On July 27, 2018 Novartis reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of Tafinlar (dabrafenib) in combination with Mekinist (trametinib) for the adjuvant treatment of adult patients with stage III melanoma with a BRAF V600 mutation, following complete resection (Press release, Novartis, JUL 27, 2018, View Source [SID1234527943]). The CHMP recommendation is based on findings from the COMBI-AD study, which was published in The New England Journal of Medicine (NEJM).

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Patients who have been diagnosed with stage III melanoma are at a higher risk of recurrence after surgical resection. The COMBI-AD study found a statistically significant 53% reduction in the risk of recurrence or death in patients treated with the BRAF and MEK inhibitor combination therapy after surgical resection versus placebo[1].

With an estimated 6,000 stage III BRAF mutant melanoma skin cancers diagnosed across Europe each year[2], this potential approval may provide patients in the EU the opportunity for a targeted combination therapy that doubles relapsed-free survival versus a placebo.

"Melanoma is an aggressive, highly recurrent and often fatal disease. In advanced melanoma, we’ve demonstrated the ability to reduce the risk of death or recurrence by more than half," said Liz Barrett, CEO, Novartis Oncology. "Today’s CHMP opinion brings us another step closer to reimagining earlier stage therapy for patients throughout Europe and making strides to bring improved outcomes for people living with melanoma."

"These relapse-free survival results are unprecedented," said lead investigator Axel Hauschild, MD, PhD, Professor of Dermatology, University Hospital Schleswig-Holstein, in Kiel, Germany. "The overall survival improvements also demonstrated by Tafinlar in combination with Mekinist, among other key secondary endpoints, are encouraging in the treatment of stage III BRAF V600E/K mutation-positive melanoma. Adjuvant treatment options are critical for this patient community at risk for recurrence."

About COMBI-AD Study
The COMBI-AD study evaluated Tafinlar + Mekinist among patients with stage III, BRAF V600E/K-mutant melanoma without prior anticancer therapy, randomized within 12 weeks of complete surgical resection. Patients received the Tafinlar (150 mg BID) and Mekinist (2 mg QD) combination (n = 438) or matching placebos (n = 432). After a median follow-up of 2.8 years, the primary endpoint was met in that combination therapy significantly reduced the risk of disease recurrence or death by 53% vs. placebo (HR: 0.47 [95% CI: 0.39-0.58]; median not yet reached vs. 16.6 months, respectively; p<0.001). The relapse-free survival benefit among the combination arm was observed across all patient subgroups, including stage III A, B and C. The estimated one-year, two-year, and three-year RFS were consistently higher than placebo (one year: 88% vs. 56%; two year: 67% vs. 44%; three year: 58% vs. 39%). The combination treatment group also saw an improvement in a key secondary endpoint of OS (HR: 0.57 [95% CI: 0.42-0.79] p=0.0006, which did not cross the predefined interim analysis boundary of p=0.000019 to claim statistical significance). Other secondary endpoints where the combination demonstrated a clinically meaningful benefit include distant metastasis-free survival (DMFS) (HR: 0.51 [95% CI: 0.40-0.65]), and freedom from relapse (FFR) (HR: 0.47 [95% CI: 0.39-0.57])[1].

Adverse events (AEs) were consistent with other Tafinlar + Mekinist studies, and no new safety signals were reported. Of patients treated with the combination, the most frequently reported AE’s were pyrexia, fatigue, nausea, headache, chills, diarrhea, vomiting, arthralgia and rash[1].

About Melanoma
There are nearly 200,000 new diagnoses of melanoma (stages 0-IV) worldwide each year, approximately half of which have BRAF mutations. Biomarker tests can determine whether a tumor has a BRAF mutation[3],[4].

Melanoma is staged by how far it has metastasized. In stage III melanoma, tumors have spread to the regional lymph nodes, presenting a higher risk of recurrence or metastases[4]4. Patients who receive surgical treatment for stage III melanoma may have a high risk of recurrence because melanoma cells can remain in the body after surgery; almost half (44%) of patients receiving placebo per the COMBI-AD study had a recurrence of disease within the first year[1],[5]. Adjuvant therapy is additional treatment given after surgical resection, and may be recommended for patients with high-risk melanoma to help reduce the risk of melanoma returning[5].

About Tafinlar + Mekinist Combination
In the EU, Tafinlar in combination with Mekinist is approved for the treatment of patients with a BRAF V600 mutation in metastatic melanoma and advanced non-small cell lung cancer.

In the US, Tafinlar in combination with Mekinist is approved for the treatment of patients with a BRAF V600 E or K mutation, detected by an FDA-approved test, in unresectable or metastatic melanoma, adjuvant treatment of melanoma, non-small cell lung cancer (V600 E only) and anaplastic thyroid cancer.

