Population Pharmacokinetic/Pharmacodynamic Modeling of Sunitinib by Dosing Schedule in Patients with Advanced Renal Cell Carcinoma or Gastrointestinal Stromal Tumor.

Sunitinib is a multi-targeted tyrosine kinase inhibitor used in the treatment of advanced renal cell carcinoma (RCC) and imatinib-resistant/intolerant gastrointestinal stromal tumors (GIST).
A meta-analysis of 10 prospective clinical studies in advanced RCC and GIST was performed to support the development of pharmacokinetic (PK) and PK/pharmacodynamic (PD) models that account for the effects of important covariates. These models were used to make predictions with respect to the PK, safety, and efficacy of sunitinib when administered on the traditional 4-weeks-on/2-weeks-off schedule (Schedule 4/2) versus an alternative schedule of 2 weeks on/1 week off (Schedule 2/1).
The covariates found to have a significant effect on one or more of the PK or PD parameter studies included, age, sex, body weight, race, baseline Eastern Cooperative Oncology Group performance status, tumor type, and dosing schedule. The models predicted that, in both RCC and GIST patients, Schedule 2/1 would have comparable efficacy to Schedule 4/2, despite some differences in PK profiles. The models also predicted that, in both indications, sunitinib-related thrombocytopenia would be less severe when sunitinib was administered on Schedule 2/1 dosing compared with Schedule 4/2.
These findings support the use of sunitinib on Schedule 2/1 as a potential alternative to Schedule 4/2 because it allows for the management of toxicity without loss of efficacy.

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Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies.

Busulfan (Bu)-containing regimens are commonly used in myeloablative regimens prior to allogeneic hematopoietic cell transplantation (HCT). Yet, there is considerable variability on how Bu is administered related to frequency (four times a day, Q6 or daily, Q24) and the combination with other chemotherapeutic agents (cyclophosphamide, Cy or fludarabine, Flu). A prospective cohort study of recipients of Bu-based conditioning according to contemporary practices was used to compare different approaches in using Bu (BuCy Q6 N=495; BuFlu Q24 N=331; BuCy Q24 N=96; BuFlu Q6 N=91) in patients with myeloid malignancies from 2009 to 2011. BuFlu Q24 recipients were more likely to be older and tended to have worse performance status and higher comorbid burden. The cumulative incidence of hepatic veno-occlusive disease (p=0.4), idiopathic pneumonia (p=0.5) and seizures (p=0.5) did not differ across groups. One-year HCT related mortality ranged from 12% to 16% (P=0.8), three-year relapse incidences ranged from 32% to 36% (p=0.8) and three-year overall survival ranged from 51% to 58% (p=0.2) across groups. This study demonstrates that the use of intravenous Bu Q6 or Q24 or accompanied by Cy or Flu have similar outcomes in the myeloablative setting for treatment of myeloid malignancies.
Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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Oxford BioMedica Presents Ground-Breaking Evidence of Long-Term Duration of Therapeutic Expression in Patients from its Proprietary LentiVector® Gene Delivery Platform

On May 6, 2016 Oxford BioMedica plc ("Oxford BioMedica" or "the Company") (LSE:OXB), a leading gene and cell therapy company, reported that new data has been presented from two clinical studies indicating ground-breaking long-term four-year sustained and, in one of the studies, dose-dependent gene expression with the Company’s LentiVector delivery platform (Press release, Oxford BioMedica, MAY 6, 2016, View Source [SID:1234512034]).

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On 5 May 2016, Professor Stéphane Palfi presented a poster on OXB-101, a gene therapy product for the treatment of Parkinson’s disease (PD), at the 19th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in Washington DC, USA. In the Phase I/II study 15 advanced PD patients were treated with OXB-101 in three dose cohorts. OXB-101 demonstrated a favourable safety profile and a statistically significant improvement in motor function relative to baseline at six and 12 months post-treatment. The most recent follow-up data, presented this week, shows that the majority of patients continue to experience improvement in motor function relative to baseline over the four years since treatment. The Company has since developed OXB-102, a more potent version of OXB-101, and is planning to start a Phase I/II study in mid-2016. OXB-102 is Oxford BioMedica’s gene therapy product that utilises its proprietary LentiVector delivery platform to transfer three genes for dopamine synthesis in the striatum.

