Net sales up 1% (cc[1]), as Growth Products offset Gleevec impact

Growth Products[2] grew 24% (USD) to USD 3.9 billion, or 34% of Group net sales

Cosentyx (USD 176 million) continues to grow strongly, benefitting from long-term efficacy data for psoriasis and new launches in AS and PsA[3]

Entresto (USD 17 million) launch continues to accelerate in EU, field force ramping up in US

Core[1] operating income declines (-5% cc), driven by generic erosion and growth investments

Marketing & Sales expense up 1.1 percentage points to 23.6% of sales behind new launches

Core operating income margin declined 1.8 percentage points (cc)

Core EPS of USD 1.17, down 5% (cc)

Free cash flow[1] of USD 1.4 billion

Continued to build the pipeline in Q1

Afinitor received FDA approval for progressive, nonfunctional GI/lung NET

New analysis of PARADIGM-HF data reinforces benefit of Entresto to clinically stable patients

Cosentyx data in psoriasis showed superiority to Stelara in sustaining skin clearance at 52 weeks

Acquired exclusive ex-US rights to research, develop and commercialize Jakavi in GVHD

Sandoz acquired rights to biosimilar infliximab in Europe

Alcon acquired Transcend Medical, strengthening its Surgical glaucoma pipeline

Group-wide initiatives and Alcon growth plan on track

Transferred operational control for Ophthalmic Pharmaceuticals from Alcon to Pharmaceuticals Division and selected mature products from Pharmaceuticals Division to Sandoz

Alcon growth plan on track, with steps taken to accelerate innovation and sales, strengthen customer relationships and improve basic operations

Centralization of manufacturing and integration of drug development on track for July 1, 2016 implementation; expected annual
cost savings of USD 1 billion by 2020 confirmed

2016 Outlook confirmed:

Net sales and core operating income expected to be broadly in line with prior year (cc)
Key figures [1] Continuing operations[4]
Q1 2016 Q1 2015 % change
USD m USD m USD cc
Net sales 11 600 11 935 -3 1
Operating income 2 451 2 785 -12 -5
Net income 2 011 2 306 -13 -4
EPS (USD) 0.85 0.96 -11 -3
Free cash flow 1 362 1 465 -7
Core
Operating income 3 261 3 651 -11 -5
Net income 2 788 3 199 -13 -6
EPS (USD) 1.17 1.33 -12 -5
[1] Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 39 of the Condensed Interim Financial Report. Unless otherwise noted, all growth rates in this Release refer to same period in prior year.
[2] Growth Products are defined on page 2.
[3] Ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
[4] Refers to continuing operations, defined on page 32 of the Condensed Interim Financial Report.


On April 21, 2016 Novartis reported that they had a solid Q1 despite Gleevec loss of exclusivity (Press release, Novartis, APR 21, 2016, View Source [SID:1234511224]).

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Commenting on the results, Joseph Jimenez, CEO of Novartis, said: "I am pleased we were able to show sales growth in constant currencies despite the entry of a generic version of Gleevec in the US. As expected, our results reflect additional investments behind our new launches and Alcon. We are on track with the plan we outlined in January to further focus our divisions, drive greater innovation and significant synergies and productivity. I remain confident in our long-term growth prospects, underpinned by our strong pipeline and the talent leading our Research and Development functions."

GROUP REVIEW

Novartis laid out five priorities for 2016: deliver strong financial results; strengthen innovation; improve Alcon performance; capture cross-divisional synergies; and build a higher-performing organization. We made progress in each of these areas in the first quarter.

Financial results

On January 27, 2016, Novartis announced plans to further focus our divisions, integrating businesses that share therapeutic areas to better leverage our development and marketing capabilities. These plans included the transfer of the Ophthalmic Pharmaceuticals franchise from Alcon to the Pharmaceuticals Division, and the transfer of selected mature products from the Pharmaceuticals Division to Sandoz. Operationally, these transfers were completed as of April 1, 2016. The centralization of manufacturing and integration of some drug development functions, also announced on January 27, 2016, are on track for implementation by July 1, 2016.

In compliance with International Financial Reporting Standards (IFRS), Novartis updated its segment financials to reflect the new divisional structure, both for the current and prior year, to aid comparability of year-on-year results. As a result, all comparisons of divisional results from 2016 to 2015 reflect this new divisional structure.

In addition, in 2015, Novartis completed a series of portfolio transformation transactions, including the acquisition of oncology assets from GSK and a 36.5% interest in GSK Consumer Healthcare Holdings, and the divestment of its Vaccines and Animal Health businesses. To reflect these transactions, Novartis reported the Group’s financial results in 2015 as "continuing operations" and "discontinued operations." All comparisons from 2016 to 2015 are versus continuing operations, unless otherwise noted. See page 32 of the Condensed Interim Financial Report for a full explanation.

First quarter

Continuing operations

Net sales were USD 11.6 billion (-3%, +1% cc) in the first quarter, as volume growth of 7 percentage points more than offset the negative impact of generic competition (-4 percentage points) and pricing (-2 percentage points). Growth Products[1] contributed USD 3.9 billion or 34% of net sales, up 24% (USD) over the prior-year quarter.

