On April 28, 2016 The PharmaMar Group reported 42.1 million euro in total revenues in the first quarter of 2016, of which 40 million euro were group net sales, 16% more than in the same period of 2015 (Press release, PharmaMar, APR 28, 2016, View Source [SID:1234511555]).

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Both the Biopharmaceutical and Consumer Chemicals divisions increased revenues in the quarter. Biopharmaceutical net sales amounted to 24.7 million euro, a 15% increase year-on-year. Of that figure, 22.8 million euro was net sales of Yondelis in the territories where PharmaMar is leads commercialisation. That was a 15% increase over the same period of 2015 and the highest quarterly sales of Yondelis since the drug was launched.

The Consumer Chemicals area reported 15.8 million euro in revenues in the period, an 18% increase year-on-year.
Other revenues in the first quarter included 1.8 million euro in royalties on Yondelis.
The schedule of milestone payments under the 2011 coordination agreement with Janssen L.P. concluded in 2015, and no revenues were recognised under this heading in 2016. Janssen L.P, launched Yondelis late in 2015 in the US following FDA approval and PharmaMar will begin to collect additional royalties on sales in the US.

Research and development expenditure continued to increase in 2016. The advanced status of the product pipeline and the fact that there are Phase III trials are under way or about to commence requires that the sizeable R&D expenditure of previous years be continued in 2016. Total spending on R&D and innovation 2 amounted to 18.7 million euro in the first quarter, compared with 12.6 million euro (net) in the same period of 2015.

This increase in R&D and innovation expenditure and the conclusion of the milestone payments resulted in group EBITDA being negative in the amount of -3.9 million euro, down from a positive 9.5 million euro in the first quarter of 2015, which included a milestone payment of 10 million dollars (8.8 million euro).

As a result, the Group reported an attributable net loss of -7.1 million euro (vs. +6.5 million euro in 1Q15).

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 28, 2016 Seattle Genetics, Inc. (NASDAQ: SGEN) reported financial results for the first quarter ended March 31, 2016 (Press release, Seattle Genetics, APR 28, 2016, View Source;p=RssLanding&cat=news&id=2162985 [SID:1234511558]). The company also highlighted ADCETRIS (brentuximab vedotin) commercialization, regulatory and clinical development accomplishments, vadastuximab talirine (SGN-CD33A; 33A) activities and progress with other proprietary pipeline programs and technologies.

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"In the first quarter, ADCETRIS net sales increased 20 percent compared to the first quarter of 2015, and we are completing three ongoing phase 3 trials designed to support additional label expansions. We expect top-line data from the first of these trials, ALCANZA, in the third quarter of this year, followed by ECHELON-1 in the 2017 to mid-2018 timeframe and ECHELON-2 in the 2017 to 2018 timeframe," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "With our pipeline, we remain on track to advance 33A into a phase 3 trial in acute myeloid leukemia (AML) by the third quarter, and we expect to report data from multiple programs over the course of 2016. Our strong financial position of more than $690 million in cash and investments at the end of March, and no debt, enables us to continue investing in our substantial opportunities to help people with cancer."

