Healthy organic growth across the board, North American Products business continues strong growth (Press release, Fresenius, JUL 31, 2018, View Source [SID1234528443])

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Underlying Care Coordination margin improved

Results continue to be impacted by strong currency headwinds

Calcimimetics continue to evolve

Divestiture of Sound Inpatient Physicians successfully closed

NxStage acquisition expected to close in the second half of 2018

Rice Powell, Chief Executive Officer of Fresenius Medical Care, stated: "In the second quarter, we have seen solid growth resulting in a strong net income increase of 22 percent at constant currency – excluding the positive impact of the successful and efficient closing of the Sound Inpatient Physicians divestment. On the back of the strong development of our Products business and continued growth of our Services business, we expect growth to further accelerate in the second half of 2018."

Strong Products growth
Revenue in the second quarter of 2018 was again significantly impacted by foreign currency effects, resulting in a 2% increase at constant currency to EUR 4,214 million (-6% at current rates). Adjusting the second quarter of 2017 for the impact from the IFRS 15 implementation, revenue in the second quarter of 2018 was up by 5% at constant currency. Health Care Services revenue increased by 1% at constant currency to EUR 3,385 million, driven by growth in same market treatments and contributions from acquisitions, partially offset by the effects from the implementation of IFRS 15. Excluding the negative effects from the implementation of IFRS 15 Health Care Service revenue increased by 4% at constant currency. Health Care Products revenue grew by 6% at constant currency to EUR 829 million. The increase was driven by higher sales of hemodialysis products and renal pharmaceuticals. Organic growth for Health Care Services was 3% and for Health Care Products 6%. Dialysis treatments increased by 3%, mainly as a result of growth in same-market treatments.

In the first half of 2018, revenue was stable at constant currency with EUR 8,189 million (-9% at current rates). Excluding the effect from the implementation of IFRS 15 revenue was up by 3% at constant currency. Health Care Services revenue decreased by 1% at constant currency (-11% at current rates) based on a strong comparable first half of 2017 and unfavourably affected by the implementation of IFRS 15 and the VA Agreement. Health Care Products revenue increased by 6% at constant currency (flat at current rates).

Significant contribution from divestitures of Care Coordination activities
Total operating income (EBIT) reached EUR 1,401 million, an increase of 162% at constant currency (+140% at current rates) in the second quarter of 2018. The strongest contributor was the gain related to the divestitures of Care Coordination activities. The significant contribution of EUR 833 million also includes the positive effect of gains from currency translation adjustments. Adjusting for the gain as well as the prior year impact from the VA Agreement, EBIT grew by 2% at constant currency (-4% at current rates) with an EBIT margin of 13.5%.

In the first half of 2018, EBIT increased by 68% at constant currency to EUR 1,898 million (+54% at current rates). Adjusted for the effects described above, EBIT increased by 3% at constant currency (-6% at current rates) and the EBIT margin was 13.2%.

Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA was exceptionally strong in the second quarter of 2018 with EUR 994 million (+270% at current rates), mainly driven by the gain related to the divestitures of Care Coordination activities. Excluding the gain related to the divestitures of Care Coordination activities, the increase in net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA was 22% at constant currency (+15% at current rates). Further adjusting for the prior year impact from the VA Agreement and the positive effect from the U.S. Tax Reform, net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA grew by 6% on a constant currency basis to EUR 273 million (flat at current rates). Based on the number of approximately 306.4 million shares (weighted average number of shares outstanding), basic earnings per share (EPS) amounted to EUR 3.24 (+270% at current rates). On a comparable basis the company generated an EPS of EUR 1.00, up by 22% at constant currency and 15% at current rates. On an adjusted basis EPS increased by 6% to EUR 0.89 at constant currency (flat at current rates).

For the first half of 2018, net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA increased by 141% at constant currency (+121% at current rates) to EUR 1,273 million, mainly driven by the gain related to the divestitures of Care Coordination activities. Adjusted for this effect, net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA reached EUR 599 million, an increase of 13% at constant currency (+4% at current rates). Further adjusting for the prior year impact from the VA Agreement and the positive effect from the U.S. Tax Reform, net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA reached EUR 517 million in the first half of 2018, an increase of 7% at constant currency (-1% at current rates).

Organic growth across all Reporting Segments
North America revenue, which represents 71% of total revenue in the second quarter of 2018, was stable at constant currency and reached EUR 2,971 million (-8% at current rates). Excluding the effect from the implementation of IFRS 15 revenue was up by 4% at constant currency. Organic growth was 3%.

