On April 29, 2016 Novartis reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Afinitor (everolimus) tablets for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin in adults with progressive disease (Press release, Novartis, APR 29, 2016, View Source [SID:1234511628]). Schedule your 30 min Free 1stOncology Demo! If approved by the European Commission (EC), Afinitor would address an unmet need as there are currently few or no treatment options in Europe for patients with these diseases.
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"This important milestone reinforces our long-standing commitment to the NET community by providing solutions to help improve outcomes for patients with these rare and difficult-to-treat cancers," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs.
Neuroendocrine tumors are a type of cancer that originate in neuroendocrine cells throughout the body, and most commonly arise in the GI tract, lungs or pancreas[1],[4]. NET can be defined as functional or nonfunctional[5]. The majority of patients with NET (72%) have nonfunctional NET, which are characterized by symptoms caused by tumor growth, such as intestinal obstruction, pain and bleeding for GI NET, and asthma, chronic obstructive pulmonary disease and pneumonia for lung NET[5],[6],[7],[8]. In contrast, functional NET are characterized by symptoms caused by the oversecretion of hormones and other substances[5]. Five to 44% (depending on site of tumor origin) of those with GI NET and 28% of those with lung NET have advanced disease at time of diagnosis, meaning the cancer has spread to other areas of the body and patients face limited treatment options[1],[4]. Progression, or the continued growth or spread of the tumor, is typically associated with poor prognoses[9].
The positive CHMP opinion was based on efficacy and safety data from a pivotal Phase III study (RADIANT-4) showing everolimus reduced the risk of progression in patients with progressive, well-differentiated, nonfunctional, locally advanced or metastatic NET of GI or lung origin by 52% (hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.35-0.67; p<0.00001) vs placebo. Additionally, the data showed everolimus increased median progression-free survival (PFS) by 7.1 months: median PFS by central review was 11.0 months (95% CI, 9.2-13.3) in the everolimus arm and 3.9 months (95% CI, 3.6-7.4) in the placebo arm[3].
In the pivotal trial, the most common treatment-related grade 3/4 adverse events (AEs) (>=5%) for everolimus and placebo, respectively, were stomatitis (9.0% vs 0.0%), diarrhea (7.0% vs 2.0%) and infections (7.0% vs 0.0%)[1]. The most common treatment-related, all-grade AEs (incidence >=10%) were stomatitis (63%), diarrhea (31%), fatigue (31%), infections (29%), rash (27%) and peripheral edema (26%)[3].
The EC typically adheres to the recommendation of the CHMP and delivers its final decision within three months. The decision will be applicable to all 28 European Union member states plus Iceland and Norway.
In February, the US Food and Drug Administration approved Afinitor for the treatment of adult patients with progressive, well-differentiated, nonfunctional NET of GI or lung origin that are unresectable, locally advanced or metastatic. Additional worldwide regulatory filings for this indication are underway.
RADIANT-4 Study Design
RADIANT-4 (RAD001 In Advanced Neuroendocrine Tumors) is a Phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study. It examined the efficacy and safety of everolimus plus best supportive care (BSC) vs placebo plus BSC in 302 patients with unresectable, progressive, well-differentiated, nonfunctional, locally advanced or metastatic NET of GI (excluding pancreatic) or lung origin. The primary endpoint of RADIANT-4 was PFS based on independent radiological assessment evaluated by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included overall survival and best overall response rate (defined as complete response plus partial response)[10].
Patients were randomized 2:1 to receive a daily dose of 10 mg everolimus tablets or matching placebo. During treatment, all patients received BSC, which excluded somatostatin analogues (SSAs). Patients had low or intermediate grade histology, no history or active symptoms of carcinoid syndrome, and documented disease progression within the previous 6 months, and were required to have stopped treatment with SSAs for 4 weeks before study entry[10].
The safety profile of everolimus was consistent with what has been observed in previous oncology studies of this drug[10].
