On April 28, 2016 Medical Need part of Immedica Group reported that it has entered into an exclusive supply and distribution agreement with the French company Laboratoires CTRS, regarding marketing and sale of CTRS portfolio of pharmaceuticals in the Nordic region (Press release, Immedica Pharma, APR 28, 2016, View Source [SID1234555256]). In 2013, CTRS received EU marketing authorization and orphan drug market exclusivity for its product Orphacol (cholic acid), indicated for the treatment of two rare inborn errors of metabolism in the primary bile acid synthesis: 3β-hydroxy-Δ5-C27-steroid oxidoreductase and Δ4-3-oxosteroid-5β-reductase deficiency. A few weeks ago, the European commission approved a centralized marketing authorization for the company’s second product, Neofordex, containing a high and appropriate dosage (40 mg) of dexamethasone, a common component used in combination with other pharmaceuticals in the treatment of multiple myeloma. While already well established in the treatment protocols, prior to the approval of Neofordex, dexamethasone has only been available in low strengths (0.5-4 mg), forcing patients to take a very high number of tablets (10-80 per day) to achieve an appropriate dosage. In addition to the increased convenience for the patients, since an adequate dose exposure is critical for efficacy of the treatment regimen, the expectation is that the availability of a tablet in appropriate strength could improve compliance and thereby potentially the treatment outcome. Under the agreement, Medical Need gains the rights to Neofordex and Orphacol in Denmark, Finland, Iceland, Norway and Sweden, and will be responsible for the distribution, marketing and sale of the products in that territory. "CTRS has a very exciting portfolio which fits well with our competencies and capabilities in Medical Need", said Tomas Gloveus, Head of Marketing and Sales at Medical Need, and continued, "Orphacol and Neofordex both fulfil high unmet medical needs, which have previously not been adequately served in this region, and we look forward to now being able to make these products available to the affected patients in the Nordic countries."
About Multiple Myeloma and Neofordex

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Multiple myeloma (MM) is a form of cancer that affects a type of white blood cells called plasma cells. Plasma cells are part of the immune system and normally helps the body fight infections by producing antibodies. Rather than producing helpful antibodies, in MM, the cancer cells produce abnormal proteins that over time damages the kidneys. MM also causes cancer cells to accumulate in the bone marrow, where they crowd out healthy blood forming cells which results in a deficiency of red and white blood cells, as well as blood platelets. This in turn leads to a number of different symptoms, depending on the deficient cell; anemia (paleness, fatigue), leukopenia (sensitivity to infection) and thrombocyotopenia (bleeding and bruising). MM also causes damage to the bone and skeleton. MM is slightly more prevalent in men and typically affects the elderly (>65), but may affect individuals as young as 30. MM is treated by a number of treatment protocols, which typically involve several different pharmaceuticals. Over the past years, several new products have been approved for the treatment of MM as part of such treatment protocols. A common component in most of the treatment protocols is dexamethasone (denoted as "d" or "D" in the protocol abbreviations), a potent and long-acting corticosteroid, which has been shown to play an important part in the efficacy of the different regimens. The typical daily dose of dexamethasone in the treatment of MM is 40 mg. Neofordex is the only approved pharmaceutical which contains 40 mg of dexamethasone in a single tablet. Prior to the approval of Neofordex, dexamethasone has only been available in low strengths (0.5-4 mg), forcing patients to take a very high number of tablets (10-80 per day) to achieve an appropriate dosage. An adequate dose exposure of dexamethasone has been shown to be of high importance for the efficacy of the treatment regimen (Kobayashi et al., Int J Hematol. 2010 Nov;92(4):579-86). It is the expectation that the availability of a tablet in an appropriate strength, in addition to the improved convenience from reducing the pill burden for the patients, could translate into increased compliance and thereby potentially improving the treatment outcome. Neofordex was on 2016-03-16 granted a centralized marketing authorization by the European Commission, valid for all markets of the EU, Norway and Iceland. Prior to the regulatory approval, the product has been used extensively on a named patient basis in France, under what is called an ATU cohort, including most French MM patients. The product is planned to be launched in the Nordic and Baltic markets during Q2 2016.