Dialysis Care revenue increased by 4% to EUR 2,232 million at constant currency (-4% at current rates). The growth at constant currency was mainly driven by an increase in organic revenue per treatment, same market treatment growth and contributions from acquisitions, to some extent diluted by the implementation of IFRS 15 and the VA Agreement in the prior year. Adjusted for the implementation of IFRS 15, Dialysis Care revenue increased by 7% at constant currency. Organic revenue per treatment increased by 4%, same-market treatments grew by 2% and acquisitions contributed 1%. At constant currency, Care Coordination revenue decreased by 18% (-24% at current rates), driven by the shift of calcimimetic drugs into the clinical environment and the implementation of IFRS 15, partially offset by improved performance in certain services prior to divestiture. Excluding the effect from the implementation of IFRS 15 Care Coordination revenue decreased by 10% at constant currency.

In the U.S., the average revenue per treatment, adjusted for the implementation of IFRS 15 and excluding the 2017 impact of the VA Agreement, increased by USD 13 from USD 341 to USD 354. The increase was mainly driven by the introduction of calcimimetic drugs in the clinical environment, which is still evolving. The increase was partially offset by lower revenue from commercial payors, as expected, and higher implicit price concessions (IFRS 15).

Cost per treatment in the U.S., adjusted for the implementation of IFRS 15, increased by USD 14 from USD 272 to USD 286. This development was largely a result of the introduction of calcimimetic drugs in the clinical environment as well as increased property and other occupancy related costs, partially offset by lower costs for health care supplies.
At constant currency, Health Care Products revenue showed a strong increase of 10% to EUR 210 million due to higher sales of renal pharmaceuticals, machines and hemodialysis concentrates. Lower external sales in peritoneal dialysis products affected the overall positive development.

Total operating income for the North America segment was EUR 1,286 million in the second quarter of 2018, an increase of 200% at constant currency (+174% at current rates). This increase was mainly driven by the gain related to divestitures of Care Coordination activities. Adjusted for this impact and the 2017 effects from the VA Agreement, operating income (EBIT) was EUR 453 million compared to EUR 471 million in the second quarter of 2017. The adjusted operating income margin was stable at 15.2%.

For the first half of 2018, North America revenue decreased by 3% at constant currency to EUR 5,746 million (-13% at current rates). Adjusted for the implementation of IFRS 15 (EUR 270 million), revenue increased by 1% at constant currency (-9% at current rates). Mainly driven by the gain related to divestitures of Care Coordination activities operating income went up by 83% at constant currency (+66% at current rates) to EUR 1,648 million in the first half of 2018.

As of the end of June 2018, the company was treating 199,527 patients (+3%) at its 2,439 clinics (+4%) in North America. Dialysis treatments increased by 3%.

EMEA revenue increased by 5% at constant currency (+2% at current rates) to EUR 652 million in the second quarter of 2018, mainly driven by the positive development in Health Care Services revenue and Health Care Products revenue, which increased by 5% and 4%, respectively, at constant currency. The increase in Health Care Services revenue was driven by same-market treatment growth and acquisitions. Dialysis Products revenue grew by 5% at constant currency (+2% at current rates) to EUR 319 million, due to higher sales of dialyzers, machines, bloodlines, products for acute care treatments and renal pharmaceuticals.

Non-dialysis Products revenue decreased by 8% at constant currency (-8 % at current rates) to EUR 18 million, primarily due to slightly lower sales volumes.

Operating income was EUR 105 million in the second quarter of 2018. The operating income margin decreased from 17.6% to 16.1%, mainly due to unfavorable impacts from lower income from equity method investees, higher personnel costs in certain countries and an increase in bad debt expenses.

For the first half of 2018, EMEA revenue increased by 5% at constant currency to EUR 1,288 million (+3% at current rates), while operating income of EUR 214 million was 5% below last year´s level at constant currency (-6% at current rates).

As of the end of June 2018, the company had 63,589 patients (+4%) being treated at 758 clinics (+4%) in the EMEA region. Dialysis treatments increased by 4%.