About Afinitor (everolimus) tablets
Afinitor (everolimus) tablets is approved in 99 countries, including the US and in the European Union, for locally advanced, metastatic or unresectable progressive NET of pancreatic origin. Afinitor is not indicated for the treatment of patients with functional carcinoid tumors in the US. Afinitor is now approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic.
It is also approved in more than 120 countries including the US and European Union for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy (in the US, specifically following sunitinib and sorafenib).
Additionally, Afinitor is approved in more than 100 countries including the United States and European Union for advanced HR+/HER2- breast cancer in combination with exemestane, after prior endocrine therapy.
Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names Afinitor or Votubia, Certican and Zortress and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.
Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.
Important Safety Information about Afinitor (everolimus) tablets
Afinitor/Votubia can cause serious side effects including lung or breathing problems, infections (including sepsis), and kidney failure, which can lead to death. Patients taking concomitant angiotensin-converting enzyme (ACE) inhibitors may be at an increased risk for angioedema. Mouth ulcers and mouth sores are common side effects. Afinitor/Votubia can affect blood cell counts, kidney and liver function, and blood sugar, cholesterol, and triglyceride levels. Afinitor/Votubia may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor/Votubia and for up to eight weeks after ending treatment. Women taking Afinitor/Votubia should not breast feed. Fertility in women and men may be affected by treatment with Afinitor/Votubia.
The most common adverse drug reactions (incidence >=10 percent) are mouth ulcers, skin rash, feeling tired or weak, diarrhea, infections (including upper respiratory tract infection, sore throat and runny nose, sinusitis, middle ear infection and pneumonia), absence of menstrual periods, high levels of cholesterol, nausea, decreased appetite, low level of red blood cells, acne, abnormal taste, irregular menstrual periods, inflammation of lung tissue, swelling of extremities or other parts of the body, high level of blood sugar, itching, weight loss, nose bleeds, cough and headache. The most common grade 3-4 adverse drug reactions (incidence >=2 percent) are mouth ulcers, infections (including pneumonia), low level of red blood cells, absence of menstrual periods, high level of blood sugar, feeling tired or weak, diarrhea, low white blood cells, inflammation of lung tissue and spontaneous bleeding or bruising. Cases of hepatitis B reactivation, blood clots in the lung or legs, and pneumocystis jirovecii pneumonia (PJP) have been reported. Abnormalities were observed in hematology and clinical chemistry laboratory tests.
Author: [email protected]
Janssen’s IMBRUVICA® (ibrutinib) Receives Positive CHMP Opinion for Expanded Use in Previously Untreated Chronic Lymphocytic Leukaemia Patients
On April 29, 2016 Janssen-Cilag International NV reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a Positive Opinion, recommending broadening the existing marketing authorisation for ibrutinib as a single agent for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (Press release, Johnson & Johnson, APR 29, 2016, View Source [SID:1234511627]). Schedule your 30 min Free 1stOncology Demo! Ibrutinib is approved for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL), or adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy, or in first line in the presence of 17p deletion or TP53 mutation (genetic mutations typically associated with poor treatment outcomes) in patients unsuitable for chemo-immunotherapy and in adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.1
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The Positive Opinion of the CHMP was based on data from the Phase 3, randomised, open-label RESONATE-2 (PCYC-1115) clinical trial, as recently published in The New England Journal of Medicine (NEJM).2 Findings showed ibrutinib provided a significant improvement in all efficacy endpoints versus chlorambucil in patients aged 65 or older with newly diagnosed CLL. The progression-free survival (PFS) rate at 18 months was 90 percent for ibrutinib versus 52 percent for chlorambucil.2 Ibrutinib also significantly prolonged overall survival (OS) (HR=0.16 percent CI, 0.05, 0.56; P=0.001), with a 24-month survival rate of 98 percent, compared to 85 percent for patients in the chlorambucil arm.2 The safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies.2 The most common adverse reactions (ARs) (≥20 percent) of any Grade in the RESONATE-2 trial for ibrutinib were diarrhoea (42 percent), fatigue (30 percent), cough (22 percent) and nausea (22 percent).2
CLL is a chronic disease, and the prevalence rate in Europe among men and women is approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively. Median overall survival ranges between 18 months and more than 10 years according to the stage of disease.3
"Janssen is proud to be leading the charge with our ongoing efforts to transform the treatment experience for patients with difficult to treat blood cancers, such as CLL," said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. "Ibrutinib continues to demonstrate impressive clinical results, and the data on which this recommendation is based once again highlight its potential to deliver improved patient outcomes for suitable patients."