About Inborn Errors of Primary Bile Acid Synthesis and Orphacol
Inborn errors of primary bile acid synthesis are very rare inherited conditions, caused by mutations in the genes encoding certain enzymes responsible for the liver’s production of bile acids, one of the key components of the bile. Left untreated, these enzyme deficiencies lead to the accumulation of hepatotoxic metabolites and progression to irreversible cholestasis and liver failure, and are usually fatal. Orphacol is the only approved treatment for two particular inborn errors in the primary bile acid synthesis: 3β-hydroxy-Δ5-C27-steroid oxidoreductase and Δ4-3-oxosteroid-5β-reductase deficiency. Orphacol contains cholic acid, which acts through a dual mechanism, by suppressing the faulty bile acid synthesis thus reducing formation of hepatotoxic metabolites and by restoring the biliary secretion and elimination of toxic metabolites through the bile. It also corrects the intestinal malabsorption of fats and fat-soluble vitamins, thereby improving the child’s growth. Treating affected patients with Orphacol can avoid the need for a liver transplantation, an operation with very serious potential consequences, especially in young children. Orphacol was granted a centralized marketing authorization by the European Commission, valid for all markets of the EU, Norway and Iceland in 2013. The product also enjoys orphan drug market exclusivity for 10 years following marketing authorization. The product will immediately be made available on the Nordic and Baltic markets.

On April 27, 2016 QIAGEN N.V. (NASDAQ: QGEN; Frankfurt Prime Standard: QIA) reported results of operations for the first quarter of 2016, delivering on goals for adjusted net sales and adjusted earnings per share results while reaffirming full-year 2016 targets and announcing plans for a new $100 million share repurchase program (Filing, Q1, QIAGEN, 2016, APR 28, 2016, View Source [SID:1234511598]).

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"QIAGEN achieved goals for the first quarter of 2016 while moving ahead on initiatives to accelerate growth and drive further innovation in our Sample to Insight portfolio, which enables customers to gain valuable molecular insights from any biological sample. We are on track to deliver the benefits of these efforts, which include accelerating our performance during the course of 2016 and making targeted investments to enhance our mid- to long-term growth prospects," said Peer M. Schatz, Chief Executive Officer of QIAGEN N.V.

"All regions contributed to QIAGEN’s performance in the first quarter of 2016, fueled by strong single-digit CER growth in Molecular Diagnostics when excluding the expected headwind in U.S. HPV test sales, and better trends among Pharma customers. Our growth drivers grew at a double-digit CER pace and reached 35% of total sales, with the blockbuster QuantiFERON latent TB test providing about 10% of sales and accelerating to above a 25% CER annual growth pace. QIAsymphony automation solutions delivered solid growth in system placements and double-digit CER growth in consumables. We are excited about the early successes of the GeneReader NGS System launch, which surpassed our goal for placements in the first quarter of 2016 amid very positive customer feedback about the benefits of this first truly complete Sample to Insight solution for next-generation sequencing. QIAGEN remains on track to achieve our 2016 goals for higher adjusted net sales and earnings, and for accelerating growth in the coming years."

First quarter 2016 results

Change
In $ millions, except per share information
Q1 2016
Q1 2015
$
CER
Net sales, adjusted
298.4
298.7
0%
+2%
Operating income, adjusted
53.4
67.4
-21%
Net income, adjusted
44.0
51.5
-15%
Diluted EPS, adjusted
$0.19
$0.22
Diluted EPS CER, adjusted
$0.19
$0.22

For information on adjusted figures, please refer to the reconciliation table accompanying this release. Adjusted net sales is a non-GAAP measure that includes all revenue contributions from bioinformatics acquisitions.

Adjusted net sales grew 2% at constant exchange rates (CER) in the first quarter of 2016 compared to the same period in 2015, but were unchanged at actual rates due to two percentage points of adverse currency movements. All regions as well as the Pharma, Molecular Diagnostics and Academia customer classes were higher on growth in consumables and related revenues (+2% CER / 88% of sales) and instruments (+6% CER / 12% of sales). About one percentage point of total CER growth came from the late 2015 acquisition of MO BIO Laboratories Inc., a leader in sample technologies for metagenomics and microbiome analysis, while the rest of the portfolio added about one percentage point. Excluding the expected impact of lower U.S. HPV test sales, which created two percentage points of headwind, adjusted net sales rose 4% CER.