Asia-Pacific revenue grew by 7% at constant currency to EUR 422 million (+1% at current rates) in the second quarter of 2018. Health Care Services revenue in the region increased by 7% at constant currency to EUR 191 million (flat at current rates). Care Coordination activities contributed EUR 49 million (+32% at constant currency, +24% at current rates) to Health Care Services revenue. This strong Care Coordination growth in Asia Pacific was mainly related to acquisitions and a strong organic revenue growth. Health Care Products showed again a solid business performance, growing 6% at constant currency to revenues of EUR 231 million (+2% at current rates). This growth was mainly driven by higher sales of hemodialysis products, partially offset by lower sales of products for acute care treatments. Operating income reached the same level as the previous year’s quarter (EUR 78 million). The operating income margin decreased slightly to 18.4%, driven by unfavorable foreign currency impacts and increased costs for the business growth, mainly in China.

For the first half of 2018, Asia-Pacific revenue increased by 10% at constant currency to EUR 814 million. Operating income decreased by 1% at constant currency with EUR 152 million (-5% at current rates).

As of the end of June 2018, the company had 30,578 patients (+2%) being treated at 385 clinics in Asia-Pacific. Dialysis treatments increased by 2%.

Latin America delivered revenue of EUR 164 million in the second quarter of 2018, an improvement of 11% at constant currency (-10% at current rates). This growth was mainly driven by a strong growth in Health Care Services (+15% at constant currency) due to an increase in organic revenue per treatment, acquisitions and growth in same market treatments. Health Care Products revenue in Latin America increased by 2% at constant currency to EUR 46 million, due to higher sales of machines and peritoneal dialysis products and negatively affected by lower sales of dialyzers. With an operating income of EUR 11 million the segment generated an operating income on previous year’s level. The operating income margin remained at 6.8%.

For the first half of 2018, Latin America revenue increased by 14% at constant currency to EUR 334 million (-7% at current rates). Operating income was EUR 25 million, an increase of 5% at constant currency (-6% at current rates).

As of the end of June 2018, the company was treating 31,494 patients (+4%) at 233 clinics in Latin America (+1%). Dialysis treatments increased by 4%.

Net interest expense was EUR 84 million compared to EUR 95 million in the second quarter of 2017, a decrease of 6% at constant currency (-11% at current rates). The decrease was driven by a replacement of high interest-bearing senior notes by debt instruments at lower rates as well as a decreased debt level. Income tax expense was EUR 262 million for the second quarter of 2018, which translates into an effective tax rate of 19.9%, compared to last year’s Q2 with a tax rate of 30.8%. The strong reduction was largely driven by the U.S. Tax Reform and the gain related to divestitures of Care Coordination activities.

Strong cash flow generation
In the second quarter of 2018, the company generated EUR 656 million of operating cash flow, compared to EUR 883 million provided by operating activities in last year’s second quarter. This decrease was mainly driven by increased accounts receivable related to the addition of calcimimetics into the Medicare ESRD payment bundle and unfavorable foreign currency effects. The number of days sales outstanding (DSOs) decreased sequentially by three days compared with Q1 2018 to reach 82 days. Free cash flow (Net cash used in operating activities, after capital expenditures, before acquisitions and investments) amounted to EUR 429 million for the three months ended June 30, 2018 compared to EUR 690 million for the same period of 2017. Free cash flow in percent of revenue was 10.2% and 15.4% for the three months ended June 2018 and 2017, respectively.

Sound Physicians divestiture successfully closed
On June 28, Fresenius Medical Care announced the closing of the divestiture of Sound Inpatient Physicians Holdings, LLC to an investment consortium led by Summit Partners. In the second half of 2017, the Sound Physicians business generated revenue of EUR 559 million and a net income of EUR 38 million. The 2017 basis has been adjusted accordingly for measuring the performance against the 2018 outlook.

Closing of NxStage Medical acquisition expected for second half 2018
In August 2017, Fresenius Medical Care signed an agreement with NxStage Medical, a U.S.-based medical technology and services company, to acquire all outstanding shares of NxStage Medical through a merger. The merger, which has been approved by NxStage’s board, NxStage stockholders and authorities in Germany, is still subject to regulatory approval by the Federal Trade Commission under the Hart-Scott-Rodino Act. Fresenius Medical Care has exercised its contractual right under the merger agreement to extend the original closing deadline by 90 days from August 7, 2018 to November 5, 2018. Fresenius Medical Care expects to close the transaction in 2018.

Employees
As of June 30, 2018, Fresenius Medical Care had 111,263 employees (full-time equivalents) worldwide, compared to 112,163 employees at the end of June 2017. This decrease was mainly attributable to divestitures of certain Care Coordination activities.