Tafinlar and Mekinist are also indicated in more than 60 countries worldwide, including the US and EU, as single agents to treat patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of Tafinlar and Mekinist have not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that Tafinlar and Mekinist will become commercially available for additional indications anywhere else in the world.

Tafinlar + Mekinist Combination Important Safety Information
Tafinlar + Mekinist combination may cause serious side effects.

Tafinlar in combination with Mekinist should only be used to treat patients with a change (mutation) in the BRAF gene; therefore, doctors should test their patients before treatment, as patients without a BRAF mutation and with a RAS mutation can be at risk of increased cell proliferation in the presence of a BRAF inhibitor.

Doctors should also consider other treatment options for their patients if they had been previously treated with a BRAF inhibitor as single agent, as the limited data available have shown that the efficacy of Tafinlar + Mekinist is lower in these patients.

When Tafinlar is used in combination with Mekinist, or when Tafinlar is administered as monotherapy, it can cause new cancers (both skin cancer and non-skin cancer). Patients should be advised to contact their doctor immediately for any new lesions, changes to existing lesions on their skin, or signs and symptoms of other malignancies.

Tafinlar in combination with Mekinist, or Mekinist alone, can cause severe bleeding, and in some cases can lead to death. Patients should be advised to call their healthcare provider and get medical help right away if they have headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like "coffee grounds," have red or black stools that look like tar, or any unusual signs of bleeding.

Tafinlar in combination with Mekinist, or either drug alone, can cause severe eye problems that can lead to blindness. Patients should be advised to call their healthcare provider right away if they get these symptoms of eye problems: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

Tafinlar in combination with Mekinist, or Tafinlar alone, can cause fever which may be serious. When taking Tafinlar in combination with Mekinist, fever may happen more often or may be more severe. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their healthcare provider right away if they get a fever above 38.5oC (101.3oF) while taking Tafinlar.

Tafinlar in combination with Mekinist, or Mekinist alone, can affect how well the heart pumps blood. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their healthcare provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

Tafinlar in combination with Mekinist, or Tafinlar alone, can cause abnormal kidney function or inflammation of the kidney. Abnormal kidney function may happen more often for patients with fever or too much fluid loss. Patients should be advised to call their healthcare provider right away if they have a fever above 38.5oC (101.3oF), decreased urine, fatigue, loss of appetite or discomfort in lower abdomen or back. Tafinlar has not been studied in patients with renal insufficiency (defined as creatinine > 1.5 x ULN) therefore caution should be used in this setting.

Tafinlar in combination with Mekinist, or Mekinist alone, can cause abnormal liver function. A patient may feel tired, lose appetite, yellow skin, dark urine colour, or discomfort in abdomen. The liver function abnormality needs to be assessed by laboratory test of the blood. Patients should consult their healthcare provider if they have such experience. Administration of Tafinlar or Mekinist should be done with caution in patients with moderate to severe hepatic impairment.

Elevations in blood pressure have been reported in association with Mekinist in combination with Tafinlar, or with Mekinist alone, in patients with or without pre-existing hypertension. Patients should be advised to monitor blood pressure during treatment with Mekinist and control potential hypertension by standard therapy, as appropriate.

Tafinlar in combination with Mekinist, or Mekinist alone, can cause inflammation of the lung tissue. Patients should notify their doctor if they experience any new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Rash is a common side effect of Tafinlar in combination with Mekinist, or with Mekinist alone. Tafinlar in combination with Mekinist, or Mekinist alone, can also cause other skin reactions which can be severe, and may need to be treated in a hospital. Patients should be advised to call their healthcare provider if they get any of the following symptoms: skin rash that bothers them or does not go away, acne, redness, swelling, peeling, or tenderness of hands or feet, skin redness.

Tafinlar in combination with Mekinist, or Mekinist alone, can cause muscle breakdown, a condition called Rhabdomyolysis. Patients experiencing muscle pain, tenderness, weakness or a swelling of their muscles should contact their healthcare provide immediately.

Tafinlar in combination with Mekinist, or Tafinlar alone, can uncommonly cause an inflammation of the pancreas (pancreatitis). Patients should be promptly investigated if they experience unexplained abdominal pain and closely monitored if they re-start Tafinlar after a prior episode of pancreatitis.

Tafinlar in combination with Mekinist, or Mekinist alone, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

Mekinist in combination with Tafinlar, or Mekinist alone, may increase the risk of developing holes in the stomach or intestine (gastrointestinal perforation). Treatment with Mekinist alone or in combination with Tafinlar should be used with caution in patients with risk factors for gastrointestinal perforation, including concomitant use of medications with a recognized risk of gastrointestinal perforation.