Recent ADCETRIS, Pipeline and Other Corporate Highlights

Achieved a $20 million one-time milestone payment from Takeda Pharmaceutical Company Limited (Takeda) triggered by Takeda surpassing ADCETRIS annual net sales of $200 million in its territory during 2015. The milestone was recognized as royalty revenue in the first quarter of 2016.
Takeda continues to receive additional marketing approvals for ADCETRIS, which is now commercially available in 64 countries worldwide following recent approvals in Russia and Egypt.
Initiated a phase 1/2 clinical trial of 33A in combination with azacitidine for patients with previously untreated myelodysplastic syndrome (MDS). MDS is often a precursor to AML, and both diseases broadly express CD33.
Reported research and preclinical data in multiple sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting highlighting antibody-drug conjugate (ADC) and other innovative targeted therapies, including:
Preclinical data supporting development activities with SGN-LIV1A and SEA-CD40;
Two novel preclinical programs, including an ADC for the treatment of multiple myeloma (SGN-CD352A) and a small molecule that enhances T-cell-mediated antitumor activity (2-fluorofucose; 2FF);
Data showing the ability of auristatin-based ADCs, including ADCETRIS, to initiate immunogenic cell death, supporting evaluation of ADCs in combination with checkpoint inhibitors; and,
A new auristatin-based drug-linker as well as several novel linkers that expand Seattle Genetics’ proprietary ADC technology platform and may enable conjugation with previously inaccessible cytotoxic payloads.
Initiated a phase 1 clinical trial of SGN-CD19B for relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL) and grade 3 follicular lymphoma. SGN-CD19B is an anti-CD19 ADC utilizing the same ADC technology as 33A, which includes a highly potent cytotoxic DNA-crosslinking agent called a pyrrolobenzodiazepine (PBD) dimer linked via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb).
Generated fees from ongoing ADC collaboration with Genentech upon its extension of the research term and renewal of exclusive licenses to specific ADC targets.
Added to and promoted several members of the senior management team, including:
Promoting Darren Cline to Executive Vice President, Commercial. Mr. Cline has been with Seattle Genetics since November 2010. During his tenure, he has been an integral member of the commercial leadership team, including significant contributions in the successful launch and ongoing commercialization of ADCETRIS in the United States and Canada.
Hiring Brandi Robinson as Senior Vice President, Corporate Communications. Ms. Robinson previously spent four years as Vice President and Head of Communications, North America for Sanofi. Before that, she was at Novartis for more than a decade.
Hiring Christopher Thomson, Ph.D., as Vice President, Commercial Planning. Dr. Thomson will oversee the company’s new European operations. He previously spent eight years at Astellas Pharma Europe, most recently as Vice President, Head of Oncology Business Unit. Prior to that, he spent three years with IMS Health and eight years with Bayer.
Promoting Kristin Rand to Vice President and Compliance Officer. Since joining Seattle Genetics in October 2012, Ms. Rand has grown the company’s compliance program to ensure its integrity, ethics and compliance with applicable laws and regulations.
Anticipated Upcoming Activities

ADCETRIS

Report data in the third quarter of 2016 from the phase 3 ALCANZA trial in patients with relapsed CD30-expressing cutaneous T-cell lymphoma (CTCL).
Report data in the 2017 through mid-2018 timeframe from the phase 3 ECHELON-1 trial in frontline classical Hodgkin lymphoma.
Complete enrollment in the phase 3 ECHELON-2 trial in frontline mature T-cell lymphoma (MTCL) during 2016 and report data in the 2017 to 2018 timeframe.
ADCETRIS is not currently approved for use in CTCL, frontline MTCL or frontline Hodgkin lymphoma.

Vadastuximab Talirine (SGN-CD33A)

Initiate a phase 3 trial to evaluate 33A in combination with hypomethylating agents, or HMAs, in older patients with AML by the third quarter of 2016.
Report additional data from a phase 1 trial of 33A in combination with HMAs at the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting being held June 9 to 12, 2016 in Copenhagen, Denmark.
Report data in 2016 from a phase 1b trial of 33A in combination with cytarabine and daunorubicin for frontline, younger AML patients.
More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.

Additional Pipeline Programs

Initiate a randomized phase 2 trial of denintuzumab mafodotin (SGN-CD19A; 19A) in frontline DLBCL in the first half of 2016.
Report phase 1 clinical data from ASG-15ME and ASG-22ME at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting being held June 3 to 7, 2016 in Chicago, Illinois. These programs are in development for solid tumors, notably bladder cancer, under a 50:50 co-development collaboration with Astellas.
Initiate a phase 1 trial of SGN-CD123A in AML during 2016.
Advance SGN-CD352A, a novel ADC for multiple myeloma, into a phase 1 clinical trial. Preclinical data were reported at AACR (Free AACR Whitepaper) on this novel ADC, which is composed of an anti-CD352 antibody utilizing the company’s PBD and EC-mAb technology.
First Quarter 2016 Financial Results

Total revenues in the first quarter of 2016 were a record $111.2 million, an increase of 35 percent over first quarter 2015 revenues of $82.2 million. Revenues in the first quarter of 2016 included:

