On July 19, 2019 Genmab A/S (CSE:GEN, Nasdaq:GMAB) reported that its licensing partner, Janssen Biotech, Inc., has submitted an application for the extension of the DARZALEX marketing authorization to the European Medicines Agency (EMA) (Press release, Genmab, JUL 19, 2019, View Source [SID1234537615]). This application seeks approval for the use of the subcutaneous (SubQ) formulation of daratumumab in multiple myeloma indications where the intravenous formulation of daratumumab is currently approved. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"Janssen has now submitted applications for approval of the subcutaneous formulation of daratumumab in both the U.S. and in Europe and we are looking forward to the possibility of multiple myeloma patients in both regions having access to this more convenient formulation of DARZALEX, which allows for both faster dosing and fewer infusion-related reactions according to recently presented data from the COLUMBA study," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The submission is based on data from two ongoing studies: the Phase III non-inferiority COLUMBA study, which is comparing the subcutaneous formulation of daratumumab to the intravenous formulation in patients with relapsed or refractory multiple myeloma and preliminary non-public data from the Phase II PLEIADES study, which is evaluating daratumumab in combination with certain standard multiple myeloma regimens. The topline results from the COLUMBA data were announced in February 2019 and subsequently presented in oral sessions at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the 24th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

About the COLUMBA (MMY3012) study
The Phase III trial (NCT03277105) is a randomized, open-label, parallel assignment study that includes 522 adults diagnosed with relapsed and refractory multiple myeloma. Patients were randomized to receive either: SubQ daratumumab, as 1800 mg daratumumab with rHuPH20 2000 U/mL once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study; or 16 mg/kg IV daratumumab once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The co-primary endpoints of the study are overall response rate and Maximum trough concentration of daratumumab (Ctrough; defined as the serum pre-dose concentration of daratumumab on Cycle 3 Day 1).

About the PLEIADES (MMY2040) study
The Phase II trial (NCT03412565) is a non-randomized, open-label, parallel assignment study that includes 240 adults either newly diagnosed or with relapsed or refractory multiple myeloma. Patients with newly diagnosed multiple myeloma are being treated with 1,800 mg subcutaneous daratumumab in combination with either bortezomib, lenalidomide and dexamethasone (D-VRd) or bortezomib, melphalan and prednisone (D-VMP). Patients with relapsed or refractory multiple myeloma are being treated with 1,800 mg subcutaneous daratumumab plus lenalidomide and dexamethasone (D-Rd). An additional cohort of patients with relapsed and refractory multiple myeloma treated with daratumumab plus carfilzomib and dexamethasone (D-Kd) was subsequently added to the study. The primary endpoint for the D-VMP, D-Kd and D-Rd cohorts is overall response rate. The primary endpoint for the D-VRd cohort is very good partial response or better rate.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis, NKT-cell lymphoma and B-cell and T-cell ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

On July 19, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson is reported with the recent announcement from the World Health Organisation (WHO) to include abiraterone acetate (ZYTIGA) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), in the updated Essential Medicines List, published on 9th July 2019.1,2 (Press release, Johnson & Johnson, JUL 19, 2019, View Source [SID1234537634])

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The WHO’s Essential Medicines List is a core guidance document that helps countries prioritise critical health products that are recommended to be widely available and affordable throughout health systems.1

"The inclusion of abiraterone acetate in the WHO Essential Medicines List highlights the critical role that this treatment can play in improving the lives of patients living with mCRPC and their families," said Dr. Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. "I am proud that we are working hard to impact survival and quality of life by developing and providing innovative medicines which are supported by the highest quality scientific evidence."

The foundation of Janssen’s scientific understanding in prostate cancer is based on the knowledge acquired through the development of innovative treatment options for mCRPC. Abiraterone acetate is an oral androgen biosynthesis inhibitor that is approved for the treatment of both mCRPC and metastatic hormone-sensitive prostate cancer, in Europe.3,4

"The addition of abiraterone acetate to the Essential Medicines List is a significant milestone for Janssen Oncology, reflecting the tireless efforts in recent years to bring optimal treatment options to patients with mCRPC," said Biljana Naumovic, Vice President Commercial Strategy Lead Oncology for Europe, Middle East & Africa, Cilag GmbH International. "This direction from the WHO further emphasises that our work is not yet over. It is critical that patients with prostate cancer have access to treatments that their clinicians feel can benefit them and that we continue to support the prostate cancer community in our common goal of making cancer a manageable and potentially one day, a curable condition."