Tafinlar and Mekinist both can cause harm to an unborn baby when taken by a pregnant woman. Tafinlar can also render hormonal contraceptives ineffective.

The most common side effects of Tafinlar + Mekinist combination include fever, nausea, diarrhea, fatigue, chills, headache, vomiting, joint pain, high blood pressure, rash and cough. The incidence and severity of fever is increased when Mekinist is used in combination with Tafinlar.

Patients should tell their doctor of any side effect that bothers them or does not go away. These are not all of the possible side effects of Tafinlar + Mekinist combination. For more information, patients should ask their doctor or pharmacist.

Patients should take Tafinlar + Mekinist combination exactly as their health care provider tells them. Patients should not change their dose or stop taking Tafinlar + Mekinist combination unless their health care provider advises them to. Mekinist should be taken only once daily (either in the morning or evening, at the same time as Tafinlar). The first and second doses of Tafinlar should be taken approximately 12 hours apart. Patients should take Tafinlar + Mekinist at least 1 hour before or 2 hours after a meal. Do not take a missed dose of Tafinlar within 6 hours of the next dose of Tafinlar. Do not open, crush, or break Tafinlar capsules. Do not take a missed dose of Mekinist within 12 hours of the next dose of Mekinist.

Please see full Prescribing Information for Tafinlar and Mekinist.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "positive CHMP opinion," "expected," "recommending," "recommendation," "potential," "may," "reimagining," "encouraging," "will," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Tafinlar and Mekinist, or regarding potential future revenues from Tafinlar and Mekinist and such other products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Tafinlar and Mekinist will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that Tafinlar and Mekinist will be commercially successful in the future. In particular, our expectations regarding Tafinlar and Mekinist could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payer and general public pricing and reimbursement pressures; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

On July 26, 2018 Alkermes plc (Nasdaq: ALKS) reported financial results for the second quarter of 2018 (Press release, Alkermes, JUL 26, 2018, View Source;p=RssLanding&cat=news&id=2360206 [SID1234527877]).

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"Our strong second quarter results were driven by the solid growth of our proprietary commercial products, the continued strength of our royalty and manufacturing business, as well as the receipt of a $50 million payment related to our collaboration with Biogen for BIIB098," commented James Frates, Chief Financial Officer of Alkermes. "The business is performing as planned and today we are reiterating our financial expectations for 2018. As we head into a catalyst-rich second half of the year, we are well-positioned financially to drive value, grow our portfolio of commercial products and advance our late-stage pipeline."

Quarter Ended June 30, 2018 Financial Highlights

Total revenues for the quarter were $304.6 million. This compared to $218.8 million for the same period in the prior year, representing an increase of 39%. Proprietary product net sales for VIVITROL and ARISTADA were $109.8 million for the quarter, reflecting a 24% increase compared to the same period in the prior year.
Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $32.6 million for the quarter, or a basic and diluted GAAP net loss per share of $0.21. This compared to GAAP net loss of $43.0 million, or a basic and diluted GAAP net loss per share of $0.28, for the same period in the prior year.
Non-GAAP net income was $45.6 million for the quarter, or non-GAAP basic and diluted earnings per share of $0.29. This compared to non-GAAP net income of $1.2 million, or non-GAAP basic and diluted earnings per share of $0.01, for the same period in the prior year.
"VIVITROL and ARISTADA continue to demonstrate solid growth and perform in-line with our expectations. Our proprietary commercial portfolio is a key growth driver for Alkermes, and we are confident about the prospects ahead for these important products," stated Jim Robinson, President and Chief Operating Officer of Alkermes. "In particular, the launch of ARISTADA INITIO is an important opportunity to support continuity of care and address a critical unmet need for patients, as ARISTADA is now the first and only long-acting atypical antipsychotic that can be fully dosed on day one for up to two months. ARISTADA INITIO represents a key addition to the treatment paradigm for schizophrenia and provides a platform to further expand utilization of ARISTADA."

Quarter Ended June 30, 2018 Financial Results

Revenues

Net sales of VIVITROL were $76.2 million, compared to $66.1 million for the same period in the prior year, representing an increase of approximately 15%.
Net sales of ARISTADA were $33.6 million, compared to $22.7 million for the same period in the prior year, representing an increase of approximately 48%.
Manufacturing and royalty revenues from RISPERDAL CONSTA, INVEGA SUSTENNA/XEPLION and INVEGA TRINZA/TREVICTA were $85.2 million, compared to $82.2 million for the same period in the prior year.
Manufacturing and royalty revenues from AMPYRA/FAMPYRA1 were $19.7 million, compared to $25.3 million for the same period in the prior year.
License revenues from the collaboration with Biogen for BIIB098 (formerly ALKS 8700) were $48.3 million.
Research and development revenues were $18.3 million, of which $17.2 million related to the collaboration with Biogen for BIIB098.
Costs and Expenses