In addition, on 4 May 2016, Dr Andreas Lauer gave an oral presentation on Oxford BioMedica’s LentiVector-based treatment for neovascular age-related macular degeneration (wet AMD), at the Association for Research in Vision and Ophthalmology (ARVO) conference in Seattle, USA. Consistent with results previously announced at the ARVO conference, the new data presented demonstrates that LentiVector gene expression was dose-dependent and continued without significant decline for more than four years.

Commenting on the new emerging data, John Dawson, Chief Executive Officer of Oxford BioMedica, said: "We are very encouraged by the demonstration of long term expression and clinical benefit in patients indicated by the four-year follow-up data from these two clinical studies. We believe this is the first time gene therapy products have been directly measured in the eye and the longevity in both expression and efficacy to date reinforces the benefits of the Company’s pioneering LentiVector gene delivery platform in the treatment of chronic conditions."

– See more at: View Source#sthash.zAnILG7N.dpuf

PharMerica Reports First Quarter 2016 Results

On May 6, 2016 PharMerica Corporation (NYSE:PMC), a national provider of institutional, specialty home infusion, hospital and oncology pharmacy services, reported its financial results for the first quarter ended March 31, 2016 (Press release, PharMerica, MAY 6, 2016, View Source;p=RssLanding&cat=news&id=2166002 [SID:1234512064]).

1Q’16 Results
Comparison to
1Q’15

Comparison to
4Q’15
Revenue $524.5 million Increase of 2.5% Increase of 0.7%
Adjusted EBITDA $30.3 million Decrease of 14.4% Decrease of 12.7%
Adjusted diluted earnings per share
$0.45 Decrease of 21.1% Decrease of 19.6%
Gross profit $82.0 million Decrease of 7.4% Decrease of 5.4%
Selling, general and administrative $57.0 million Decrease of 3.4% Increase of 2.9%
Generic drug dispensing rate
86.6% Increase of 130 basis points Increase of 30 basis points

Greg Weishar, PharMerica Corporation’s Chief Executive Officer, said, "PharMerica’s first quarter 2016 exceeded our expectations. We believe we are well positioned to deliver on our 2016 financial objectives while driving continued growth and shareholder value creation.

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"Prescriptions dispensed in the first quarter of 2016 were 8.6 million as compared to 8.4 million in the fourth quarter of 2015 and 8.2 million in the third quarter of 2015. This quarter represents the second sequential quarterly increase in prescription volume. In addition, we continue to improve the generic drug dispensing rate; this quarter’s rate of 86.6% represents a 130 basis point increase versus the first quarter of 2015. We expect the generic dispensing rate to further improve as brand patent expirations occur throughout this year and beyond.

"Also, we continue to make progress with respect to the diversification program. Specialty home infusion, oncology and hospital pharmacy management revenues grew 47% on a year over year basis. We achieved revenue growth both organically and through acquisitions. Importantly, EBITDA is growing faster than revenues as higher prescription volumes drive operating leverage. We are confident diversified revenues will exceed $700 million in 2017, and the diversification program will meaningfully contribute to the Company’s overall EBITDA growth over the next several years.

Mr. Weishar concluded, "In summary, we are off to a good start in 2016, and we will continue to pursue attractive acquisitions that drive share and scale. We remain optimistic about the Company’s long-term prospects, and we are well positioned to return to strong growth in 2017 and beyond."

Full Year 2016 Financial Guidance

PharMerica reaffirms its full year 2016 guidance metrics:

Revenue in the range of $2.125 billion to $2.150 billion;
Adjusted EBITDA in the range of $130.3 million to $135.3 million; and
Adjusted diluted earnings per share in the range of $1.95 to $2.05.
The Company notes that its 2016 guidance does not include the effect of any future 2016 acquisitions.

First Quarter 2016 Results

The results for the first quarter 2016 are set forth below:

Key Comparisons of First Quarters Ended March 31, 2016 and 2015:
Revenues for the first quarter of 2016 were $524.5 million compared with $511.6 million for the first quarter of 2015, an increase of 2.5%. The increase in revenues of $12.9 million is due to significant organic growth and acquisitions in the Company’s specialty businesses, partially offset by the 2015 initiative to improve the overall quality mix of clients, the 2016 reduction in Medicare Part D reimbursement and 2015 brand to generic conversions.