Outlook 2018
The company expects revenue1 growth between 5% and 7% at constant currency. Net income on a comparable basis2 is expected to increase by 13% to 15% at constant currency and on an adjusted basis2,3 to increase by 7% to 9% at constant currency.

The targets exclude the effect from the planned acquisition of NxStage Medical and the gain (loss) related to divestitures of Care Coordination activities.

1 2017 adjusted for the effect of IFRS 15 implementation and the contribution of Sound Physicians in H2 2017
2 Attributable to shareholders of Fresenius Medical Care AG & Co. KGaA, adjusted for the contribution from Sound Physicians in H2 2017
3 VA Agreement, Natural Disaster Costs, FCPA related charge, U.S. Tax Reform

Conference call
Fresenius Medical Care will host a conference call to discuss the results of the second quarter today at 3:30 p.m. CEDT / 9:30 a.m. EDT. Details will be available on the company’s website www.freseniusmedicalcare.com in the "Investors/Events" section. A replay will be available shortly after the call.

On July 31, 2018 Synthetic Biologics, Inc. (NYSE American: SYN), a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients, reported that the Company intends to release its operational highlights and financial results for the quarter ended June 30, 2018 on Wednesday, August 8, 2018, and to host a conference call the same day at 4:30 p.m. EDT (Press release, Synthetic Biologics, JUL 31, 2018, View Source [SID1234528020]). The dial-in information for the call is as follows:

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U.S. (toll free): 1-888-347-5280
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Participants are asked to dial in 15 minutes before the start of the call to register. The call will also be webcast over the Internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source An archived replay of the call will be available for approximately ninety (90) days at the same URL, View Source beginning approximately one hour after the call’s conclusion.

On July 30, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Glycotope GmbH (hereafter, Glycotope) reported that have entered into an exclusive worldwide licensing agreement to develop an antibody drug conjugate (ADC) by combining Daiichi Sankyo’s proprietary ADC technology with Glycotope’s investigational tumor-associated TA-MUC1 antibody gatipotuzumab (formerly PankoMab-GEX), building on a previous 2017 option agreement (Press release, Daiichi Sankyo, JUL 30, 2018, https://www.glycotope.com/daiichi-sankyo-enters-worldwide-licensing-agreement-with-glycotope-for-gatipotuzumab-antibody-drug-conjugate/ [SID1234537463]).

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Under the terms of the licensing agreement, Daiichi Sankyo has worldwide exclusive rights to develop and commercialize gatipotuzumab as an ADC. Glycotope will receive an upfront payment and is eligible for clinical, regulatory and sales milestone payments, as well as royalties on net sales worldwide from Daiichi Sankyo. Specific financial terms have not been disclosed.

"With the licensing of gatipotuzumab with the intention of developing an ADC, we now have seven novel ADCs in development, which demonstrate our commitment to maximizing the potential of our proprietary ADC payload and linker technology to help address the unmet needs of patients with cancer worldwide," said Tom Held, Vice President, Head, Antibody Drug Conjugate Task Force, Oncology Research and Development, Daiichi Sankyo. "We are excited by the rapid progress we have made in our collaboration with Glycotope and look forward to the continued clinical development of this potentially first-in-class TA-MUC1-targeting ADC."

"This agreement with Daiichi Sankyo highlights the potential and wide applicability of gatipotuzumab," said Henner Kollenberg, Managing Director of Glycotope. "Our world-leading glyco-biology expertise has allowed us to create a novel anti-TA-MUC1 monoclonal antibody with carbohydrate mediated tumor-specificity and high affinity binding. We look forward to continuing to work with Daiichi Sankyo on this ADC program and on the further development of gatipotuzumab in other formats."

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Daiichi Sankyo’s proprietary ADC technology is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered. Gatipotuzumab is an investigational monoclonal antibody that enables tumor-specific binding to a novel carbohydrate-induced conformational epitope, TA-MUC1, which is extensively expressed in many tumor types including ovarian, lung and breast.1

On July 30, 2018 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that the U.S. Food and Drug Administration (FDA) has allowed the Company’s IND application for its ADXS-HOT drug candidate for non-small cell lung cancer (NSCLC) (Press release, Advaxis, JUL 30, 2018, View Source [SID1234527954]). Advaxis anticipates that because of this timely allowance, the first patient in the Phase 1/2 trial for this NSCLC drug candidate will be dosed by the end of 2018.