Operating income declined to $15.4 million in the first quarter of 2016 from $35.1 million in 2015. Adjusted operating income, which excludes items such as business integration, acquisition-related costs and the amortization of intangible assets acquired in business combinations, declined 21% to $53.4 million from $67.4 million in the first quarter of 2016. The adjusted operating income margin was 18% of net sales in the first quarter of 2016 compared to 23% in the same period of 2015. The adjusted gross margin declined to 70% of sales from 73% in the year-ago period, impacted by lower gross margins for companion diagnostic partnerships and costs to relocate manufacturing for some products to the operational headquarters site in Hilden, Germany. Sales & Marketing expenses were higher as a percentage of sales to support commercialization of the growth drivers and geographic expansion. Research & Development costs rose slightly as a percentage of sales, and General & Administrative expenses fell as a percentage of sales from the first quarter of 2015.

Net income attributable to owners of QIAGEN N.V. was $14.9 million in the first quarter of 2016, or $0.06 per diluted share (based on 236.9 million diluted shares), compared to $19.5 million, or $0.08 per share (based on 237.4 million diluted shares) in the 2015 quarter. Adjusted net income was down 15% to $44.0 million, or $0.19 per share ($0.19 CER) from $51.5 million, or $0.22 per share.

At March 31, 2016, cash and cash equivalents rose to $355.8 million from $290.0 million at December 31, 2015. Net cash provided by operating activities was $48.7 million in the first quarter of 2016, down from $62.8 million in the year-ago period. Net cash provided by investing activities was $17.7 million compared to $26.8 million. Net cash used in financing activities was $4.0 million compared to $182.3 million in the first quarter of 2015, which included $187.8 million for debt repayment. Free cash flow declined to $30.3 million from $39.7 million.

"We are determined to deliver on the targets set for 2016 while making investments to enhance our mid-term performance, improve profitability and increase cash flows," said Roland Sackers, Chief Financial Officer of QIAGEN N.V. "Our top priority remains to create value, and to do so through disciplined capital allocation. This involves targeted acquisitions such as MO BIO and Enzymatics that complement our Sample to Insight portfolio, as well as share repurchase programs, including our newly announced fourth $100 million program."

Customer class review
An overview of adjusted net sales for the first quarter of 2016, with the MO BIO (December 2015) acquisition contributing to underlying performance in all customer classes for 2016:

Q1 2016
Customer classes
CER change
% of sales
Molecular Diagnostics
+2%
~48%
U.S. HPV sales
-40%
~3%
MDx excluding U.S. HPV sales
+6%
~45%
Applied Testing
-5%
~8%
Pharma
+7%
~21%
Academia
+2%
~23%
Growth rates at constant exchange rates (CER) and sales contributions at actual rates.
Molecular Diagnostics delivered 6% CER growth excluding the expected decline in U.S. HPV test sales, as instrument sales grew at a robust double-digit CER rate, and were complemented by solid single-digit CER gains in consumables and related revenues. Fueled by recent commercial initiatives in the U.S. and Europe, the QuantiFERON-TB test grew over 25% CER and represented about 10% of total QIAGEN sales. Placements of the QIAsymphony automation system under multi-year reagent rental agreements increased as well, with more than one-third of the placements as complete QIAsymphony RGQ systems. Sales of QIAsymphony consumables also rose at a double-digit CER pace, but other consumables sold to this customer group grew more modestly. Personalized Healthcare sales grew at a single-digit CER rate, and included higher revenues from companion diagnostic co-development projects. Global sales of HPV tests fell 26% (6% of total sales) in the first quarter of 2016, as U.S. sales were down 40% (3% of total sales) and sales elsewhere fell at a single-digit CER rate (3% of sales).
Applied Testing faced a tough comparison in the first quarter of 2016 on a combination of steady CER sales of consumables and an approximately 20% CER decline in instrument sales compared to a strong performance in 2015. The Asia-Pacific / Japan region provided growth contributions against declining sales in the Americas and the EMEA regions. QIAGEN expects improving growth trends to emerge in this customer class during 2016.
Pharma advanced at a robust single-digit CER pace for the first quarter of 2016, led by a solid expansion in instrument sales at a double-digit CER pace complemented by mid-single-digit CER growth in consumables and related revenues. All geographic regions contributed to growth over the first quarter of 2015, with the strongest incremental contributions from the EMEA region.
Academia generated growth in the Americas and Asia-Pacific regions compared to the first quarter of 2015, while the EMEA region declined at a single-digit CER rate. Sales of instruments as well as consumables and related revenues grew at modest single-digit CER rates in the first quarter of 2016. Funding trends are expected to improve during the course of 2016 in the U.S. and Europe given recent government decisions to increase spending for life sciences research.