Operating income was USD 2.5 billion (-12%, -5% cc). Core adjustments amounted to USD 0.8 billion (2015: USD 0.9 billion), with product divestment gains partly offset by amortization of the oncology assets acquired from GSK in Pharmaceuticals.

Core operating income was USD 3.3 billion (-11%, -5% cc). Core operating income margin in constant currencies decreased 1.8 percentage points, mainly due to loss of exclusivity on Gleevec, investments behind new launches and the Alcon growth plan. Currency had a negative impact of 0.7 percentage points, resulting in a net decrease of 2.5 percentage points in US dollar terms to 28.1% of net sales.

Net income was USD 2.0 billion (-13%, -4% cc), broadly in line with operating income.

EPS was USD 0.85 (-11%, -3% cc), broadly in line with net income.

Core net income was USD 2.8 billion (-13%, -6% cc), broadly in line with core operating income.

Core EPS was USD 1.17 (-12%, -5% cc), broadly in line with core net income.

Free cash flow was USD 1.4 billion (USD -0.1 billion), broadly in line with the prior-year quarter.

Pharmaceuticals net sales were USD 7.7 billion (-3%, +1% cc) in the first quarter, with volume growth of 9 percentage points. Generic competition had a negative impact of 6 percentage points and pricing had a negative impact of 2 percentage points, both largely due to Gleevec/Glivec genericization in the US. Growth Products generated USD 3.3 billion or 42% of division net sales. These products grew 31% (cc) over the same period last year. The oncology assets acquired from GSK continued to contribute significantly to sales growth in the quarter, as the prior-year period only included one month of sales (due to closing of the transaction on March 2, 2015). Generic impact on the Ophthalmic Pharmaceuticals products transferred from Alcon, mainly Patanol, negatively impacted Pharmaceuticals sales growth in the quarter.

Operating income was USD 2.2 billion (-11%, -4% cc). Core operating income was USD 2.6 billion (-9%, -3% cc). Core operating income margin in constant currencies decreased by 1.5 percentage points, driven by higher production costs and launch investments in Entresto and Cosentyx. Currency had a negative impact of 0.7 percentage points, resulting in a net decrease of 2.2 percentage points to 33.7% of net sales.

Sandoz net sales were USD 2.4 billion (0%, +4% cc) in the first quarter, as volume growth of 11 percentage points more than offset 7 percentage points of price erosion. Global sales of Biopharmaceuticals grew 50% (cc) to USD 214 million, benefitting from the launches of Glatopa in June 2015 and Zarxio in September 2015. Anti-Infectives franchise sales were USD 360 million (-3% cc), reflecting the weak flu season compared to the prior year. The mature products transferred from the Pharmaceuticals Division grew versus prior year (cc), benefitting from four products which were part of the oncology assets acquired from GSK.

Operating income was USD 346 million (+2%, +9% cc). Core operating income was USD 485 million (0%, +6% cc). Core operating income margin in constant currencies increased by 0.5 percentage points, with a positive impact from the mature products and ongoing productivity improvements, and a negative impact from higher M&S investment behind biosimilars and other key products. Currency had a negative impact of 0.5 percentage points, resulting in a core operating income margin of 19.8% of net sales.

Alcon net sales were USD 1.4 billion (-7%, -3% cc) in the first quarter. Surgical sales (-3% cc) were driven by a slowdown in cataract equipment placements, as we progress through the launch cycles for Centurion and LenSx. Cataract consumables delivered growth, more than offsetting a slight decline in intraocular lenses (IOLs). Vision Care performance (-4% cc) was impacted by weaker sales of AirOptix and Dailies AquaComfort Plus in the US, despite continued strong sales of Dailies Total1 globally. Contact lens care declined due to competitive pressure and the continued market shift to daily disposable lenses.

Operating income was USD 31 million (-78%, -52% cc). Core operating income was USD 243 million (-36%, -26% cc), primarily impacted by declining sales and our planned higher spending in M&S behind the growth plan. Core operating income margin in constant currencies decreased by 5.9 percentage points; currency had a negative impact of 2.1 percentage points, resulting in a net decrease of 8.0 percentage points to 17.0% of net sales.

Total Group

For the total Group, net income amounted to USD 2.0 billion compared to USD 13.0 billion in the prior-year period, and basic earnings per share decreased to USD 0.85 from USD 5.40. The decrease was due to the income from discontinued operations, which in the prior-year period included USD 12.8 billion exceptional divestment gains from the portfolio transformation transactions and USD 0.5 billion additional transaction related expenses.

Free cash flow was USD 1.4 billion compared to USD 1.2 billion in the first quarter of 2015.

[1] Growth Products" are an indicator of the rejuvenation of the portfolio, and comprise products launched in a key market (EU, US, Japan) in 2011 or later, or products with exclusivity in key markets until at least 2020 (except Sandoz, which includes only products launched in the last 24 months). They include the acquisition effect of the GSK oncology assets.