Operating expenses were $304.7 million, compared to $263.4 million for the same period in the prior year, primarily reflecting increased investment in the commercialization of VIVITROL and ARISTADA.
Other expense during the quarter included a $19.6 million charge due to a decrease in the fair value of contingent consideration, related to Recro Pharma, Inc.’s receipt of a complete response letter from the United States (U.S.) Food and Drug Administration (FDA) regarding the New Drug Application (NDA) for IV Meloxicam.
"With a growing proprietary commercial portfolio and partnered royalty and manufacturing business approaching $1 billion in revenue in 2018, Alkermes is in a strong position to create significant long-term value. As we head into the second half of 2018, we are on the threshold of important value inflections across our development portfolio," said Richard Pops, Chief Executive Officer of Alkermes. "For ALKS 5461 for major depressive disorder, the regulatory review is underway and we are preparing for an Advisory Committee meeting in the fourth quarter. For ALKS 3831 for schizophrenia, enrollment of the ENLIGHTEN-2 pivotal study is complete and we expect topline data in the fourth quarter of 2018. In addition, we are on track to submit the NDA for BIIB098 toward year-end, and we look forward to presenting initial data from the ALKS 4230 phase 1 study and expanding into combination therapy later this year."

Recent Events:

ARISTADA INITIO: Following recent FDA approval, ARISTADA INITIO is now commercially available. The ARISTADA INITIO regimen2 provides physicians with an opportunity to initiate patients onto any dose of ARISTADA on day one.
ALKS 5461: Data on the long-term safety, tolerability and durability of antidepressant effect of ALKS 5461 were presented at the American Psychiatric Association (APA) and American Society of Clinical Psychopharmacology (ASCP) annual meetings.
ALKS 3831: The company presented data from the ALKS 3831 preclinical program and phase 1 translational medicine study evaluating the metabolic profile of ALKS 3831 compared to olanzapine.
BIIB098: Alkermes received a $50 million payment from Biogen in June 2018. This payment follows Biogen’s review of preliminary gastrointestinal tolerability data from the ongoing clinical development program for BIIB098.
Financial Expectations for 2018
Alkermes reiterates its financial expectations for 2018 set forth in its press release dated April 26, 2018.

Conference Call
Alkermes will host a conference call and webcast presentation with accompanying slides at 8:30 a.m. ET (1:30 p.m. BST) on Thursday, July 26, 2018, to discuss these financial results and provide an update on the company. The webcast may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. The conference call may be accessed by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422 for international callers. The conference call ID number is 6037988. In addition, a replay of the conference call will be available from 11:00 a.m. ET (4:00 p.m. BST) on Thursday, July 26, 2018, through 5:00 p.m. ET (10:00 p.m. BST) on Thursday, Aug. 2, 2018, and may be accessed by visiting Alkermes’ website or by dialing +1 888 843 7419 for U.S. callers and +1 630 652 3042 for international callers. The replay access code is 6037988.

On July 26, 2018 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ: CTIC) reported that management plans to report its second quarter 2018 financial results on Thursday, August 2, 2018, after the close of the U.S. financial markets (Press release, CTI BioPharma, JUL 26, 2018, View Source;p=RssLanding&cat=news&id=2360352 [SID1234527899]). Following the announcement, members of the management team will host a webcast conference call to discuss the results and provide a general corporate update at 4:30 p.m. ET (1:30 p.m. PT). Access to the event can be obtained as follows:

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Thursday, August 2, 2018
1:30 p.m. PT/4:30 p.m. ET/10:30 p.m. CET
877-260-1479 (domestic)
+1 334 323 0522 (international)

To access the live audio webcast or the subsequent archived recording, visit CTI BioPharma’s website, www.ctibiopharma.com. Webcast and telephone replays of the conference call will be available at approximately two hours after completion of the call. Callers can access the replay by dialing 1-888-203-1112 (domestic) or +1 719-457-0820 (international). The access code for the replay is 3255708. The telephone replay will be available until Thursday, August 9, 2018.

On July 26, 2018 Allergan plc (NYSE: AGN) reported its second quarter 2018 performance (Press release, Allergan, JUL 26, 2018, View Source [SID1234527878]). Total second quarter 2018 GAAP net revenues were $4.12 billion, a 2.9 percent increase from the prior year quarter.

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Executive Commentary
"Allergan’s performance in the first half of 2018 demonstrates the strength of our strategy and a sharp focus on execution. We have driven strong growth in our key products and core business, delivered seven successful pivotal clinical trials for our key R&D programs and executed on our capital deployment strategy," said Brent Saunders, Chairman and CEO of Allergan.