ADCETRIS net product sales of $58.6 million, a 20 percent increase from net product sales of $48.9 million for the first quarter of 2015.
Royalty revenues of $32.3 million on international sales of ADCETRIS by Takeda, compared to $11.1 million for the same period in 2015. First quarter 2016 royalty revenues included a $20 million one-time milestone payment triggered by Takeda surpassing ADCETRIS annual net sales of $200 million in its territory during 2015.
Amounts earned under the company’s ADCETRIS and ADC collaborations totaling $20.2 million in the first quarter of 2016, compared to $22.2 million in the first quarter of 2015.
Total costs and expenses for the first quarter of 2016 were $132.2 million, compared to $103.9 million for the first quarter of 2015. The planned increase in 2016 costs and expenses was primarily related to progress with ADCETRIS and investment in the company’s pipeline programs, including expanded 33A clinical development and manufacturing activities.

Non-cash, share-based compensation cost for the first quarter of 2016 was $12.2 million, compared to $7.7 million for the first quarter of 2015.

Net loss for the first quarter of 2016 was $20.5 million, or $0.15 per share, compared to a net loss of $21.7 million, or $0.17 per share, for the first quarter of 2015.

As of March 31, 2016, Seattle Genetics had $691.7 million in cash, cash equivalents and investments, compared to $712.7 million as of December 31, 2015.

On April 28, 2016 Agenus Inc. (NASDAQ:AGEN), an immuno-oncology company developing checkpoint antibodies and cancer vaccines, reported a corporate update and reported financial results for the first quarter ended March 31, 2016 (Press release, Agenus, APR 28, 2016, View Source [SID:1234511561]).

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"In the first quarter we advanced our checkpoint antibodies by gaining FDA clearance for the Investigational New Drug applications for our CTLA-4 antagonist antibody AGEN1884, and for our GITR agonist antibody partnered with Incyte, INCAGN1876," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "Earlier this week, we commenced a Phase 1 trial of AGEN1884 in solid tumors with the first patient in the trial having been dosed. During the remainder of 2016, we expect to begin clinical trials for additional checkpoint antibody candidates. Our plans this year and into next include initiating one or more randomized trials with Prophage, including combination trials with approved and/or experimental immunotherapeutic agents. Within the next 12 months we also plan to initiate a Phase 1 trial of our AutoSynVax or ASV vaccine, a synthetic autologous vaccine candidate that targets cancer neoantigens. Finally, we expect to consummate non-dilutive funding strategies and evaluate additional strategic alliances and partnerships to strengthen our immuno-oncology capabilities."

First Quarter 2016 and Recent Corporate Highlights

April: Initiated Phase 1 trial of AGEN1884, a CTLA-4 antagonist antibody, in solid tumors. AGEN1884 is the first of a series of checkpoint antibodies the Company is developing. AGEN1884 was developed using Agenus’ powerful in-house antibody technology platform.
April: Presented preclinical data for three checkpoint antibody programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference: INCAGN1949 (an OX40 agonist antibody, partnered on a 50/50 financial basis with Incyte), INCAGN1876 (an agonist antibody for the glucocorticoid-induced TNFR-related protein, or GITR, also partnered on a 50/50 basis with Incyte), and our anti-CTLA-4 program (AGEN1884 and AGEN2041, partnered with Recepta for certain South American territories). The poster presentations covered preclinical pharmacology for each antibody, including detailed studies to support potential in vivo mechanism(s) of action. Data from the INCAGN1949 and INCAGN1876 programs will also be presented at the upcoming Protein and Antibody Engineering Summit (PEGS) in Boston tomorrow, April 29.
January: Investigational New Drug applications received clearance from the U.S. Food and Drug Administration for two checkpoint antibodies: AGEN1884 (CTLA-4 antagonist) and INCAGN1876 (GITR agonist partnered with Incyte).
January: Began integration efforts for our antibody manufacturing facility acquired from Xoma in December 2015. The facility will enable the Company to manufacture checkpoint antibodies for its own programs and those of its collaborators. The facility is expected to provide Agenus’ antibody supply requirements for most programs through clinical proof-of-concept studies.
First Quarter 2016 Financial Results

For the first quarter ended March 31 2016, Agenus reported a net loss attributable to common stockholders of $31.8 million, or $0.37 per share, basic and diluted, including $9.6 million in non-cash expenses. This compares to a net loss attributable to common stockholders for the first quarter of 2015 of $18.8 million, or $0.28 per share, basic and diluted. The increase in net loss attributable to common stockholders for the three months ended March 31, 2016, compared to the net loss attributable to common stockholders for the same period in 2015, was primarily due to the advancement of our checkpoint programs.