Key growth drivers

Underpinning our financial results in the first quarter is a continued focus on key growth drivers, including Gilenya, Tasigna, Cosentyx, Tafinlar + Mekinist, Jakavi, Promacta/Revolade and Entresto, as well as Biopharmaceuticals and Emerging Growth Markets.

Growth Products

Growth Products, an indicator of the ongoing rejuvenation of our portfolio, contributed 34% of Group net sales in the first quarter, and were up 24% (USD). In Pharmaceuticals, Growth Products contributed 42% of division net sales in the quarter, and sales for these products were up 31% (cc).

Gilenya (USD 698 million, +12% cc), our oral MS therapy, grew double-digit in the quarter behind strong volume growth.

Tasigna (USD 382 million, +6% cc) continued to grow globally and in the US, despite the entry of a generic version of Gleevec in the US market on February 1, 2016.

Cosentyx(USD 176 million), which was launched in the first quarter of 2015 as the first fully human IL-17A inhibitor for the treatment of psoriasis, continued to show strong growth and accelerated uptake in the first quarter of 2016, benefitting from its three approved indications (psoriasis, ankylosing spondylitis and psoriatic arthritis).

Tafinlar + Mekinist (USD 150 million) grew as the first approved combination therapy for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Promacta/Revolade (USD 131 million) performance was driven by continued growth in the chronic immune (idiopathic) thrombocytopenic purpura (ITP) indication worldwide.

Jakavi (USD 124 million, +44% cc), an oral JAK inhibitor approved for myelofibrosis and polycythemia vera, continued to grow strongly over the previous-year quarter.

Entresto (USD 17 million), our breakthrough treatment for chronic heart failure with reduced ejection fraction, saw formulary access improve in the US. 91% of Medicare patients now have access, with 65% at the lowest branded co-pay by plan. Starting in April, the US field force is being expanded and a direct-to-consumer campaign is being launched. Early experience in Europe has also been encouraging, with better early access and a more rapid uptake. Entresto sales are expected to be approximately USD 200 million for full year 2016.

Biopharmaceuticals (which include biosimilars, biopharmaceutical contract manufacturing and Glatopa) grew 50% (cc) to USD 214 million, benefitting from the launches of Glatopa in June 2015 and Zarxio in September 2015.
Emerging Growth Markets

Net sales in Emerging Growth Markets – which comprise all markets except the US, Canada, Western Europe, Japan, Australia and New Zealand – grew 5% (cc) in the first quarter, led by Brazil (+17% cc) and Turkey (+19% cc).
Strengthen innovation

The first quarter saw pipeline progress with positive regulatory decisions and significant clinical trial data released. Key developments are included below.

New approvals and positive opinions

The FDA approved Afinitor (everolimus) for use in advanced, progressive, nonfunctional neuroendocrine tumors of gastrointestinal or lung origin.

Revolade (eltrombopag) received EU approval as a first-in-class therapy for children aged 1 year and above with chronic ITP.

The EC approved Exjade (deferasirox) film-coated tablets, which can be swallowed whole, for the same indications as Exjade dispersible tablets.

Tafinlar + Mekinist (dabrafenib + trametinib) combination was approved in Japan for the treatment of unresectable melanoma with BRAF mutation.

Zykadia (ceritinib) was approved in Japan for the treatment of patients with ALK-positive non-small cell lung cancer.

Sandoz received EC approval for the subcutaneous administration of biosimilar Binocrit (epoetin alfa) in the nephrology indication.
Regulatory submissions and filings

The EMA accepted Sandoz’s regulatory submission for biosimilar Neulasta(pegfilgrastim), marking the division’s fifth of 10 planned biosimilar filings through 2017.
Results from important clinical trials and other highlights

New data from the head-to-head CLEAR study showed that Cosentyx (secukinumab) remains superior to Stelara in sustaining skin clearance (PASI 90 to PASI 100) at 52 weeks for adults with moderate-to-severe psoriasis.

New analyses from the PARADIGM-HF trial showed Entresto (sacubitril/valsartan) reduces cardiovascular death and heart failure hospitalizations by 20% compared to ACE inhibitor enalapril, regardless of background therapy and in patients considered clinically stable.

Results from the ATMOSPHERE trial demonstrated no benefit from adding aliskiren, a renin inhibitor, to enalapril. These results suggest that there could be an efficacy ceiling to the renin-angiotensin system (RAS) blockade, which would further reinforce the superiority of Entresto’s novel mechanism of angiotensin receptor blockade/neprilysin inhibition in improving heart failure outcomes versus maximizing the RAS system alone.

Our collaboration and license agreement with Incyte has been amended to grant Novartis exclusive research, development and commercialization rights for Jakavi (ruxolitinib) in graft-versus-host disease (GVHD) outside the US. GVHD is an area of high unmet medical need with no approved treatment options to date.

PKC412 (midostaurin) received FDA Breakthrough Therapy designation for newly-diagnosed FLT3-mutated acute myeloid leukemia (AML). Worldwide regulatory submissions for PKC412 are expected to begin in 2016.