Geographic review

Q1 2016
Region
CER change
% of sales
Americas
+1%
46%
Europe / Middle East / Africa
+7%
34%
Asia-Pacific / Japan
+4%
20%
Growth rates at constant exchange rates (CER) and sales contributions at actual rates.
The EMEA region led the performance with single-digit CER gains in the United Kingdom, France and Germany along with double-digit CER growth in Turkey. The Americas rose 5% CER excluding U.S. HPV test sales, supported by single-digit CER growth in Latin America. Asia-Pacific / Japan benefited from double-digit CER growth in South Korea, China and Australia, while Japan fell at a significant double-digit CER rate. Sales in the top seven emerging markets (Brazil, Russia, India, China, South Korea, Mexico and Turkey) rose 19% CER and provided 13% of sales.
On course to accelerate growth and further innovation

QIAGEN continues to build momentum for its Sample to Insight portfolio, with the growth drivers providing double-digit CER growth and more than one-third of total sales. Among the recent developments:
Commercialization of the GeneReader NGS System, the world’s first complete Sample to Insight solution designed for any laboratory to deliver actionable results from next-generation sequencing, showed strong momentum, as broad demand drove initial placements in the first quarter of 2016. GeneReader is gaining recognition as a highly efficient, user-friendly solution to address fragmented NGS workflows and bottlenecks that have hindered labs from gaining actionable insights from sequencing applications. The novel Price Per Insight (PPI) model provides a cost-effective and reliable way for labs to gain access to this technology. The GeneReader NGS System also has been recognized with a 2016 Red Dot design award.

QuantiFERON-TB Gold (QFT), the modern standard for detecting latent tuberculosis (TB) infection and the top-selling interferon-gamma release assay (IGRA) worldwide, was chosen in two recent national screening guideline processes. South Korea and Taiwan selected QFT for screening at-risk individuals as part of national TB control efforts. Also, the U.S. Preventive Services Task Force (USPSTF) released draft guidelines that would expand screening to patients in primary care settings. The positive draft "B" rating recommended use of the modern and more accurate IGRAs, and also the tuberculin skin test.

QIAGEN’s industry-leading portfolio of liquid biopsy solutions, which use fluids such as blood to detect and profile diseases, continue to gain visibility. Among many recent studies using QIAGEN kits, a report in JAMA Oncology showed the use of QIAamp cell-free DNA extraction kits to achieve promising data for detection of mutations in non-small cell lung cancer (NSCLC).

A new companion diagnostic collaboration was launched in April with Mirati Therapeutics, Inc. to co-develop and commercialize a test to guide the use of a novel compound currently in development for NSCLC patients with cancer-driving alterations of the MET gene. This is the initial project in a new master collaboration agreement with Mirati.

A wide-ranging collaboration with 10x Genomics was announced at the annual Advances in Genome Biology and Technology (AGBT) conference in February. The two companies will combine products to co-develop and co-market NGS and single-cell biology analysis workflows and informatics solutions. These new products will be essential in addressing challenges such as how to analyze long-read sequence data for insights into complex diseases.

More than 170 new QIAseq Targeted RNA Panels were launched during the first quarter of 2016 for gene expression profiling and efficient RNA sequencing with any NGS sequencer. These panels employ a novel proprietary technology to enable highly quantitative output not possible with other NGS approaches and to allow researchers to analyze interactions among genes, cellular phenotypes and disease processes. Data analysis and insights are integrated into the QIAseq panels with comprehensive QIAGEN bioinformatics solutions.

QIAGEN introduced the RNA-seq Explorer Solution, integrating bioinformatics with advanced sample technologies to generate clear insights from liquid biopsies such as exosomes for cancer research. RNA-seq Explorer integrates Ingenuity Pathway Analysis and Biomedical Genomics Workbench together into one solution for the analysis and interpretation of "omics" data to make sense of inherently noisy data from sequencing body fluids.

A conditional voluntary takeover offer was submitted in March to purchase all shares of Exiqon A/S of Denmark, a leader in the emerging market for non-coding RNA (ncRNA) such as microRNA (miRNA) and long non-coding RNA (lncRNA). Exiqon’s portfolio is highly synergistic with several areas of QIAGEN’s portfolio and adds a set of proprietary technologies and know-how, including Locked Nucleic Acid (LNA) technology that improves specificity and sensitivity in PCR, NGS target enrichment and functional assays. The acquisition of Exiqon, which had sales of about $20 million in 2015, is expected to be completed in mid-2016 for about $100 million.