This regulatory milestone follows the decision by the U.S. Food and Drug Administration on 04 March 2016, to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.
About Ibrutinib
Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B cells.4 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells. It also slows down the progression of the cancer.1
Ibrutinib is currently approved in Europe for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL); adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy, or in first line patients with CLL in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy; and in adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.5 Regulatory approval for additional uses has not yet been granted. Investigational uses for ibrutinib, alone and in combination with other treatments, are underway in several blood cancers.
Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except in the United States, where Janssen Biotech, Inc. and Pharmacyclics co-market it. Janssen and Pharmacyclics are continuing an extensive clinical development programme for ibrutinib, including Phase 3 study commitments in multiple patient populations – please see the ibrutinib summary of product characteristics for further information.
About RESONATE-2
Findings of the RESONATE-2 (PCYC-1115) trial showed ibrutinib provided a significant improvement in progression-free survival and other key clinical endpoints versus chlorambucil in patients aged 65 or older with newly diagnosed CLL. The progression-free survival (PFS) rate at 18 months was 90 percent for ibrutinib versus 52 percent for chlorambucil.2 Ibrutinib also significantly prolonged overall survival (OS) (HR=0.16 percent CI, 0.05, 0.56; P=0.001), with a 24-month survival rate of 98 percent, compared to 85 percent for patients in the chlorambucil arm.2
The safety of ibrutinib in the previously untreated CLL patient population was consistent with previously reported studies.2,5 The adverse reactions (AR) reported in the RESONATE-2 trial reflect exposure to ibrutinib with a median duration of 17.4 months versus a median exposure to chlorambucil of 7.1 months: nearly 2.5 times longer exposure for ibrutinib.2 The most common non-haematological ARs of Grade ≥3 were pneumonia, hypertension and diarrhoea (all 4 percent).2
About CLL
In most patients, CLL is generally a slow-growing blood cancer of the white blood cells called B-lymphocytes.6 The median age at diagnosis is 72 years,7 and incidence rates among men and women in Europe are approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively.8 CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years according to the stage of disease.3 The disease eventually progresses in the majority of patients, and patients are faced with fewer treatment options each time. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.
Sanofi Comments on Medivation’s Rejection of Proposal
On April 29, 2016 Sanofi reported that they have commented on Medivation, Inc.’s (NASDAQ: MDVN) rejection of Sanofi’s non-binding all-cash proposal to acquire Medivation for $52.50 per share (Press release, Sanofi, APR 29, 2016, View Source [SID:1234511597]). Schedule your 30 min Free 1stOncology Demo! Combining Sanofi and Medivation represents a compelling strategic and financial opportunity to drive immediate and certain value for Medivation’s shareholders while benefiting patients and both companies’ respective stakeholders. Sanofi’s all-cash proposal represents over a 50 percent premium to Medivation’s two-month volume weighted average trading price (VWAP) prior to takeover rumors.
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Sanofi is a disciplined acquirer and has a strong acquisition track-record. While to date Medivation has chosen not to enter into discussions regarding this value-creating transaction, Sanofi remains committed to the combination and looks forward to engaging directly with Medivation shareholders with regard to our proposal.
Medical Need part of Immedica Group and Laboratoires CTRS in Nordic collaboration
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.
6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]
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.