A Phase IIb/III study evaluating BYM338 (bimagrumab) in sporadic inclusion body myositis did not meet its primary endpoint. Novartis is evaluating the complete dataset to inform decisions regarding ongoing development of bimagrumab.

Sandoz acquired the rights for development and commercialization of biosimilar Remicade (infliximab) in the European Economic Area, further strengthening its immunology pipeline, which includes investigational biosimilars adalimumab, etanercept and rituximab.

Alcon strengthened its Surgical pipeline with the acquisition of Transcend Medical, a privately-held company focused on developing minimally-invasive surgical devices to treat glaucoma.
Improve Alcon performance

On January 27, 2016, we outlined delivery milestones for the Alcon turnaround, starting with focusing the division on its core Surgical and Vision Care business. Operational control for the Ophthalmic Pharmaceuticals franchise was transferred on April 1, 2016 to the Pharmaceuticals Division.

Within the newly focused Alcon devices business, we made investments in the first quarter to accelerate innovation and sales, strengthen customer relationships and improve basic operations. We increased M&S in both Surgical and Vision Care, including for new IOL launches and promotional programs behind key contact lens brands. We also initiated multiple projects to improve customer service and supply chain performance.

We expect our investments to improve sales performance later in the year.

Capture cross-divisional synergies

On January 27, 2016, Novartis outlined several initiatives to leverage Group scale to drive even greater efficiency and innovation. These included centralizing our manufacturing operations across divisions within a single Technical Operations unit, and integrating some drug development functions across divisions.

These initiatives are incremental to our existing productivity programs, including synergies delivered by Novartis Business Services (NBS), our cross-divisional services organization, created in 2014 to drive efficiency, standardization and simplification across the Group.

We continued to advance all of our productivity programs in the first quarter, helping to support margins for the group.

NBS continued to execute on its priorities in the first quarter. For example, one source of efficiencies delivered was the consolidation of Facilities Services from more than 100 to three key suppliers globally. In addition, NBS continued to scale up the offshoring of transactional services to its five Global Service Centers, and prepare for the rollout of an in-country commercial and medical support platform (expected to start in the second quarter). The cost within the scope of NBS remained stable from the prior-year quarter.

In Procurement, we generated approximately USD 0.3 billion in savings by leveraging our scale.

We took the first step in centralizing our manufacturing operations in the first quarter with the appointment of Andre Wyss as President, Novartis Operations. The new Technical Operations unit, which aims to optimize capacity planning and lower costs through simplification, standardization and external spend optimization across divisions, is expected to be in place by July 1, 2016. Our manufacturing footprint initiative, which was first launched in 2010, will now be managed by the centralized Technical Operations unit.

We increased Group-wide coordination of drug development with the appointment of Vas Narasimhan as the Global Head of Drug Development to help improve resource allocation, technology and standards across divisions. In the first quarter, we also completed the integration of development for the Ophthalmic Pharmaceuticals franchise, which previously was managed by the Alcon Division.

In total, our productivity initiatives generated gross savings of approximately USD 0.5 billion in the first quarter.

Build a higher-performing organization

The company’s focus on quality continued to yield results in the first quarter of 2016. A total of 32 global health authority inspections were completed and closed during the quarter, nine of which were conducted by the FDA. All 32 closed inspections were deemed good or acceptable. The outcome of an ongoing inspection by the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK is still pending.

Capital structure and net debt

Retaining a good balance between investment in the business, a strong capital structure and attractive shareholder returns will remain a priority. Strong cash flows and a sound capital structure have allowed Novartis to focus on driving innovation and growth across its diversified healthcare portfolio, while keeping its double-A credit rating as a reflection of financial strength and discipline.

During Q1 2016, 12.1 million treasury shares were delivered as a result of options exercised and share deliveries related to equity-based participation plans of associates. To partially offset the dilutive impact related to such transactions, 4.7 million Novartis shares were repurchased on the SIX Swiss Exchange second trading line and from employees. With these transactions, the total number of shares outstanding increased by 7.4 million in the first quarter of 2016. Novartis aims to further offset the dilutive impact from equity-based participation plans of associates experienced in the first quarter over the remainder of the year through additional share purchases.

As of March 31, 2016, the net debt increased by USD 6.5 billion to USD 23.0 billion, compared to USD 16.5 billion at December 31, 2015. The free cash flow of USD 1.4 billion was primarily used for payments related to the acquisition of businesses, share repurchases and the portfolio transformation transactions. The increase in net debt was driven by the dividend payment of USD 6.5 billion.

The long-term credit rating for the company continues to be double-A (Moody’s Aa3; Standard & Poor’s AA-; Fitch AA).

2016 Outlook

Barring unforeseen events

We confirm our outlook as presented at the beginning of 2016. Group net sales and core operating income are expected to be broadly in line with the prior year (cc), after absorbing the impact of generic competition. Generic competition impact on sales is expected to be as much as USD 3.2 billion compared to USD 2.2 billion in 2015.