On July 19, 2019 Genmab A/S (CSE: GEN, Nasdaq: GMAB) reported the exercise in full by the underwriters of their over-allotment option in connection with its initial public offering of American Depositary Shares ("ADSs") in the United States (the "Offering") and the listing of the ADSs on the Nasdaq Global Select Market (Press release, Genmab, JUL 19, 2019, View Source [SID1234537616]). On July 18, 2019, BofA Merrill Lynch, Morgan Stanley and Jefferies, on behalf of the underwriters, notified Genmab of the underwriters’ exercise in full of their previously announced option to purchase up to 4,275,000 additional ADSs, representing 427,500 ordinary shares, to cover any over-allotments (the "Option") at a price of $17.75 per ADS, corresponding to a subscription price of DKK 1,181.80 per underlying ordinary share at an exchange rate of DKK 6.6580 per US$1.00 on July 17, 2019, multiplied by the ADS-to-share ratio of 10 to 1.

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The exercise of the Option will increase the total gross proceeds of the Offering to $581,756,250 (DKK 3,873.3 million) and will result in a total issuance of 32,775,000 ADSs, representing 3,277,500 ordinary shares.

The 427,500 additional shares will be delivered by Genmab in the form of new shares with a nominal value of DKK 1 each (the "New Shares").

Following the registration of the New Shares with the Danish Business Authority, which is expected to take place on July 23, 2019 or early thereafter (and presuming that the 2,850,000 new ordinary shares of a nominal value of DKK 1 that were offered during the Offering will be registered with the Danish Business Authority on July 22, 2019) Genmab’s share capital will amount to DKK 64,967,643 divided into 64,967,643 shares with a nominal value of DKK 1 each.

The New Shares will rank pari passu with Genmab’s existing shares and carry the same dividend and other rights.

The New Shares are expected to be issued and registered with the Danish Business Authority on July 23, 2019 (or early thereafter) and are expected to be admitted to trading and official listing on Nasdaq Copenhagen on July 24, 2019 (or early thereafter), with the permanent ISIN code DK0010272202.

BofA Merrill Lynch, Morgan Stanley and Jefferies are acting as joint book-running managers for the Offering. Guggenheim Securities and RBC Capital Markets are acting as joint lead-managers and Danske Markets, H.C. Wainwright & Co. and Kempen are acting as co-managers for the Offering. A copy of the preliminary prospectus and, when available, the final prospectus relating to the Offering may be obtained from BofA Merrill Lynch, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department, or by email: [email protected]; Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014; or Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone: 1-877-821-7388, or by email: [email protected]. Copies of the preliminary prospectus and, when available, the final prospectus related to the Offering are also available, or will be available, at www.sec.gov. No Danish prospectus will be issued or offered.
This Company Announcement does not constitute an offer to sell nor a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On July 19, 2019 Accuray Incorporated (NASDAQ: ARAY) reported that it will report results for its fourth quarter and fiscal year 2019 ended June 30, 2019 on Thursday, August 15, 2019 after the market close (Press release, Accuray, JUL 19, 2019, View Source [SID1234537635]). Management will host a conference call to review the results at 1:30 p.m. PT/4:30 p.m. ET on the same day.

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The conference call dial-in numbers are 855-867-4103 (USA) or 262-912-4764 (International). In addition, a dial up replay of the conference call will be available approximately one hour after the call’s conclusion for one week. The replay number is 855-859-2056 (USA), or 404-537-3406 (International), Conference ID: 3297842.

A live webcast of the call will also be available from the Investor Relations section of the Company’s website at investors.accuray.com. A webcast replay can be accessed on the website and will remain available until Accuray announces its results for the first quarter of fiscal 2020.

On July 18, 2019 Novartis reported an exceptional first half performance in 2019 as a focused medicines company with strong sales and productivity driving double digit core operating income growth with margin expansion (Press release, Novartis, JUL 18, 2019, https://www.novartis.com/news/media-releases/novartis-delivers-strong-sales-double-digit-core-operating-income-growth-and-launches-zolgensma-and-piqray-second-quarter-sales-and-profit-guidance-increased [SID1234537585]). We increased our full year guidance for both sales and core operating income in light of our strong momentum. We continue to progress our breakthrough medicines pipeline, with the launches of Zolgensma and Piqray, and are on track for the upcoming pivotal trial results of Entresto in preserved ejection fraction heart failure, ofatumumab in multiple sclerosis, and fevipiprant in asthma."