New $100 million plan marks fourth QIAGEN share repurchase program
QIAGEN announced today the launch of its fourth $100 million share repurchase program. This comes after expiry of the third program, under which approximately 3.0 million shares were repurchased on the Frankfurt Stock Exchange at a volume-weighted average price of EUR 19.33 per share for EUR 57 million (approximately $70 million). Details of the fourth repurchase program will be made public in line with Article 4, Section (2) of EC regulation 2273/2003 (so-called Safe Harbor). Repurchased shares are held in treasury to satisfy obligations for exchangeable debt instruments and employee share-based remuneration plans. Further information is available on the QIAGEN website (www.qiagen.com).

2016 outlook
QIAGEN reaffirms its full-year 2016 expectations (announced in January 2016) for adjusted net sales to rise approximately 6% CER from the current portfolio. This includes about one percentage point of growth from the late 2015 acquisition of MO BIO, and approximately one percentage point of headwind from reduced U.S. HPV test sales. Adjusted diluted earnings per share (EPS) at CER are expected to rise approximately in line with sales for the full year to approximately $1.10-1.11 CER. Based on exchange rates as of April 1, 2016, currency movements against the U.S. dollar are expected to have an adverse impact on results at actual rates of approximately two percentage points on full-year 2016 adjusted net sales, and about $0.02 per share on adjusted diluted EPS. These full-year 2016 expectations do not take into account the publicly announced tender offer to acquire the Danish biotechnology company Exiqon A/S (announced in March 2016) or any further acquisitions that could be completed during the year.

For the second quarter of 2016, adjusted net sales are expected to rise approximately 4% CER, which includes approximately two percentage points of headwind from reduced U.S. HPV test sales, and for adjusted EPS of approximately $0.22 CER. Based on exchange rates as of April 1, 2016, QIAGEN expects currency movements to have an adverse impact on results for the second quarter at actual rates of approximately two percentage points on adjusted net sales and about $0.01 per share on adjusted diluted EPS.

Use of adjusted results
QIAGEN reports adjusted results, as well as results on a constant exchange rate (CER) basis, and other non-U.S. GAAP figures (generally accepted accounting principles), to provide additional insight into its performance. These results include adjusted net sales (includes all revenue contributions from bioinformatics acquisitions), adjusted gross profit, adjusted operating income, adjusted net income attributable to owners of QIAGEN N.V., adjusted diluted EPS and free cash flow. Adjusted results are non-GAAP financial measures that QIAGEN believes should be considered in addition to reported results prepared in accordance with GAAP, but should not be considered as a substitute. Free cash flow is calculated by deducting capital expenditures for Property, Plant & Equipment from cash flow from operating activities. QIAGEN believes certain items should be excluded from adjusted results when they are outside of its ongoing core operations, vary significantly from period to period, or affect the comparability of results with its competitors and its own prior periods. Reconciliations are included in the tables accompanying this report.

On April 28, 2016 Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of cortisol, reported data supporting the clinical advancement of its proprietary, selective cortisol modulator, CORT125134 (Press release, Corcept Therapeutics, APR 28, 2016, http://www.corcept.com/news_events/view/pr_1461877347 [SID:1234511592]). The company has begun recruiting patients for a Phase 1/2 trial of the compound to treat patients with solid-tumor cancers. It also expects to begin recruiting patients for a Phase 2 study of CORT125134 to treat patients with Cushing’s syndrome this quarter.

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"Advancing CORT125134 is an important step in protecting and extending our growing Cushing’s syndrome franchise and in developing cortisol modulation for a wide range of other serious diseases," said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. "This selective cortisol modulator has shown great promise. We are optimistic that, for some patients with Cushing’s syndrome, CORT125134 may be even better than our approved product, Korlym – just as effective, but without the side effects associated with Korlym’s affinity for the progesterone receptor. Equally important, we look forward to investigating its potential as a treatment for solid-tumor cancers."

CORT125134 is the lead compound in Corcept’s proprietary portfolio of selective cortisol modulators. It is a non-steroidal competitive antagonist of the glucocorticoid receptor (GR) that does not bind to the body’s other hormone receptors, including the progesterone receptor (PR). Korlym’s interaction with PR results in termination of pregnancy and can cause endometrial thickening and irregular vaginal bleeding in some women. CORT125134 is proprietary to Corcept and is protected by composition of matter and method of use patents extending to 2033.