These comparisons are versus 2015 continuing operations.

If March average exchange rates prevail for the remainder of 2016, the currency impact for the year would be negative 2% on sales and negative 3% on core operating income. This currency impact versus 2015 results from the continued strength of the US dollar against most currencies.

Summary Financial Performance

Continuing operations [1]

Q1 2016 Q1 2015 % change
USD m USD m USD cc
Net sales 11 600 11 935 -3 1
Operating income 2 451 2 785 -12 -5
As % of net sales 21.1 23.3
Core operating income 3 261 3 651 -11 -5
As % of net sales 28.1 30.6
Net income 2 011 2 306 -13 -4
EPS (USD) 0.85 0.96 -11 -3
Free cash flow 1 362 1 465 -7
Pharmaceuticals

Q1 2016 Q1 2015 [2] % change
USD m USD m USD cc
Net sales 7 729 7 960 -3 1
Operating income 2 180 2 450 -11 -4
As % of net sales 28.2 30.8
Core operating income 2 602 2 855 -9 -3
As % of net sales 33.7 35.9
Sandoz

Q1 2016 Q1 2015[2] % change
USD m USD m USD cc
Net sales 2 445 2 444 0 4
Operating income 346 340 2 9
As % of net sales 14.2 13.9
Core operating income 485 483 0 6
As % of net sales 19.8 19.8
Alcon

Q1 2016 Q1 2015[2] % change
USD m USD m USD cc
Net sales 1 426 1 531 -7 -3
Operating income 31 141 -78 -52
As % of net sales 2.2 9.2
Core operating income 243 382 -36 -26
As % of net sales 17.0 25.0
Corporate

Q1 2016 Q1 2015 % change
USD m USD m USD cc
Operating loss -106 -146 27 14
Core operating loss -69 -69 0 -29
Discontinued operations

Q1 2016 Q1 2015 % change
USD m USD m USD cc
Net sales 548
Operating income 12 622
As % of net sales nm
Core operating loss -102
As % of net sales -18.6
Total Group [3]

Q1 2016 Q1 2015 % change
USD m USD m USD cc
Net income 2 011 13 005 -85 -83
EPS (USD) 0.85 5.40 -84 -83
Free cash flow 1 362 1 226 11

[1] Continuing operations include the businesses of Pharmaceuticals, Sandoz and Alcon and starting on March 2, 2015 the results from the oncology assets acquired from GSK and the 36.5% interest in the GSK Consumer Healthcare Holdings (the latter reported as part of income from associated companies). See page 32 of the Condensed Interim Financial Report for full explanation.
[2] In compliance with IFRS, Novartis updated its segment financials to reflect the new divisional structure announced on January 27, 2016, to aid comparability of year-on-year results.
[3] Total Group net income and EPS include in the prior year the impact of the exceptional divestment gains and the operating results of the discontinued operations. Total Group free cash flow comprises the free cash flow from continuing operations and discontinued operations.

A condensed interim financial report with the information listed in the index below can be found on our website at View Source (link is external).

On April 21, 2016 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) reported positive data from preclinical studies evaluating MM-310, an antibody directed nanotherapeutic (ADN) that encapsulates a newly engineered form of the highly potent chemotherapy docetaxel as a prodrug in an ephrin receptor A2 (EphA2)-targeted liposome (Press release, Merrimack, APR 21, 2016, View Source [SID:1234511223]). Preclinical data on MM-310 were presented in an oral presentation and three poster sessions at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The posters can be accessed on Merrimack’s website.

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"We designed MM-310 to deliver a large and sustained chemotherapy payload of Merrimack’s newly engineered docetaxel prodrug within a protective nanoliposome to the tumor site while minimizing exposure to healthy tissues, with a goal of overcoming one of the greatest challenges in cancer treatment," said Walid Kamoun, Ph.D., Research Team Lead at Merrimack. "We also used our systems approach to choose the EphA2 target as a means of enhancing MM-310’s ability to be taken in by tumor cells and to penetrate deep into the tumor core. We are excited by MM-310’s preclinical data set and look forward to future clinical evaluation of this latest therapeutic candidate from our ADN platform."

Key findings show that MM-310 demonstrated superior antitumor activity in multiple models compared to free docetaxel and also showed that EphA2 targeted liposomes entered and delivered the cytotoxic to the tumor cell while minimizing exposure to healthy tissues, significantly decreasing traditional docetaxel drug-related side effects, such as neutropenia, in preclinical models. EphA2 receptors are associated with poor prognosis and are shown to be overexpressed in several solid tumors, including prostate, ovarian, bladder, gastric and lung cancers.

"In an analysis of the docetaxel dose-response relationship, the data strongly suggest that the ability to deliver a higher dose of the traditional chemotherapy may lead to higher therapeutic response but also to higher toxicity. In our preclinical models, MM-310 was associated with fewer hematologic toxicities than free docetaxel and was shown to induce tumor regression or controlled tumor growth," said Daryl Drummond, Ph.D., Vice President of Discovery at Merrimack. "We believe these data support clinical evaluation of MM-310 across multiple tumor types."