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Financials

In order to comply with International Financial Reporting Standards (IFRS), Novartis has separated the Group’s reported financial data for the current and prior years into "continuing" and "discontinued" operations. The results of the Alcon business are reported as discontinued operations. See page 42 and Notes 2, 3 and 11 in the Condensed Interim Financial Report for a full explanation.

The commentary below focuses on continuing operations including the businesses of Innovative Medicines and Sandoz (including the US generic oral solids and dermatology portfolio), as well as the continuing Corporate functions. We also provide information on discontinued operations.

Continuing operations second quarter

Net sales were USD 11.8 billion (+4%, +8% cc) in the second quarter driven by volume growth of 10 percentage points (cc), mainly from Cosentyx, Entresto and Lutathera. Strong volume growth was partly offset by the negative impacts of pricing (-1 percentage point cc) and generic competition (-1 percentage point cc).

Operating income was USD 2.7 billion (+10%, +17% cc) mainly driven by higher sales, improved gross margin, productivity programs and higher divestment gains, partly offset by growth investments and legal provisions.

Net income was USD 2.1 billion, declining compared to prior year which benefited from a USD 5.7 billion net gain recognized from the sale of our stake in the GSK consumer healthcare joint venture. EPS was USD 0.91.

Core operating income was USD 3.6 billion (+14%, +20% cc) mainly driven by higher sales, improved gross margin and productivity programs, partly offset by growth investments. Core operating income margin was 31.0% of net sales, increasing by 2.7 percentage points (+3.2 percentage points cc).

Core net income was USD 3.1 billion (+13%, +19% cc) driven by growth in core operating income. Core EPS was USD 1.34 (+14%, +20% cc) in line with core net income.

Free cash flow from continuing operations amounted to USD 3.6 billion (+11% USD) compared to USD 3.3 billion in prior year, mainly driven by higher operating income adjusted for non-cash items, and higher divestment proceeds, partly offset by higher working capital, increased payments out of provisions and lower dividends received from the OTC JV which was divested in Q2 2018.

Innovative Medicines net sales were USD 9.3 billion (+5%, +9% cc) in the second quarter, as Pharmaceuticals grew 10% (cc) and Oncology grew 9% (cc). Volume contributed 10 (cc) percentage points to sales growth, mainly driven by Cosentyx, Entresto and Lutathera. Generic competition had a negative impact of 1 (cc) percentage point. Net pricing had a negligible impact.

Sandoz net sales were USD 2.4 billion (-1%, +3% cc) driven by volume growth of 10 percentage points (cc) partially offset by 7 percentage points (cc) of price erosion, mainly in the US. Excluding the US, net sales grew +7% (cc). Global sales of Biopharmaceuticals grew 16% (cc), driven by continued strong double-digit growth in Europe from Rixathon (rituximab), Hyrimoz (adalimumab) and Erelzi (etanercept).

Novartis continues to expect the previously-announced divestment of the Sandoz US oral solids and dermatology portfolio to be completed during 2019, pending closing conditions including regulatory approvals. Novartis remains fully committed to this business until it is divested to Aurobindo. The results of this business are included in continuing operations.

Continuing operations first half

Net sales were USD 22.9 billion (+3%, +8% cc) in the first half driven by volume growth of 11 percentage points (cc), mainly from Cosentyx, Entresto and Lutathera. Strong volume growth was partly offset by the negative impacts of pricing (-2 percentage points cc) and generic competition (-1 percentage point cc).

Operating income was USD 4.9 billion (+2%, +11% cc) mainly driven by higher sales and improved gross margin, partly offset by growth investments and legal provisions.

Net income was USD 4.0 billion (-59%, -56% cc) as prior year benefited from a USD 5.7 billion net gain recognized from the sale of our stake in the GSK consumer healthcare joint venture. EPS was USD 1.72 (-59%, -55% cc) in line with net income.

Core operating income was USD 6.9 billion (12%, +19% cc) mainly driven by higher sales, improved gross margin and productivity programs, partly offset by growth investments. Core operating income margin was 30.2% of net sales, increasing by 2.4 percentage points (+2.9 percentage points cc).