Advancement to Phase 2 Trials Supported by Positive Pre-Clinical and Phase 1 Data

"The data generated so far make this compound a promising candidate to treat both Cushing’s syndrome and, potentially, a number of solid-tumor cancers," said Hazel Hunt, Ph.D., Corcept’s Vice President of Research. "Its Phase 1 data showed that it shares Korlym’s potent affinity for GR, one of the receptors to which cortisol binds. Our clinical testing showed that it can prevent the effects of the steroid prednisone, a commonly-used synthetic GR agonist. Preventing the effects of prednisone is a very important finding, as it mirrors the essential quality of an effective medical treatment for patients with Cushing’s syndrome."

Corcept’s Phase 1 trial of CORT125134 enrolled 124 healthy volunteers. GR antagonism was tested by measuring CORT125134’s ability to modulate prednisone’s effects on serum osteocalcin, white blood cell counts, glucose metabolism and expression of the FKBP5 gene – a marker of GR activation. With respect to all parameters, CORT125134 was as potent a modulator of prednisone’s activity as Korlym (see Figure 1; p value < 0.0003).

Pharmacokinetic data indicate that CORT125134 is suitable for once-daily dosing.

"Positive Phase 1 data, together with encouraging pre-clinical results, prompted us to advance CORT125134 as a treatment for Cushing’s syndrome as well as a treatment for cancer," continued Dr. Hunt. "Substantial pre-clinical and clinical research suggests that cortisol modulation increases the effectiveness of chemotherapy in some solid-tumor cancers. Pre-clinical data suggest that CORT125134 may be even more potent than Korlym in treating some tumor types."

Corcept and investigators at the University of Chicago have studied the effectiveness of CORT125134 in transgenic mouse models of triple-negative breast cancer (TNBC) and castration-resistant prostate cancer. Mice implanted with TNBC tumor cells were treated with a combination of paclitaxel and CORT125134. Mifepristone (the active ingredient in Korlym) in combination with paclitaxel served as a positive control. As expected, the combination of mifepristone and paclitaxel significantly slowed tumor progression. However, the combination of CORT125134 and paclitaxel slowed it even more (see Figure 2; p value = 0.0004). In a similar experiment, castrated mice seeded with prostate cancer tumor cells were treated with either mifepristone or CORT125134. The outcome was comparable to the TNBC study: When combined with castration (which in humans would be achieved pharmacologically by the administration of an androgen receptor antagonist such as enzalutamide), mifepristone retarded tumor progression, but CORT125134 had an even more pronounced effect (see Figure 3; p value = 0.037).

CORT125134 may also enhance the efficacy of immune-modulation therapy. In an animal model of colon cancer, the addition of CORT125134 to PD-1 monotherapy significantly slowed tumor progression (see Figure 4; p value = 0.013):

Oncology Trial Design

This trial’s initial phase will investigate nab-paclitaxel in combination with CORT125134 to treat any solid-tumor cancer susceptible to treatment with nab-paclitaxel. ("Nab-paclitaxel" is the generic name for Celgene’s drug, Abraxane.) Once a maximum tolerated dose is identified, Corcept plans to open one or more expansion cohorts, each containing 20 patients, to test the combination’s efficacy in one or more of the solid-tumor cancers studied in the dose-finding phase. Possible target indications include TNBC, castration-resistant prostate cancer, ovarian cancer, pancreatic cancer and sarcoma. Other dose-finding cohorts may be enrolled to study CORT125134 in combination with different companion therapeutic agents, including PD-1 inhibitors.

The trial is open-label and will be conducted at sites in the United States, the first of which is open and has begun screening patients.

"That we are advancing the same selective cortisol modulator as a treatment for both a metabolic disease and one or more oncologic indications is a testament to the broad therapeutic potential of cortisol modulation," said Robert S. Fishman, MD, Corcept’s Chief Medical Officer. "We are excited to start these trials."

Cushing’s Syndrome Trial Design

This Phase 2 trial of CORT125134 will enroll 30 patients with endogenous Cushing’s syndrome. Patients will be assigned to a low- or high-dose group and will receive CORT125134 for 12 weeks, with up-titration possible in each group at weeks four and eight. The trial will be open label. Study centers will be located in both the European Union and the United States.