"In the second quarter, our core business grew by 10.6 percent, led by Medical Aesthetics, BOTOX Therapeutic, VRAYLAR and LINZESS. Overall non-GAAP revenues rose 2.3 percent, even amid ongoing exclusivity challenges for older products," said Saunders. "At the same time, the positive clinical trial results on programs for migraine, glaucoma and age-related macular degeneration highlight the promise of our business for years to come."

"I’m extremely proud of the global Allergan team for their excellent work in delivering results for our customers and patients. Allergan’s many successes in the first half of 2018 demonstrate our commitment to driving long term value for shareholders."

Second Quarter 2018 Performance
GAAP operating loss in the second quarter 2018 was $467.0 million, including the impact of amortization and impairments. Non-GAAP operating income in the second quarter of 2018 was $1.97 billion, an increase of 4.6 percent versus the prior year quarter, driven by higher revenues and lower operating expenses.

Operating Expenses
Total GAAP Selling, General and Administrative (SG&A) Expense was $1.19 billion for the second quarter 2018, a decrease of 14.9 percent from the prior year quarter. Total non-GAAP SG&A expense decreased to $1.13 billion for the second quarter 2018, compared to $1.22 billion in the prior year period, driven in large part by a reduction in losses due to foreign exchange, as well as lower advertising and promotional expenses. GAAP R&D investment for the second quarter of 2018 was $689.2 million, compared to $489.4 million in the second quarter of 2017. Non-GAAP R&D investment for the second quarter 2018 was $388.9 million, compared to $393.9 million in the prior year quarter.

Asset Sales & Impairments, Net and In-Process R&D Impairments
Allergan incurred in-process research and development impairments in the three months ended June 30, 2018 of $276.0 million primarily due to a decrease in market opportunity based on clinical data relating to an eye care product acquired as part of the Allergan acquisition and timing delays in other non-strategic projects. Asset sales and impairments, net in the three months ended June 30, 2018 of $259.6 million were primarily related to an impairment on a non-strategic dermatology product held for sale based on estimates of current market value. The Company excludes asset sales and impairments, net and in-process research and development impairments from its non-GAAP performance net income attributable to shareholders as well as from Adjusted EBITDA and non-GAAP Operating Income.

Amortization, Other Income (Expense) Net, Tax and Capitalization
Amortization expense for the second quarter 2018 was $1.70 billion, compared to $1.76 billion in the second quarter of 2017. Other income (expense), net of $215.4 million in the three months ended June 30, 2018 was primarily attributed to a gain on selling the Company’s remaining equity stake in Teva as well as a gain on the divestiture of a business previously held for sale. The Company’s GAAP tax rate was 1.1 percent in the second quarter 2018. The Company’s non-GAAP adjusted tax rate was 14.3 percent in the second quarter 2018. As of June 30, 2018, Allergan had cash and marketable securities of $1.70 billion and outstanding indebtedness of $25.35 billion.

SECOND QUARTER 2018 BUSINESS SEGMENT RESULTS

U.S. Specialized Therapeutics
U.S. Specialized Therapeutics net revenues grew 6.5 percent in the second quarter of 2018 from the prior year quarter to $1.83 billion, driven primarily by growth in Medical Aesthetics, including BOTOX Cosmetic, ALLODERM and the addition of CoolSculpting, as well as growth in BOTOX Therapeutic. Demand growth across the U.S. Specialized Therapeutics portfolio was offset in part by lower net selling prices for RESTASIS and decreased revenues in Medical Dermatology due to generic pressure. Segment gross margin for the second quarter of 2018 was 91.9 percent, also impacted by CoolSculpting. Segment contribution for the second quarter 2018 remained strong at $1.29 billion, an increase of 9.1 percent versus the prior year quarter.

Medical Aesthetics

Facial Aesthetics
BOTOX Cosmetic net revenues rose 12.5 percent in the second quarter of 2018 from the prior year quarter to $236.5 million.
JUVÉDERM Collection (defined as JUVÉDERM, VOLUMA and other fillers) net revenues in the second quarter of 2018 were $139.8 million, an increase of 10.8 percent versus the prior year quarter.
Regenerative Medicine
ALLODERM net revenues in the second quarter of 2018 grew 26.6 percent from the prior year quarter to $107.1 million.
Body Contouring
CoolSculpting net revenues (including both CoolSculpting Systems/Applicators and Consumables) in the second quarter of 2018 were $108.3 million. The CoolSculpting acquisition closed on April 28, 2017.
Neurosciences & Urology