Core net income was USD 5.9 billion (+9%, +16% cc) driven by growth in core operating income partly offset by the discontinuation of core income from the GSK consumer healthcare joint venture. Core EPS was USD 2.55 (+9%, +17% cc) in line with core net income.

Free cash flow from continuing operations amounted to USD 5.5 billion (+6% USD) compared to USD 5.2 billion in the prior year, mainly driven by higher operating income adjusted for non-cash items, and higher divestment proceeds, partly offset by higher working capital, a sales milestone from the divested Vaccines business received in the prior year, increased payments out of provisions and lower dividends received from the OTC JV which was divested in Q2 2018.

Innovative medicines delivered net sales of USD 18.1 billion (+5%, +10% cc) in the first half. Pharmaceuticals BU grew 10% (cc) driven by Cosentyx and Entresto. Oncology grew 9% (cc) driven by Lutathera, as well as Promacta/Revolade, Tafinlar + Mekinist and Kisqali. Volume contributed 11 (cc) percentage points to sales growth. Generic competition had a negative impact of 1 (cc) percentage point. Net pricing had a negligible impact.

Sandoz net sales were USD 4.8 billion (-4%, +1% cc) driven by volume growth of 9 percentage points (cc) partially offset by 8 percentage points (cc) of price erosion, mainly in the US. Excluding the US, net sales grew 6% (cc). Global sales of Biopharmaceuticals grew 14% (cc), driven by continued strong double-digit growth in Europe from Rixathon (rituximab), Hyrimoz (adalimumab) and Erelzi (etanercept).

Discontinued operations second quarter

Discontinued operations include the business of Alcon and certain Corporate costs directly attributable to Alcon up to the spin-off date. As the Alcon spin-off was completed on April 9, 2019, the operating results in the second quarter were not material. Net income in the second quarter 2019 includes the non-taxable non-cash net gain on distribution of Alcon Inc. to Novartis AG shareholders which amounted to USD 4.7 billion. The second quarter of prior year included the results from the operations of the Alcon Division and certain Corporate costs directly attributable to Alcon with sales of USD 1.8 billion and operating income of USD 53 million. For further details see Note 3 Significant transactions – Completion of the spin-off of the Alcon business through a dividend in kind distribution to Novartis shareholders.

Discontinued operations first half

Discontinued operations net sales in the first half of 2019 were USD 1.8 billion compared to USD 3.6 billion in 2018 and operating income amounted to USD 71 million compared to USD 129 million in 2018. Net income from discontinued operations in the first half of 2019 amounted to USD 4.6 billion compared to USD 98 million in 2018 driven by the non-taxable non-cash net gain on distribution of Alcon Inc. to Novartis AG shareholders which amounted to USD 4.7 billion. For further details see Note 3 Significant transactions – Completion of the spin-off of the Alcon business through a dividend in kind distribution to Novartis shareholders.

Total Group second quarter

For the total Group, net income amounted to USD 6.8 billion compared to USD 7.8 billion in the prior year, and basic earnings per share decreased to USD 2.94 from USD 3.34. Cash flow from operating activities for the total Group amounted to USD 3.1 billion and free cash flow to USD 3.6 billion.

Total Group first half

For the total Group, net income amounted to USD 8.6 billion compared to USD 9.8 billion in the prior year, and basic earnings per share decreased to USD 3.70 from USD 4.21. Cash flow from operating activities for the total Group amounted to USD 5.5 billion and free cash flow to USD 5.4 billion.

ECN Appointment

Novartis has appointed Marie-France Tschudin as president of Novartis Pharmaceuticals. She is a member of the Executive Committee of Novartis and reports to Vas Narasimhan, CEO, Novartis.

Marie-France Tschudin has more than 25 years of broad, multi-national experience in the pharmaceuticals and biotech industry. She was most recently Head of Novartis Pharmaceuticals, Region Europe where she successfully grew the largest regional business within Novartis to over USD 8 billion in sales in 2018. She also built a diverse leadership team and oversaw the preparations for our potential blockbuster launches in Europe. Before joining Novartis, Marie-France spent 10 years at Celgene in a variety of leadership and general management positions and led their Hematology-Oncology business for Europe, Middle East and Africa.