Methodology and Results:

MM-310 preclinical data include:

Several preclinical models of breast, lung and prostate cancer were used to examine the differences between MM-310 and free docetaxel. In preclinical testing, MM-310 had a significantly longer half-life than free docetaxel, with prolonged exposure at the tumor site.

Treatment with MM-310 at a dose less than one half of the maximum tolerated dose led to full tumor regression for up to 100 days with no evidence of regrowth post-treatment as compared to free docetaxel-treated tumors with a time to progression of approximately 40 days. In chronic tolerability preclinical studies, MM-310 was found to be 4-7 times better tolerated than free docetaxel, with a maximum tolerated dose of at least 120 mg/kg, compared to 20 mg/kg for free docetaxel and no detectable hematological toxicity.

Preclinical data support the hypothesis that encapsulation of a docetaxel prodrug in a stable and long circulating, targeted liposome may protect against docetaxel-induced hematologic toxicity in in vivo models. Preclinical data confirmed that MM-310 administered weekly at 40 mg/kg induced less hematologic toxicity than free docetaxel administered weekly at 10 mg/kg.

In a sampling of approximately 200 tumors, EphA2 was found to be expressed in tumor cells, myofibroblasts and tumor-associated blood vessels. EphA2 overall prevalence was found to range from 50 – 100% across multiple indications. In cell models, a high level of specificity was observed in the MM-310 EphA2-targeted liposome, with a more than 100-fold increase in liposome cell association when compared to non-targeted liposomes. EphA2-targeted liposomes were shown to bind to and penetrate EphA2 positive cells, while non-targeted liposomes showed minimal binding.

On April 21, 2016 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), reported that the FDA Office of Orphan Products Development (OOPD) has granted orphan drug designation for its lead product candidate, VAL-083, in the treatment of ovarian cancer (Press release, DelMar Pharmaceuticals, APR 21, 2016, View Source [SID:1234511212]). The investigational drug candidate previously received an orphan designation for glioma and medulloblastoma in the United States and glioma in Europe.

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VAL-083 is a "first-in-class" small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments.

"We are pleased to receive the designation, which is timely in light of new data presented this week with supporting the potential for VAL-083 in the treatment of ovarian cancer," said Jeffrey Bacha, chairman and CEO of DelMar Pharmaceuticals. "This announcement is representative of the progress we’ve made in developing VAL-083 which we believe positions the therapy as a viable treatment option for ovarian cancer patients."

DelMar’s collaborators from the University of Texas MD Anderson Cancer Center (MD Anderson) presented preclinical data demonstrating that VAL-083 appears to have a distinct mode of action from platinum-based chemotherapies widely used in the treatment of ovarian cancer. In these studies, VAL-083 demonstrated an ability to circumvent cisplatin-resistance in all ovarian cell lines tested.

These new data were presented in a poster entitled, "Enhanced in vitro activity of dianhydrogalactitol (VAL-083) in combination with platinum drugs: Impact of p53 and platinum-resistance," on Monday April 18, 2016 at the annual meeting of the American Association of Cancer Research.

According to Evaluate Pharma, the market for ovarian cancer therapies is expected to be approximately $570 million in 2016 and is projected grow to more than $3.5 billion in 2022. The American Cancer Society estimates that approximately 22,000 women will receive a new diagnosis of ovarian cancer and approximately 14,000 women will die from ovarian cancer in the United States each year. Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system.

Ovarian cancers are commonly treated with a platinum-based chemotherapy regimen. Initial tumor response rates are relatively high; however, up to 75% of ovarian cancer patients who respond to initial treatment will relapse within approximately 18 months after completing first-line therapy. Median survival in platinum-resistant recurrent ovarian cancer patients ranged from six to nine months in published studies.

"Ovarian cancer represents the latest indication where our current research, combined with historical clinical activity demonstrated in NCI-sponsored clinical trials, supports our strategy to focus our development of VAL-083 as a new treatment option for ovarian cancer patients who have failed or are unlikely to respond to modern chemotherapeutic regimens," said Mr. Bacha. "We look forward to working with the FDA’s Office of Orphan Product Development and leading investigators to advance this program alongside our ongoing efforts in glioblastoma and other solid tumors."

On April 21, 2016 Actelion Ltd (SIX: ATLN) reported its results for the first three months of 2016 (Press release, Actelion, APR 21, 2016, View Source [SID:1234511208]).