Gross profit for the first quarter of 2016 was $82.0 million compared with $88.6 million in the first quarter of 2015; a decrease of 7.4%. The decrease in gross profit was driven by higher drug costs under the Cardinal Health prime vendor agreement, changes made in 2015 to improve the overall quality mix of clients and lower Medicare Part D reimbursement.

Selling, general and administrative expenses were $57.0 million or 10.9% of revenues for the three months ended March 31, 2016 compared to $59.0 million or 11.5% of revenues for the three months ended March 31, 2015. The decrease of $2.0 million was due to cost improvements and lower bad debt expense.
Adjusted EBITDA for the first quarter of 2016 was $30.3 million compared with $35.4 million in the first quarter of 2015; a decrease of 14.4%.

Net income for the first quarter of 2016 was $4.1 million, or $0.13 diluted earnings per share, compared to $9.6 million, or $0.31 diluted earnings per share, for the same period in 2015. Adjusted diluted earnings per share was $0.45 in the first quarter of 2016 compared to $0.57 in the first quarter of 2015.

Cash flows provided by operating activities for the first quarter of 2016 were $62.3 million compared with $44.3 million in the first quarter of 2015. The increase in cash from operating activities is due to a decrease in inventory purchases and a higher accounts payable balance due to the timing of the weekly Cardinal Health prime vendor payment. Additionally, in the first quarter of 2015, $48.8 million of AmerisourceBergen drug purchase payments were withheld.

8-K – Current report

On May 5, 2016 AMRI (NASDAQ: AMRI) reported that it has signed a definitive agreement to acquire all outstanding shares of Prime European Therapeuticals S.p.A., also known as "Euticals", in a transaction valued at approximately $358 million (EUR 315 million), consisting of shares of AMRI common stock, cash, and a seller note (Filing, 8-K, Albany Molecular Research, MAY 6, 2016, View Source [SID:1234512067]).

Euticals is a privately-held company headquartered in Lodi, Italy, specializing in custom synthesis and the manufacture of active pharmaceutical ingredients (APIs). It operates a network of API facilities primarily in Italy, Germany, U.S. and France.

"The acquisition of Euticals will provide us an established custom synthesis presence in Europe and will further build on our expertise in complex APIs, positioning AMRI as a preeminent provider of contract research, development and manufacturing services to the pharmaceutical industry," said William S. Marth, AMRI’s president and chief executive officer.

"Euticals’ expertise with niche and high barrier to entry technologies and products, including certain tetracyclines, monobactams, sterile and fermented APIs and controlled substances, will be a tremendous asset to us. Additionally, Euticals’ large base of over 400 customers will provide us with a number of new large pharma, biotech and generics partners, further extending our global reach and diversifying our revenue.

"Importantly, I am pleased that in connection with the closing of the transaction, Fernando Napolitano will be joining our Board of Directors on behalf of Lauro Cinquantesette, S.p.A (Lauro 57) and its majority investors, Clessidra Capital Partners II and Mandarin Capital Partner SCA SICAR. Clessidra’s and Mandarin’s combined expertise, deep contacts within the European pharmaceutical community and continued guidance will be invaluable to our efforts going forward. Margalit Fine, Euticals’ chief executive officer and former head of European API at Teva, will be leading Euticals’ operations as a senior executive for the combined company," Mr. Marth said.

"On behalf of Lauro 57 and its investors, we couldn’t be more pleased to be joining AMRI," said Clessidra Chief Executive Officer, Maurizio Bottinelli. "Its expertise in developing and manufacturing complex pharmaceutical products is well known and we look forward to joining forces to further expand our presence in the European community."