About Korlym

Korlym modulates the effect of cortisol at GR, one of the two receptors to which cortisol binds, thereby inhibiting the effects of excess cortisol in patients with Cushing’s syndrome. Since 2012, Corcept has made Korlym available as a once-daily oral treatment of hyperglycemia secondary to endogenous Cushing’s syndrome in adult patients with glucose intolerance or diabetes mellitus type 2 who have failed surgery or are not candidates for surgery. Korlym was the first FDA-approved treatment for that illness and the FDA has designated it as an Orphan Drug for that indication.

About Cushing’s Syndrome

Endogenous Cushing’s syndrome is caused by prolonged exposure of the body’s tissues to high levels of the hormone cortisol and is generated by tumors that produce cortisol or ACTH. Cushing’s syndrome is an orphan indication that most commonly affects adults aged 20-50. An estimated 10-15 of every one million people are newly diagnosed with this syndrome each year, resulting in over 3,000 new patients annually in the United States. An estimated 20,000 patients in the United States have Cushing’s syndrome. Symptoms vary, but most people have one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing’s syndrome can affect every organ system in the body and can be lethal if not treated effectively.

About Triple-Negative Breast Cancer

Triple-negative breast cancer is a form of the disease in which the three receptors that fuel most breast cancer growth – estrogen, progesterone and the HER-2/neu gene – are not present. Because the tumor cells lack the necessary receptors, treatments that target estrogen, progesterone and HER-2 receptors are ineffective. In 2013, approximately 40,000 women were diagnosed with TNBC. It is estimated that more than 75 percent of these women’s tumor cells expressed the GR receptor to which cortisol binds. There is no FDA-approved treatment and neither a targeted treatment nor an approved standard chemotherapy regimen for relapsed TNBC patients exists.

On April 28, 2016 Acorda Therapeutics, Inc. (Nasdaq:ACOR) reported a financial and pipeline update for the first quarter ended March 31, 2016 (Press release, Acorda Therapeutics, APR 28, 2016, View Source [SID:1234511591]).

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AMPYRA (dalfampridine) 1Q 2016 net revenue was $109.6 Million, a 19% increase over 1Q 2015 net revenue of $92.4 Million. In January 2016, the Company announced an agreement to acquire Biotie, and has received more than 90% of Biotie’s outstanding shares in the tender offer. The Company expects to complete the purchase of 100% of Biotie’s shares in the second half of this year.

"We are well into our transition from a single-product company to a well-diversified biopharmaceutical enterprise, focused on developing therapies to benefit patients with neurological conditions across multiple disease states, including multiple sclerosis, Parkinson’s disease, stroke, migraine and epilepsy," said Ron Cohen, M.D., Acorda’s President and CEO. "Through our business development activities and advancement of our clinical pipeline, we now have four promising Phase 3 assets and, pending successful trial results, have the potential to file for approval of three of these by the end of 2018."

Financial Results

The Company reported a GAAP net loss of $0.5 million for the quarter ended March 31, 2016, or $0.01 per diluted share. The GAAP net loss in the same quarter of 2015 was $3.1 million, or $0.07 per diluted share.

Non-GAAP net income for the quarter ended March 31, 2016 was $3.1 million, or $0.07 per diluted share. Non-GAAP net income in the same quarter of 2015 was $6.5 million, or $0.15 per diluted share. Non-GAAP net income excludes share based compensation charges, non-cash interest charges on our convertible debt, changes in the fair value of acquired contingent consideration, acquisition related expenses, unrealized foreign currency transaction gains, and non-cash tax benefits. A reconciliation of the GAAP financial results to non-GAAP financial results is included with the attached financial statements.

AMPYRA (dalfampridine) Extended Release Tablets, 10 mg – For the quarter ended March 31, 2016, the Company reported AMPYRA net revenue of $109.6 million, up 19% compared to $92.4 million for the same quarter in 2015.

ZANAFLEX CAPSULES (tizanidine hydrochloride), ZANAFLEX (tizanidine hydrochloride) tablets and authorized generic capsules – For the quarter ended March 31, 2016, the Company reported combined net revenue and royalties from ZANAFLEX and tizanidine of $1.2 million compared to $2.6 million for the same quarter in 2015.

FAMPYRA (prolonged-release fampridine tablets) – For the quarter ended March 31, 2016, the Company reported FAMPYRA royalties from sales outside of the U.S. of $2.5 million, compared to $2.3 million for the same quarter in 2015.