BOTOX Therapeutic net revenues in the second quarter of 2018 were $404.7 million, an increase of 16.7 percent versus the prior year quarter.
Eye Care

RESTASIS net revenues in the second quarter of 2018 were $318.2 million, a decrease of 5.4 percent versus the prior year quarter.
ALPHAGAN/COMBIGAN net revenues in the second quarter of 2018 were $98.1 million, compared with $96.4 million in the prior year quarter.
OZURDEX net revenues in the second quarter of 2018 increased 10.8 percent from the prior year quarter to $27.6 million.
U.S. General Medicine
U.S. General Medicine net revenues in the second quarter 2018 were $1.32 billion, a decrease of 7.5 percent versus the prior year quarter, impacted by lower revenues from NAMENDA XR and ESTRACE due to generic competition, offset by strong demand growth from VRAYLAR, LINZESS, Lo LOESTRIN and anti-infectives including AVYCAZ. Segment gross margin for the second quarter of 2018 was 84.7 percent. Selling and marketing expenses in the segment were $254.8 million, a decrease of 11.6 percent versus the prior year quarter, due in part to sales force expense reductions as a result of previous restructurings. Segment contribution for the second quarter 2018 was $828.7 million.

Central Nervous System

VRAYLAR net revenues grew 72.2 percent in the second quarter of 2018 from the prior year quarter to $114.2 million.
VIIBRYD/FETZIMA net revenues in the second quarter of 2018 were $86.7 million, compared with $85.2 million in the prior year quarter.
NAMENDA XR net revenues in the second quarter of 2018 were $3.4 million, versus $118.7 million in the prior year quarter, impacted by loss of patent exclusivity for NAMENDA XR in February 2018.
Gastrointestinal, Women’s Health & Diversified Brands

LINZESS net revenues in the second quarter of 2018 were $191.8 million, an increase of 14.3 percent versus the prior year quarter.
Lo LOESTRIN net revenues in the second quarter of 2018 were $127.8 million, an increase of 13.1 percent versus the prior year quarter.
BYSTOLIC/BYVALSON net revenues in the second quarter of 2018 were $148.1 million, compared to $150.7 million in the prior year quarter.
International
International net revenues in the second quarter of 2018 were $948.9 million, an increase of 8.1 percent versus the prior year quarter excluding foreign exchange impact, driven by growth in Medical Aesthetics, Eye Care and BOTOX Therapeutic. Segment gross margin for the second quarter of 2018 was 85.3 percent. Segment contribution was $529.4 million.

Facial Aesthetics

BOTOX Cosmetic net revenues in the second quarter of 2018 were $171.4 million, an increase of 14.1 percent versus the prior year quarter excluding foreign exchange impact, driven by continued strong growth in Europe and Asia Pacific/Middle East/Africa.
JUVÉDERM Collection net revenues in the second quarter of 2018 were $156.1 million, an increase of 11.2 percent versus the prior year quarter excluding foreign exchange impact, reflecting continued strong growth in Latin America/Canada and Asia Pacific/Middle East/Africa.
Eye Care

LUMIGAN/GANFORT net revenues in the second quarter of 2018 were $100.5 million, an increase of 1.6 percent versus the prior year quarter excluding foreign exchange impact.
OZURDEX net revenues in the second quarter of 2018 were $67.9 million, up 27.5 percent versus the prior year quarter excluding foreign exchange impact, reflecting continued strong growth in all regions.
Botox Therapeutic

BOTOX Therapeutic net revenues in the second quarter of 2018 were $104.6 million, an increase of 8.1 percent versus the prior year quarter excluding foreign exchange impact, reflecting growth in Europe and Latin America/Canada.
NEW SHARE REPURCHASE PROGRAM

Allergan’s Board of Directors has authorized a new $2.0 billion share repurchase program as part of the Company’s capital allocation strategy. Allergan expects to deploy the program over the next 12 months. The Company completed the $2 billion share repurchase that was previously authorized by the board in September 2017.

Allergan reaffirmed its commitment to maintaining investment grade credit ratings and achieving a net debt to adjusted EBITDA ratio of less than 2.5X by the end of 2020.

These actions reflect the Company’s conviction in its strategy and strong future cash flow position, allowing for periodic return of cash to shareholders through dividends and share buybacks while maintaining investment grade ratings and continuing its strategy to pay down debt.

PIPELINE UPDATE

Allergan R&D continues to deliver on its pipeline. Key development highlights included:

Regulatory Milestones & Clinical Updates

Allergan announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for AGN-241751, an investigational new treatment for Major Depressive Disorder (MDD). AGN-241751 is a novel, oral NMDA modulator that recently entered Phase 2 development.
Allergan announced positive topline results in the second of two pivotal phase 3 clinical trials evaluating Ubrogepant, an orally-administered calcitonin gene-related peptide (CGRP) receptor antagonist for the acute treatment of migraine. The results from the ACHIEVE I (UBR-MD-01) and ACHIEVE II (UBR-MD-02) studies support the efficacy, safety and tolerability profile of Ubrogepant. Allergan anticipates filing of a New Drug Application (NDA) to the FDA in 2019.