Key growth drivers (Q2 performance)

Underpinning our financial results in the second quarter is a continued focus on key growth drivers including:

Cosentyx (USD 858 million, +25% cc) delivered strong demand driven growth in the US and all other regions. In the US, Cosentyx (USD 534 million) sales grew 31%, in the rest of the world sales grew 18% (cc).
Entresto (USD 421 million, +81% cc) delivered a strong quarter with continued growth momentum fueled by increased demand in both hospital and ambulatory settings across all territories/geographies. The Heart Failure Association of the European Society of Cardiology published a consensus paper in May that supports Entresto as a first line treatment option for patients hospitalized with HFrEF.
Lutathera (USD 109 million, USD +85 million) continued to grow led by the US with over 140 centers actively treating and the European launch progressing well. Sales from all AAA brands (including Lutathera and radiopharmaceutical diagnostic products) were USD 171 million.
Promacta/Revolade (USD 349 million, +23% cc) continued to grow at a strong double-digit rate across all regions driven by increased use in chronic immune thrombocytopenia (ITP) and uptake as first-line treatment for severe aplastic anemia (SAA) in the US and Japan.
Tafinlar + Mekinist (USD 340 million, +25% cc) continued double-digit growth due to demand in metastatic melanoma and NSCLC, and strong uptake of the adjuvant melanoma indication in the US and Europe.
Jakavi (USD 284 million, +26% cc) continued double-digit growth across all regions driven by demand in myelofibrosis and polycythemia vera indications.
Kisqali (USD 111 million, +94% cc) continued to grow in the US driven by use in first-line metastatic breast cancer patients, independent of menopausal status or combination partner, with strong uptake in Europe and other regions.
Kymriah (USD 58 million) strong demand continued and sales increased primarily driven by ongoing uptake in the US and Europe. There are over 130 qualified treatment centers and 19 countries worldwide that have coverage for at least one indication. Reimbursement for both Pediatric ALL and DLBCL was received in Japan, making Kymriah the only CAR-T available in Asia.
Biopharmaceuticals (biosimilars, biopharmaceutical contract manufacturing and Glatopa) grew 16% (cc), driven by continued strong double-digit growth in Europe from Rixathon (rituximab), Hyrimoz (adalimumab) and Erelzi (etanercept).
Emerging Growth Markets, which comprise all markets except the US, Canada, Western Europe, Japan, Australia and New Zealand, sales grew 9% in cc (1% in USD), mainly driven by double digit growth (cc) in China.

Strengthen R&D – Key developments from the second quarter

New approvals and regulatory update

Zolgensma (onasemnogene abeparvovec-xioi) was launched in the US following FDA approval. Zolgensma is approved for the treatment of patients less than 2 years of age with SMA and bi-allelic mutations of the SMN1 gene, regardless of SMN2 back-up gene copy number (all types). This also includes pre-symptomatic newborns who are diagnosed by genetic testing.
Piqray (alpelisib, formerly BYL719) was approved and launched in the US as the first and only treatment specifically for patients with a PIK3CA mutation in HR+/HER2- advanced breast cancer. Piqray was the first new drug application approved under the FDA Oncology Center of Excellence Real-Time Oncology Review pilot program.
Regulatory submissions and filings

Crizanlizumab (SEG101) was filed in the US and Europe for the prevention of vaso-occlusive crises in sickle cell disease. Crizanlizumab received priority review designation from the FDA in July.
QVM149 (ICS/LABA/LAMA) and QMF149 (ICS/LABA) were both filed with EMA for the treatment of asthma. QVM149 has the potential to become the best in class inhaled treatment by adding the power of comprehensive bronchodilation to on-target inflammation control with a once-daily inhalation.
Results from ongoing trials and other highlights