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ADXS-HOT is a cancer-type specific immunotherapy approach that leverages the Company’s proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary tumor-associated antigens. To date, more than 10 drug candidates have been designed for different tumor types in the ADXS-HOT program.

"This is an exciting time for Advaxis as we prepare to initiate the first clinical trial with a drug candidate from our ADXS-HOT program. This drug candidate, ADXS-503, has been designed for the treatment of patients with NSCLC," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "With our increased strategic focus on neoantigen-based therapeutics, including the personalized, patient-specific approach of our ADXS-NEO program, already in a clinical trial, we anticipate having five neoantigen-based drug candidates in clinical evaluation by the end of 2019. Our next two ADXS-HOT drug candidates will focus on prostate and bladder cancers. These two tumor types, along with NSCLC, were prioritized based on our evaluation of a number of factors relating to each, including the unmet medical need, time and investment required to demonstrate meaningful clinical activity and immunological sensitivity," concluded Mr. Berlin.

The Company plans to initiate a Phase 1/2 clinical trial that will seek to establish the safety, tolerability and effectiveness of ADXS-503 administered alone and in combination with a checkpoint inhibitor in approximately 50 patients with metastatic NSCLC in different lines of therapy, at up to 20 centers across the U.S.

"I am pleased we can move forward to advance our first trial with ADXS-503, the first drug candidate in our ADXS-HOT program. This is an important clinical milestone as we seek to demonstrate proof-of-concept for ADXS-HOT immunotherapy in NSCLC, where there remains significant unmet need despite the introduction of checkpoint inhibitors and targeted therapies," said Andres Gutierrez, M.D., Ph.D., Chief Medical Officer and Executive Vice President of Advaxis. "Earlier drug candidates from our Lm platform expressing a single antigen have shown a favorable safety profile and preliminary clinical activity in more than 500 subjects treated to date across different tumor types. This clinical experience with prior Lm drug candidates, combined with our ability to leverage the large capacity of our Lm vector to express multiple neoantigens and other tumor-associated antigens, provides the foundation for our belief that ADXS-HOT drug candidates such as ADXS-503 for NSCLC can provide a new standard for off- the-shelf neoantigen vaccines."

Advaxis affirms plans to submit a total of four INDs for drug candidates from its ADXS-HOT program by the fourth quarter of 2019. Beyond NSCLC, prostate cancer and bladder cancer, the fourth ADXS-HOT drug candidate will be selected from breast, colorectal, ovarian or head and neck cancers.

About ADXS-HOT

ADXS-HOT is a program that leverages the Company’s proprietary Lm technology to target hotspot mutations that commonly occur in specific cancer types. ADXS-HOT drug candidates are designed to target acquired shared or "public" mutations in tumor driver genes along with other cancer-testes and oncofetal tumor-associated antigens that also commonly occur in specific cancer types. Although ADXS-HOT drug candidates have not yet been tested in patients, they are an off-the-shelf treatment approach been designed to potentially treat all patients with a specific cancer type, without the need for pretreatment biomarker testing, biopsy, DNA sequencing or diagnostic testing.

About ADXS-NEO

ADXS-NEO is an investigational personalized Lm-based immunotherapy designed to generate immune response against mutation-derived tumor-specific neoantigens identified through DNA sequencing of a patient’s own tumors. The program focuses on creating a customized treatment for each patient targeting multiple neoantigens found in a biopsy of the patient’s tumor. ADXS- NEO is being developed in partnership with Amgen.

On July 30, 2018 Astex Pharmaceuticals, a member of the Otsuka group of companies, and Otsuka Pharmaceutical Co. Ltd., reported that top-line results from the ASTRAL-1 study evaluating the efficacy and safety of guadecitabine (SGI-110) in adults with previously untreated AML who are not eligible for intensive induction chemotherapy (Press release, Astex Pharmaceuticals, JUL 30, 2018, View Source [SID1234527955]). The study did not meet its co-primary endpoints: complete response (CR) rate (p>0.04), and overall survival (OS) (p>0.01) as per the protocol analysis plan, compared with the control arm of physician’s choice of azacitidine, decitabine, or low dose cytarabine. Evaluation of the study’s secondary endpoints and safety data is ongoing. The full data will be presented at an upcoming scientific meeting.

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The company continues to focus on completing the ongoing global phase 3 ASTRAL-2 and ASTRAL-3 studies evaluating guadecitabine in the treatment of relapsed and refractory AML and relapsed and refractory MDS and CMML.

