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