Research and development (R&D) expenses for the quarter ended March 31, 2016 were $44.6 million, including $2.1 million of share-based compensation, compared to $30.6 million, including $1.8 million of share-based compensation, for the same quarter in 2015.

Selling, general and administrative (SG&A) expenses for the quarter ended March 31, 2016 were $51.8 million, including $6.0 million of share-based compensation, compared to $48.8 million including $5.3 million of share-based compensation for the same quarter in 2015.

Acquisition related expenses for the Biotie transaction incurred in the quarter ended March 31, 2016 were $7.2 million.

Benefit from income taxes for the quarter ended March 31, 2016 was $9.7 million, including $0.2 million of cash taxes, compared to $2.0 million, including $0.7 million of cash taxes for the same quarter in 2015.

At March 31, 2016, prior to the closing of the Biotie acquisition, the Company had cash, cash equivalents and investments of $431.4 million, up from $353.3 million at December 31, 2015. In January 2016, the Company completed a $75.0 million private placement of its common stock.

First Quarter 2016 Highlights

AMPYRA (dalfampridine)

– AMPYRA revenues for the first quarter of 2016 were $109.6 million, up 19% from the first quarter in 2015. This represents the 12th consecutive quarter of double digit, year-over-year growth for AMPYRA, which was launched in 2010.

– In March, a Markman hearing was held in the U.S. District Court for the District of Delaware related to the consolidated lawsuits that the Company filed against companies that submitted Abbreviated New Drug Applications to the FDA seeking marketing approval for AMPYRA. Also in March, the United States Patent and Trademark Office (USPTO) Patent Trials and Appeal Board (PTAB) instituted the inter partes review (IPR) of four AMPYRA patents. Rulings on the IPR petitions are expected within one year. The Company will continue to defend its intellectual property vigorously.
Dalfampridine in Post-Stroke Walking Difficulty

– In March, the Company completed Phase 1 single-dose pharmacokinetic (PK) studies for three separate once-daily (QD) formulations of dalfampridine. Results for at least one of these formulations met the Company’s criteria. The multi-dose phase of PK testing will begin in the second quarter of 2016.

– Given the progress in its development of a QD formulation of dalfampridine, the Company has made the decision to stop enrollment and conduct an unblinded analysis of the Phase 3 twice-daily (BID) clinical trial data, having reached 50% of its target enrollment in the study, or 270 subjects. As previously stated, unblinding the study ahead of the originally contemplated interim futility analysis was an option. Data are expected by the fourth quarter of 2016 and will be used to inform the design of planned Phase 3 trials in post-stroke.
CVT-301 in Parkinson’s Disease

– In April, data from the CVT-301 Phase 2b clinical trial were one of six platform presentations highlighted during the Movement Disorders Invited Science Session at the 68th Annual Meeting of the American Academy of Neurology.
CVT-427 in Migraine

– In March, the Company announced it had successfully completed a Phase 1 safety/tolerability and pharmacokinetic study for CVT-427. Based on the positive results, the Company is designing protocols for the next phase of development.
Corporate

– In January, the Company announced it had entered into an agreement to acquire Biotie Therapies Corp. The acquisition includes global rights to two clinical-stage compounds in development for treatment of Parkinson’s disease, as well as other assets.

– In April, more than 90% of the outstanding shares of Biotie were tendered to the Company in a tender offer conducted pursuant to the acquisition agreement, meeting the minimum condition to closing the tender offer. The Company expects to complete the acquisition of 100% of Biotie in the second half of 2016.

– In January, the Company completed a $75 million private placement of its common stock and signed a Commitment Letter with JP Morgan for an asset-based credit facility of up to $60 million, which is expected to close in the second quarter of 2016.
The Company will host a conference call today at 8:30 a.m. ET to review its first quarter 2016 results.

To participate in the conference call, please dial (855) 542-4209 (domestic) or (412) 455-6054 (international) and reference the access code 81540360. The presentation will be available via a live webcast on the Investors section of www.acorda.com. Please log in approximately 5 minutes before the scheduled time of the presentation to ensure a timely connection.

A replay of the call will be available from 11:30 a.m. ET on April 28, 2016 until 11:59 p.m. ET on May 5, 2016. To access the replay, please dial (855) 859-2056 (domestic) or (404) 537-3406 (international) and reference the access code 81540360. The archived webcast will be available in the Investor Relations section of the Acorda website at www.acorda.com.