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OPERATING HIGHLIGHTS

Excellent Opsumit (macitentan) trajectory sustained
Outstanding early US launch momentum for Uptravi (selexipag)
Significant recruitment drive into Phase III programs
3 New compounds delivered from Drug Discovery to the clinic
FINANCIAL HIGHLIGHTS

Product sales of CHF 589 million (+11% at CER)
Opsumit sales grow to CHF 178 million
Uptravi sales of CHF 35 million – enhanced by launch inventory
Core operating income of CHF 249 million (+8% at CER)
2016 financial guidance upgrade: High single-digit percentage core operating income growth, at constant exchange rates and barring unforeseen events
% variance
in CHF millions
(except for per share data) 3M 2016 3M 2015 in CHF at CER(1)
US GAAP results
Net revenue 590 515 14 11
Operating income 208 190 10 3
Net income 178 159 12 5
Diluted EPS 1.64 1.38 19 11
Core performance(2)
Product sales 589 515 14 11
Core operating income 249 218 14 8
Core net income 215 185 16 10
Core diluted EPS 1.98 1.61 23 17
Cash flow 3M 2016 3M 2015
Operating cash flow 172 94
Capital expenditure -5 -6
Free cash flow 67 -57
Net cash position as of 31 March 472 913
CER percentage changes are calculated by reconsolidating both the 3M 2015 and 3M 2016 results at constant currencies (the average monthly exchange rates for 3M 2015).
Actelion continues to measure, report and issue guidance on its core operating performance, which management believes more accurately reflects the underlying business performance. The Group believes that these non-GAAP financial measurements provide useful supplementary information to investors. These non-GAAP measures are reported in addition to, not as a substitute for, US GAAP financial performance.

Jean-Paul Clozel, MD, Chief Executive Officer, commented: "Actelion has started the year very well. Opsumit continues on its exceptional launch trajectory and Uptravi is off to an excellent start – much better than anyone could have expected. Our other products are also performing well, our pipeline projects are advancing and our discovery efforts continue to deliver compounds into the clinic. With the business performing better than anticipated, even while launching new products and investing in future products, I am confident to upgrade our financial guidance."

Otto Schwarz, Chief Operating Officer, commented: "We are very pleased with the Uptravi launch in the United States. After almost three months, approximately 650 patients are on treatment with Uptravi. We assume the majority of patients are now benefitting from an all-oral triple combination therapy. The Opsumit launch momentum continues across all regions and markets. Our outcome-based PAH portfolio now accounts for 40% of our sales, with Tracleer for the first time contributing less than 50% of sales, thus demonstrating the progress in the transformation of our PAH business."

André C. Muller, Chief Financial Officer, commented: "The strong start to 2016, along with some more clarity on a number of factors – including the strong Opsumit and Uptravi launch dynamics and stable pricing in Japan for Opsumit and Tracleer – enables us to increase the outlook for the full year. Barring unforeseen events, we now expect high single-digit percentage core operating income growth, at constant exchange rates."

SALES UPDATE

Actelion delivered an outstanding first quarter driven by the continued successful uptake of Opsumit, a very strong Uptravi launch, consistently strong recruitment of new PAH patients across markets, and ERA market expansion due to increased combination therapy with PDE-5 inhibitors.

In the US, sales increased by 25% at CER, driven by the strong Uptravi launch, continued Opsumit momentum and ERA market share gains. European sales were flat at CER with increased Opsumit uptake and Tracleer use in the digital ulcer indication offset by continued pricing pressure and market erosion from generics. Sales in Japan increased by 11% at CER and were driven by Opsumit (launched in June 2015), Veletri, and Zavesca (Japanese trade name Brazaves). Sales in the rest of the world decreased by 14%, at CER.

Comparing average exchange rates for the first three months of 2016 to the first three months of 2015, the Swiss franc weakened, mostly against the US dollar and the Euro, resulting in a positive currency variance of 17 million Swiss francs.

Sales by product – year-to-date

% variance
in CHF millions 3M 2016 3M 2015 in CHF at CER
Opsumit 178 95 88 82
Tracleer 290 344 -16 -18
Uptravi 35 - - -
Veletri 24 19 24 20
Ventavis 27 31 -15 -18
Valchlor 9 5 88 80
Zavesca 25 20 27 26
Others 2 2 23 30
Total product sales 589 515 14 11
Sales by region – year-to-date

% variance
in CHF millions 3M 2016 3M 2015 in CHF at CER
United States 327 252 30 25
Europe* 164 162 1 0
Japan 50 42 20 11
Rest of the world 49 59 -18 -14
Total product sales 589 515 14 11
*Europe = EU28 and Switzerland

PAH FRANCHISE
Opsumit
Sales of Opsumit (macitentan) amounted to 178 million Swiss francs for the first three months of 2016, an increase of 82% at CER compared to the first three months of 2015. This increase is driven by the continued uptake trajectory with commercial availability in over 30 countries. The strong enrollment continues to be driven by treatment-naïve patients together with increased early combination with PDE-5 inhibitors.

Uptravi
Sales of Uptravi (selexipag) amounted to 35 million Swiss francs since the product was launched in the United States on 4 January 2016. Of this total amount, approximately 20 million Swiss francs can be attributed to the launch inventory as Uptravi is available in 10 different presentations across the various doses. At the end of March, approximately 650 patients were using this outcome-based, oral selective IP receptor agonist, originally discovered by Nippon Shinyaku.