Allergan announced positive results from a Phase 2b/3 clinical trial evaluating the efficacy, safety, and tolerability of Atogepant, an oral CGRP receptor antagonist in development for migraine prevention. Allergan will continue with its Phase 3 program for Atogepant following discussions with regulatory authorities.
Allergan and Molecular Partners announced two positive Phase 3 clinical trials on Abicipar for the treatment of neovascular age-related macular degeneration. The two identical studies demonstrated that both the 8-week and 12-week treatment regimens met the pre-specified primary endpoint of non-inferiority to Ranibizumab. The filing for Abicipar is planned for the first half of 2019. Allergan will be requesting a meeting with the FDA to discuss our Biologics License Application (BLA) submission.

Allergan announced positive topline Phase 3 results for Bimatoprost SR, the first-in-class sustained-release, biodegradable implant for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Additional safety data from the study and results from a second Phase 3 study with an identical design will be reported in the first half of 2019. Allergan anticipates filing of an NDA to the FDA in the second half of 2019.
Allergan expanded the REFRESH portfolio with the launch of REFRESH REPAIR Lubricant Eye Drops. The over-the-counter artificial tear formulation is clinically proven to treat the signs and symptoms of dry eye and improve visual performance due to dry eye, while offering patients improved comfort with low incidence of visual disturbances.

SECOND QUARTER 2018 CONFERENCE CALL AND WEBCAST DETAILS
Allergan will host a conference call and webcast today, Thursday, July 26, at 8:30 a.m. Eastern Time to discuss its second quarter 2018 results. The dial-in number to access the call is U.S./Canada (877) 251-7980, International (706) 643-1573, and the conference ID is 67781714. A taped replay of the conference call will also be available beginning approximately two hours after the call’s conclusion, and will remain available through 11:30 p.m. Eastern Time on August 26, 2018. The replay may be accessed by dialing (855) 859-2056 or (404) 537-3406 and entering the conference ID 67781714.
On June 1, 2018, Allergan received approval in Japan for JUVÉDERM VOLIFT XC for the treatment of nasolabial folds.

On July 26, 2018 Cytokinetics, Incorporated (Nasdaq:CYTK) reported financial results for the second quarter of 2018 (Press release, Cytokinetics, JUL 26, 2018, View Source [SID1234527900]). Net loss for the second quarter was $27.5 million, or $0.51 per share, compared to a net loss for the second quarter of 2017 of $29.1 million, or $0.60 per share. Cash, cash equivalents and investments totaled $232.0 million at June 30, 2018.

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"We made substantial progress in the second quarter of 2018 advancing programs in both our cardiac and skeletal muscle verticals," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "Following the recent presentation of positive data from our Phase 2 study of reldesemtiv in patients with SMA, we are now working with our partner, Astellas, as well as advocacy partners and clinical advisors, to consider a potential path forward in this indication, and potentially others, as we expect additional results this year. In the past quarter, we also received feedback from FDA regarding the planned second Phase 3 clinical trial of omecamtiv mecarbil in patients with heart failure, under our collaboration with Amgen; we are working toward the objective of initiating this trial before the end of the year. Finally, we continued the preclinical development of several new compounds, independently and within our collaborations, and we expect to move one or more potential drug candidates into Phase 1 clinical studies later this year."

Recent Highlights and Upcoming Milestones

Cardiac Muscle Program

omecamtiv mecarbil (cardiac myosin activator)

Continued patient enrollment in GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil. Enrollment has surpassed 50 percent completion with over 4,000 patients randomized to date having a risk profile consistent with the trial design. We expect completion of patient enrollment into GALACTIC-HF to occur during the first half of 2019.

Conducted further interactions with FDA and finalized the protocol for a second Phase 3 clinical trial of omecamtiv mecarbil. This trial is intended to evaluate the potential effect of omecamtiv mecarbil on exercise performance in patients with heart failure and will be conducted by Cytokinetics in collaboration with Amgen. We continue to work toward the objective of beginning this clinical trial by the end of the year.
Skeletal Muscle Program

reldesemtiv (next-generation FSTA)

Announced that data from the Phase 2 clinical study of reldesemtiv in patients with spinal muscular atrophy (SMA) were presented by John W. Day, M.D., Ph.D., Professor of Neurology and Pediatrics (Genetics), Stanford University, at the 2018 Annual Cure SMA Conference in Dallas. The study showed dose- and concentration-dependent increases in time to muscle fatigue as measured by changes from baseline in Six Minute Walk Distance, a sub-maximal exercise test of aerobic capacity and endurance, and Maximal Expiratory Pressure, a measure of strength of respiratory muscles, after eight weeks of treatment with reldesemtiv.

