomide) and dexamethasone in patients who have received at least one prior therapy (Press release, Bristol-Myers Squibb, JAN 29, 2016, View Source [SID:1234508909]). The application now will be reviewed by the European Commission, which has the authority to approve medicines for the European Union (EU).

"Today’s positive CHMP recommendation means we are one step closer to offering a new type of treatment for patients in Europe with multiple myeloma who have received at least one prior therapy," said Michael Giordano, M.D., senior vice president, head of Development, Oncology, Bristol-Myers Squibb. "We look forward to the European Commission’s decision and the opportunity to extend our leading Immuno-Oncology science to patients with multiple myeloma."

The CHMP positive opinion is based on data from the Phase 3, open-label ELOQUENT-2 study, which evaluated Empliciti in combination with lenalidomide and dexamethasone (ERd) versus lenalidomide and dexamethasone (Rd) alone. The results of this trial showed a 30% reduction in the risk of disease progression or death with ERd compared to Rd alone and, at the two year time point, ERd delivered a 52% relative improvement in progression-free survival. The most common adverse reactions in ERd and Rd, respectively (>20%) were fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%) and pneumonia (20.1%, 14.2%). These results were published in The New England Journal of Medicine on June 2, 2015.

About Empliciti

Empliciti is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.

Empliciti has a dual mechanism-of-action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.

On November 30, 2015, the U.S. Food and Drug Administration approved Empliciti in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received one to three prior therapies. The safety and efficacy of Empliciti is still being evaluated by other health authorities.

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

About Multiple Myeloma

Multiple myeloma is a hematologic, or blood, cancer that develops in the bone marrow. It occurs when a plasma cell, a type of cell in the soft center of bone marrow, becomes cancerous and multiplies uncontrollably. Common symptoms of multiple myeloma include bone pain, fatigue, kidney impairment and infections.

Despite advances in multiple myeloma treatment over the last decade, less than half of patients survive for five or more years after diagnosis. A common characteristic for many patients is that they experience a cycle of remission and relapse, in which they stop treatment for a short time, but eventually return to a treatment shortly after. It is estimated that annually, more than 114,200 new cases of multiple myeloma are diagnosed and more than 80,000 people die from the disease globally.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

EMPLICITI can cause infusion reactions. Common symptoms include fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
Premedicate with dexamethasone, H1 Blocker, H2 Blocker, and acetaminophen prior to infusing with EMPLICITI.
Infections

In a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd) and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4 infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were 9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor patients for development of infections and treat promptly.
Second Primary Malignancies

In a clinical trial of patients with multiple myeloma (N=635), invasive second primary malignancies (SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic malignancies were the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). Monitor patients for the development of SPMs.
Hepatotoxicity

Elevations in liver enzymes (AST/ALT greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and 0.6% (Rd). Two patients experiencing hepatotoxicity discontinued treatment; however, 6 out of 8 patients had resolution and continued treatment. Monitor liver enzymes periodically. Stop EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.
Interference with Determination of Complete Response

EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
Pregnancy/Females and Males of Reproductive Potential

There are no studies with EMPLICITI with pregnant women to inform any drug associated risks.
There is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide and it is contraindicated for use in pregnancy. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.
Adverse Reactions

Infusion reactions were reported in approximately 10% of patients treated with EMPLICITI with lenalidomide and dexamethasone. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients.
Serious adverse reactions were 65.4% (ERd) and 56.5% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%), pyrexia (6.9%, 4.7%), respiratory tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%).
The most common adverse reactions in ERd and Rd, respectively (>20%) were fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and pneumonia (20.1%, 14.2%).

AbbVie Initiates Enrollment in Phase 3 Clinical Program for Elagolix in Patients with Uterine Fibroids

On January 28, 2016 AbbVie (NYSE: ABBV), in cooperation with Neurocrine Biosciences, Inc. (NASDAQ: NBIX), reported the initiation of the first of two planned Phase 3 clinical studies evaluating the safety and efficacy of Elagolix alone or in combination with add-back therapy compared to placebo (Press release, Neurocrine Biosciences, JAN 28, 2016, View Source;p=RssLanding&cat=news&id=2137247 [SID:1234509041]). 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. AbbVie is eager to further explore Elagolix’s potential to address this unmet need," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie.

The Elagolix Phase 3 uterine fibroid clinical development program is part of AbbVie’s pipeline and includes two replicate, randomized, parallel, double-blind, placebo-controlled clinical trials. Each trial is expected to enroll approximately 400 subjects for an initial six-month placebo-controlled dosing period, after which, subjects who are eligible will have an option to continue for an additional six-month dosing period in a safety and efficacy extension study. AbbVie will make a $15MM milestone payment to Neurocrine Biosciences upon enrollment of the first patient.

Uterine fibroids (also called leiomyomas or myomas) are noncancerous muscle tissue tumors of the uterus.1 Fibroids are most common in women aged 30-40 years but can occur at any age.1 They can range in size from nearly undetectable to bulky masses that can distort the uterus.2 Fibroids can be asymptomatic but in some women cause symptoms such as: longer, more frequent, or heavy menstrual bleeding; menstrual pain; vaginal bleeding at time other than menstruation; pain in the abdomen or lower back; pain during sex; difficulty urinating; frequent urination; constipation or rectal pain.1

About Elagolix
Elagolix is an orally administered gonadotropin-releasing hormone (GnRH) antagonist that is currently being investigated in diseases that are mediated by sex hormones, such as uterine fibroids and endometriosis. To date, Elagolix has been studied in over 40 clinical trials totaling more than 3,000 subjects. Phase 3 trials of Elagolix for the management of endometriosis-associated pain are also ongoing.