Market authorization has so far been received from the US FDA (21 December 2015) and Health Canada (20 January 2016), New Zealand’s Medsafe (17 March 2016) and Australia’s TGA (18 March 2016). In Europe, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Uptravi for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II-III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as monotherapy in patients who are not candidates for these therapies. A CHMP positive opinion is one of the final steps before marketing authorization is granted by the European Commission. The European Commission is expected to issue a final decision in the coming months.

Submission of the registration dossier to other health authorities is ongoing, with regulatory reviews underway in Japan, South Korea, Switzerland, Taiwan and Turkey.

Tracleer
Sales of Tracleer (bosentan) amounted to 290 million Swiss francs for the first three months of 2016, a decrease of 18% at CER compared to the first three months of 2015. This decrease is mostly a consequence of lower volumes in countries where Opsumit is availabledue to lower enrollments of new patients as well as switches to Opsumit. Underlying units sold globally decreased by 14%. Tracleer sales were further impacted by continued pricing pressure in Europe and increased generic bosentan competition, notably in Spain. Positively, Tracleer sales were supported by the digital ulcer indication in Europe, the DU launch in Japan and continued solid demand in markets where Opsumit is not yet available. In March 2016, Actelion Japan was notified that the biannual Japanese pricing review would lead to no change.

Following the Pediatric Investigation Plan (PIP) compliance statement from the European Committee for Medicinal Products for Human Use (CHMP), applications for extension of the Supplementary Protection Certificate (SPC) were filed in 19 EU countries and have been granted in 15 of those.

Veletri
Sales of Veletri (epoprostenol for injection) amounted to 24 million Swiss francs for the first three months of 2016, an increase of 20% at CER compared to the first three months of 2015. The increase was mostly driven by increased market penetration, successful launches in additional markets, notably in France – the biggest European i.v. epoprostenol market in terms of prostacyclin patients – and continued growth in Japan (where it is marketed as Epoprostenol "ACT"). In March 2016, Actelion Japan was notified of an average 12% price cut for Veletri, effective 1 March 2016. At the end of March 2016, Veletri was available in 15 countries globally.

Ventavis
Sales of Ventavis (iloprost) amounted to 27 million Swiss francs for the three months of 2016, a decrease of 18% at CER compared to the first three months of 2015. The underlying unit decrease of 24% is due to continued competitive pressure.


SPECIALTY PRODUCTS
Valchlor
Sales of Valchlor (mechlorethamine) for the first three months of 2016 amounted to 9 million Swiss francs. In the US, the company is continuing its efforts to establish Valchlor as an option in the treatment algorithm for early-stage mycosis fungoides, a type of Cutaneous T-Cell Lymphoma (MF-CTCL). In France, patients benefited from the drug under a temporary authorization for use ("ATU") program initiated during the second half of 2014. The regulatory dossier is currently under review with the European Medicines Agency (under the trade name Ledaga).

Zavesca
Sales of Zavesca (miglustat) amounted to 25 million Swiss francs for the first three months of 2016, an increase of 26% at CER compared to the first three months of 2015. Underlying units sold increased by 15%. Sales in the US were strong due to a very low prior year base as a consequence of last year’s inventory adjustment. In Europe, sales were lower by 5% mainly due to launch of generic miglustat, which has become commercially available (approved for the type 1 Gaucher disease indication only) in Spain, Sweden and the Czech Republic. Sales in Japan (where it is marketed as Brazaves) were 13% higher driven by increased patient demand in the Niemann-Pick type C indication.

RESULTS DAY CENTER
Investor community: To make your job easier, we provide links to all relevant documentation, such as a full financial review, reconciliation US-GAAP to Core results and geographical breakdown by product, from the Results Day Center on our corporate website: www.actelion.com/results-day-center.


PIPELINE
In the first three months of 2016, the company significantly increased enrollment into both the cadazolid and ponesimod Phase III studies, raising confidence that full recruitment can be achieved by the end of the year.

During the first quarter a new chemical entity entered into man for neurological disorders. Other projects in the clinical development pipeline are progressing according to plan.

Compound Indication Study Status
Registration Selexipag PAH GRIPHON Regulatory reviews ongoing
Phase III Cadazolid Clostridium difficile-associated diarrhea IMPACT Ongoing
Macitentan Eisenmenger syndrome MAESTRO Ongoing
Ponesimod Multiple sclerosis OPTIMUM Ongoing
Phase II Clazosentan Reversal of vasospasm associated with aneurysmal subarachnoid hemorrhage REVERSE Ongoing
Endothelin Receptor Antagonist Specialty cardiovascular disorders - Initiating
Macitentan Chronic thromboembolic pulmonary hypertension MERIT Ongoing
Macitentan Combined pre- and post-capillary pulmonary hypertension MELODY Complete
Ponesimod Graft-versus-host disease - Ongoing
Cenerimod Systemic lupus erythematosus - Ongoing
Phase Ib Lucerastat Fabry disease - Complete
Phase I NCE Neurological disorders - Complete
NCE Neurological disorders - Ongoing
NCE Neurological disorders - Ongoing
NCE Cardiovascular disorders - Ongoing