"We are disappointed in the outcome of the ASTRAL-1 study," said Mohammad Azab, Astex’s president and chief medical officer. "The study used very strict criteria of ineligibility to receive intensive chemotherapy based on age (over 75 years) or poor performance status (ECOG PS of 2 or 3) or comorbidities, which made it a difficult population to show superior benefit of guadecitabine." Dr. Azab also added, "ASTRAL-1 is the largest global prospective study ever conducted in this specific patient population with low intensity therapy, with 815 patients randomized, of whom about 90% were treated with hypomethylating agents or HMAs (guadecitabine, azacitidine, or decitabine). The large body of clinical and genetic data will still provide the medical community with very valuable insights into the role of several prognostic clinical and genetic markers that may influence outcome with HMA treatment. We are extremely grateful to all the patients, physicians and other healthcare professionals, and partner research and manufacturing organizations who contributed to this global effort. We are now looking forward to the completion of the ASTRAL-2 and ASTRAL-3 studies currently actively recruiting in two different indications."

About Guadecitabine (formerly SGI-110)

Guadecitabine is a next-generation DNA hypomethylating agent.1,2 Guadecitabine was rationally designed to be resistant to degradation by cytidine deaminase, prolonging the exposure of tumor cells to the active metabolite, decitabine, thus ensuring greater uptake of decitabine into the DNA of rapidly dividing cancer cells.3 Guadecitabine, through the action of decitabine, inhibits DNA methyl transferase (DNMT), with the potential to reverse aberrant DNA methylation, an epigenetic change characteristic of many cancer cells that results in silencing of critical genes. This action may restore the expression of silenced tumor suppressor genes and tumor-associated antigens.4 Through this re-expression of silenced genes, guadecitabine may have the potential to sensitize tumor cells to other anticancer agents,5,6,7 including immunotherapeutics,8 as well as re-sensitizing cancer cells previously resistant to chemotherapeutics.7

Guadecitabine is currently being studied in two additional phase 3 studies:

ASTRAL-2: A randomized, open-label study in leukemia patients with relapsed or refractory acute myeloid leukemia (AML) following intensive chemotherapy. See www.clinicaltrials.gov NCT02920008.
ASTRAL-3: A randomized, open-label study in myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) after failure of treatment with azacitidine, decitabine, or both. See www.clinicaltrials.gov NCT02907359.
In addition, guadecitabine is being evaluated in over twenty investigator and company-sponsored trials in other hematological malignancies and in solid tumors, both as a single agent, and in combination with chemotherapy or immunotherapy.

Guadecitabine was designed to be administered subcutaneously as a low-volume, stable formulation.

About the ASTRAL-1 Study

The ASTRAL-1 study evaluated the efficacy and safety of guadecitabine (formerly SGI-110) in adults with previously untreated AML who are not eligible for intensive induction chemotherapy (see www.clinicaltrials.gov NCT02348489). The study is the largest global prospective study ever conducted in this specific patient population, with 815 patients randomized from 163 investigator sites in 24 countries worldwide. The study compared guadecitabine, delivered subcutaneously (SC) 60mg/m2/day for 5 days, with physicians’ choice of azacitidine IV or SC 75 mg/m2/day for 7 days, decitabine IV 20 mg/m2/day for 5 days, or low dose cytarabine SC 20 mg bid for 10 days, all administered in 28-day cycles. In addition to the co-primary endpoints of OS and CR, the study evaluated multiple secondary endpoints including progression-free survival; composite CR or CRc (CR + CRi + CRp); overnight stays in hospital; red cell / platelet transfusions; QOL (EQ-5D-5L); duration of response and safety.

About Acute Myeloid Leukemia

AML is the most common form of acute leukemia in adults.9 There were an estimated 21,380 new cases of AML diagnosed in the US in 2017,10 and an estimate of 10,590 patients were projected to have died from AML in the US in 2017.11 Although 60 to 80 percent of AML patients less than 60 years of age may achieve a complete response (CR) with standard intensive induction chemotherapy,12 the outlook for patients 60 years of age or more is significantly worse, with response rates less than 50 percent, cure rates following transplant remaining at less than 10 percent and a median survival of less than one year.12,13,14 These figures have not significantly improved during the last three decades. These patients have few therapeutic options available.15,16 Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients where comorbidities and other consequences of aging may often render them ineligible to receive intensive induction chemotherapy, thus denying them a potentially curative transplant.14