Zolgensma data were presented at AAN demonstrating efficacy in broad a spectrum of SMA patients:
STRONG trial interim data in SMA Type 2 showed rapid motor function gains and milestone achievements with intrathecal dosing
SPR1NT interim data in pre-symptomatic SMA showed age-appropriate motor milestone achievement
STR1VE interim data in SMA Type 1 continued to show event-free survival, increases in motor function and significant milestone achievement consistent with Phase 1 START trial
Kisqali MONALEESA-7 overall survival data were presented at ASCO (Free ASCO Whitepaper) in first-line treatment of advanced breast cancer exclusively in peri- and premenopausal women. The data showed a survival rate of 70.2% for patients on Kisqali combination therapy compared to 46.0% for endocrine therapy alone. Kisqali is the only CDK4/6 inhibitor to show superior overall survival in advanced breast cancer.
Capmatinib (INC280) GEOMETRY mono-1 Phase II data in patients with NSCLC that harbor MET exon-14 skipping mutation were presented at ASCO (Free ASCO Whitepaper). The overall response rate among patients receiving capmatinib was 68% for treatment-naive and 41% for previously treated patients. The median duration of response was also clinically meaningful irrespective of prior line of therapy.
Mayzent (siponimod) data from EXPAND study, presented at AAN, demonstrated that treatment had a clinically meaningful positive impact on cognitive processing speed in patients with secondary progressive MS, an important element in cognitive function. These data supplement benefits seen in terms of delay in disability progression in this population.
Iscalimab (CFZ533) data were presented at the American Transplant Congress showing 60% of iscalimab-treated transplant patients have normal kidney histology at least 1 year after transplant vs 0% with tacrolimus (current standard of care).
Cosentyx FUTURE 5 and MAXIMISE data were presented at EULAR. FUTURE 5 reinforced that there was no radiographic progression in almost 90% of psoriatic arthritis (PsA) patients treated over 2 years. MAXIMISE showed first efficacy and safety of a biologic treatment in the management of axial manifestations of PsA, which affect up to an estimated 35 million people worldwide.
Tafinlar + Mekinist overall survival data presented at ASCO (Free ASCO Whitepaper) and published simultaneously in NEJM, showed in patients with unresectable or metastatic BRAF-mutation positive melanoma, 34% of all patients in the pooled COMBI-d and COMBI-v trial analysis survived at five years. Nineteen percent of patients also showed no sign of disease progression or death at five years.
Hyrimoz (Sandoz biosimilar adalimumab) Phase III ADMYRA trial data presented at EULAR confirmed switching from reference biologic had no impact on safety or efficacy in patients with moderate-to-severe rheumatoid arthritis.
Capital structure and net debt
Retaining a good balance between investment in the business, a strong capital structure and attractive shareholder returns remains a priority.

During the first half of 2019, Novartis repurchased a total of 32.8 million shares for USD 2.8 billion on the SIX Swiss Exchange second trading line, including 19.0 million shares (USD 1.7 billion) bought back under the up to USD 5 billion share buyback announced in June 2018 and 13.8 million shares (USD 1.1 billion) to mitigate dilution related to participation plans of associates. In addition, 1.6 million shares (USD 0.2 billion) were repurchased from associates. In the same period, 15.0 million shares (for an equity value of USD 0.7 billion) were delivered as a result of options exercised and share deliveries related to participation plans of associates. Consequently, the total number of shares outstanding decreased by 19.4 million versus December 31, 2018. These treasury share transactions resulted in a decrease in equity of USD 2.3 billion and a net cash outflow of USD 2.4 billion (excluding Swiss Withholding Tax of USD 0.4bn on share buybacks to be paid in Q3 2019).

A total of 28.3 million shares have been purchased for a total of USD 2.5 billion under the up to USD 5 billion share buyback since its announcement in June 2018. This share buyback is expected to be completed by the end of 2019.

As of June 30, 2019, net debt increased by USD 1.7 billion to USD 17.9 billion versus December 31, 2018. The increase was mainly driven by the USD 6.6 billion annual dividend payment and the net cash outflow for treasury share transactions of USD 2.4 billion, partly offset by USD 5.5 billion free cash flow from continuing operations during the first half of 2019 and USD 2.9 billion net inflows related to the Alcon spin-off.

As of Q2 2019, the long-term credit rating for the company is A1 with Moody’s Investors Service and AA- with S&P Global Ratings.

2019 Outlook

Barring unforeseen events

New focused medicines company guidance
Excluding Alcon and the Sandoz US oral solids and dermatology business from both 2018 and 2019

Net sales revised upwards: expected to grow mid to high-single digit (cc).
From a divisional perspective, we expect net sales performance (cc) in 2019 to be as follows:
Innovative Medicines revised upwards: grow mid to high-single digit
Sandoz revised upwards: broadly in line to low-single digit growth
Core operating income revised upwards: expected to grow low double digit to mid-teens (cc).
The guidance above includes the forecast assumption that no Gilenya generics enter in 2019 in the US.

Foreign Exchange impact

If mid-July exchange rates prevail for the remainder of 2019, the currency impact for the year would be negative 3 percentage points on net sales and negative 4 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.