Continued site activation and patient enrollment in FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS), the Phase 2 clinical trial of reldesemtiv which is designed to assess the change from baseline in percent predicted slow vital capacity and other measures of skeletal muscle function after 12 weeks of treatment with reldesemtiv in patients with ALS. This trial has enrolled over 250 patients toward the objective of 445 patients in the trial and is being conducted by Cytokinetics in collaboration with Astellas. We expect to complete enrollment in FORTITUDE-ALS in Q4 2018 with results from this clinical trial now expected in the first half of 2019.

Completed patient enrollment in the Phase 2 clinical trial of reldesemtiv in patients with chronic obstructive pulmonary disease (COPD) which is designed to assess its effect on physical function. This trial is being conducted by Astellas in collaboration with Cytokinetics. We expect results from this clinical trial in Q3 2018.

Continued patient enrollment in the Phase 1b clinical trial of reldesemtiv in elderly subjects with limited mobility which is designed to assess its effect on measures of physical function. This trial is being conducted by Astellas in collaboration with Cytokinetics. We expect Astellas will conduct an interim analysis of data from this clinical trial in Q3 2018.
Pre-Clinical Research and Development

Continued research in collaboration with Astellas directed to the discovery of next-generation skeletal muscle activators; jointly advanced a potential drug candidate into IND-enabling studies.

Continued pre-clinical development of a next-generation cardiac muscle activator in collaboration with Amgen; we expect to submit an IND in 2018 and plan to initiate Phase 1 studies for this potential drug candidate by year-end or in early 2019.

Continued IND-enabling studies with an unpartnered cardiac sarcomere directed compound and engaged FDA in preparation for potential advancement to Phase 1 studies expected in Q4 2018.

Continued independent research activities directed to our other muscle biology research programs.
Corporate

Announced the continuation of our partnership with The ALS Association in the fight against ALS with renewal of Gold Level Sponsorship of the National Walks to Defeat ALS and Premier Level National ALS Advocacy Conference Sponsorship as well as Platinum Level Sponsorship for initiatives led by The ALS Association Golden West Chapter, including grant funding for care services for people living with ALS in the San Francisco Bay Area.

Announced an expanded partnership with Cure SMA to increase education, awareness and fundraising for SMA. As a National Platinum Partner for 2018, Cytokinetics will lend support to several of Cure SMA’s initiatives at both the local and national level to advance understanding of, and research toward potential treatments for SMA.
Financials

Revenues for the three and six months ended June 30, 2018 were $6.2 million and $11.5 million, respectively, compared to $3.1 million and $7.2 million for the corresponding periods in 2017. Revenues for the first six months of 2018 stemmed from our strategic alliance with Astellas.

Research and development expenses for the three months ended June 30, 2018 increased to $21.6 million and $43.7 million, respectively from $19.8 million and $39.1 million for the same periods in 2017, respectively, primarily due to increases in clinical trial expenses for reldesemtiv and preclinical expenses for our cardiac sarcomere directed program, offset in part by lower clinical trial and other development expenses for tirasemtiv.

General and administrative expenses for the three months ended June 30, 2018 decreased to $8.0 million from $8.4 million in 2017 primarily because of reduced precommercial and general outside services and increased to $17.3 million for the six months ended June 30, 2018 from $16.6 million for the same period in 2017, primarily due to increased general facilities-related costs.

Financial Guidance

The Company also updated financial guidance for 2018. The Company has reduced spending and revenue guidance by $5 million because of a delay in enrollment of FORTITUDE-ALS, with a corresponding reduction in cash revenues as the cost of that trial is being reimbursed by Astellas. The Company does not anticipate any change in net cash utilization. The Company estimates cash revenue will be in the range of $12 to $18 million, operating expenses will be in the range of $100 to $110 million, and net cash utilization will be approximately $100 million.

Conference Call and Webcast Information

Members of Cytokinetics’ senior management team will review the company’s second quarter results via a webcast and conference call today at 4:30 PM Eastern Time. The webcast can be accessed through the Investors & Media section of the Cytokinetics website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by dialing either (866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078 (international) and typing in the passcode 9599438.

An archived replay of the webcast will be available via Cytokinetics’ website until August 2, 2018. The replay will also be available via telephone by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (international) and typing in the passcode 9599438 from July 26, 2018 at 7:30 PM Eastern Time until August 2, 2018.