Strategic Benefits of the Transaction

· Significantly expands AMRI’s capabilities in custom and complex APIs

o Provides AMRI with an established European custom synthesis presence
o Expands expertise in multiple areas: sterile API, steroids, generics, fermentation, controlled substances and monobactams
o Provides an API portfolio that includes 50 active US Drug Master Files (DMFs), 17 EU Certificates of Suitability (COS) or Compliance with the European Pharmacopeia (CEP), 13 Japanese DMFs and 6 South Korean DMFs; with several APIs having filings in more than one of these areas and over two dozen other international filings

· Provides AMRI with global scale and a diverse customer and revenue base

o Euticals brings over 400 customers with no customer concentration
o With 75% of revenue outside North America, Euticals opens up many new markets for AMRI; more than half AMRI’s combined proforma revenue is expected to be ex U.S.
o Euticals brings additional portfolio diversification in generics; AMRI to leverage U.S. base to include Euticals’ strong generic portfolio

Euticals operates a highly regarded API, custom synthesis and fine chemical development and manufacturing business with 2015 revenue and EBITDA of approximately $245 million and $27 million respectively. On a stand-alone basis, Euticals’ full year 2016 revenue is forecast to be between $245 million and $255 million, with adjusted EBITDA1 of between $34 million and $38 million, implying a purchase price multiple, prior to anticipated synergies, of approximately 9.9 times 2016 adjusted EBITDA at the midpoint of the range and excluding deal related costs or purchase accounting impacts. The transaction is expected to be accretive to AMRI’s 2016 non-GAAP diluted earnings per share. AMRI expects to generate operational synergies of $13 to $15 million over the next three years. On a pro forma basis including synergies, AMRI’s full year 2017 revenue is forecast to exceed $750 million, with adjusted EBITDA margins of approximately 20%.

Transaction Details, Financing and Closing

AMRI expects to finance the transaction through the issuance of approximately 7 million shares of AMRI common stock (currently valued at $110 million, equal to approximately 19.75% of AMRI common stock); a seller note of $63 million; and the remainder in cash. Including Euticals, AMRI believes that it will have the financial strength to manage its increased debt and plans to de-lever based on a combination of EBITDA growth and/or principal re-payments.

AMRI has entered into debt financing commitments with JP Morgan and Barclays for amounts that are expected to be sufficient to provide funds necessary to consummate the transaction. In addition to the financing, the closing of the transaction is subject to customary closing conditions, including Hart-Scott-Rodino clearance in the U.S.

1EBITDA reflects IFRS with an adjustment to U.S. GAAP only for capitalization of R&D expenses

The 7 million shares of AMRI common stock (the "Shares") to be issued in connection with the transaction will be offered and sold outside the United States to Lauro 57, an eligible investor pursuant to Regulation S of the Securities Act of 1933, as amended (the "Securities Act").

The Shares have not been registered under the Securities Act, or the securities laws of any other jurisdiction, and may not be offered or sold in the United States absent registration under or an applicable exemption from such registration requirements. This press release does not constitute an offer to sell, or a solicitation of an offer to purchase, the Shares in any jurisdiction in which such offer or solicitation would be unlawful.

Nomura acted as exclusive financial advisor to AMRI in connection with this transaction and Goodwin Procter LLP and LCA Studio Legale acted as AMRI’s legal advisors. Lincoln International acted as sole financial advisor to Lauro 57, and Chiomenti Studio Legale and Debevoise & Plimpton LLP acted as Lauro 57’s legal advisors.

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, such as EBITDA, which is adjusted to exclude, among other things, the impact of interest income and expense, depreciation and amortization expense, and income tax expense or benefit. We exclude these items from the non-GAAP financial measures because they are outside our normal operations. There are limitations in using non-GAAP financial measures, as they are not prepared in accordance with generally accepted accounting principles, and may be different than non-GAAP financial measures used by other companies. In particular, we believe that the inclusion of supplementary non-GAAP financial measures in this press release helps investors to gain a meaningful understanding of our core operating results and future prospects without the effect of these often-one-time charges, and is consistent with how management measures and forecasts the company’s performance, especially when comparing such results to prior periods or forecasts. Non-GAAP results also allow investors to compare the company’s operations against the financial results of other companies in the industry who similarly provide non-GAAP results. The non-GAAP financial measures included in this press release are not meant to be considered superior to or a substitute for results of operations prepared in accordance with GAAP. It is not feasible to provide reconciliation to the most comparable projected U.S. GAAP measure because the excluded items are difficult to predict and estimate and are primarily dependent on future events.

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