Cash, cash equivalents and short-term investments were $148.2 million as of March 31, 2016.

On April 28, 2016 BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) reported financial results for the first quarter ended March 31, 2016 (Press release, BioMarin, APR 28, 2016, View Source [SID:1234511564]). Non-GAAP net loss was $27.2 million for the quarter ended March 31, 2016, compared to non-GAAP net loss of $25.4 million for the first quarter of 2015. GAAP net loss was $85.1 million, or $0.53 per basic and diluted share for the first quarter of 2016, compared to GAAP net loss of $67.5 million, or $0.43 per basic and diluted share, for the first quarter of 2015.

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Total BioMarin Revenue was $236.7 million for the first quarter of 2016, an increase of 16.7% compared to the same period in 2015. This strong result was driven by year over year growth of 43.5% and 53.2% of Vimizim and Kuvan, respectively. Kuvan revenue from ex-North America territories since BioMarin acquired worldwide rights in January 2016 contributed $16.9 million and revenues in North America contributed $60.0 million in the quarter. Naglazyme patient growth was 8.5% compared to a year ago, the 40th straight quarter since the product was launched in 2005. Naglazyme revenue in the first quarter 2016 was lower than revenue in the first quarter 2015 primarily due to the timing of central government orders from Latin America.

As of March 31, 2016, BioMarin had cash, cash equivalents and investments totaling $771.3 million, as compared to $1,018.3 million on December 31, 2015.

Commenting on the quarter, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin said, "Our commercial base business is robust and is expected to generate over one billion dollars in revenues this year. Prospects for new product launches in 2017 increased during the quarter due to positive data readouts for cerliponase alfa and pegvaliase that we expect will lead to two new product filings later this year. In addition, at our recent Research and Development Day for analysts and investors, we highlighted very encouraging preliminary data from our gene therapy product BMN 270 for hemophilia A and robust 12 month data with vosoritide for achondroplasia. If the data from these programs continue to mature as we hope, we believe that these products could each ultimately drive a billion dollars in revenue when commercialized. Finally, we continue to expect to manage this growing business with the goal of achieving non-GAAP break-even or better in 2017 regardless of the regulatory outcome of Kyndrisa in Europe."

Net Product Revenue (in millions of U.S. dollars, unaudited)

Total Revenue

Three Months Ended March 31,
2016 2015 $ Change % Change

Vimizim (1) $ 72.6 $ 50.6 $ 22.0 43.5 %
Naglazyme (1) 65.4 78.2 (12.8 ) (16.4 )%
Kuvan (2) 76.9 50.2 26.7 53.2 %
Aldurazyme 16.4 18.2 (1.8 ) (9.9 )%
Firdapse 4.1 4.1 - 0.0 %
Net product revenues 235.4 201.3 34.1 16.9 %

Collaborative agreement revenues 0.2 0.4 (0.2 )
Royalty, license and other revenues 1.1 1.2 (0.1 )
Total BioMarin revenues $ 236.7 $ 202.9 $ 33.8 16.7 %

(1) Vimizim and Naglazyme revenues experience quarterly fluctuations primarily due to the timing of government ordering patterns in certain countries. The Company does not believe these fluctuations reflect a change in underlying demand.
(2) Growth in North America contributed $60.0 million in the first quarter with an additional $16.9 million coming from newly acquired ex-North American territories.

Reconciliation of Aldurazyme Revenues

Three Months Ended March 31,
2016 2015 $ Change % Change
Aldurazyme revenue reported by Genzyme $ 52.8 $ 53.4 $ (0.6 ) (1.1 )%

Three Months Ended March 31,
2016 2015 $ Change
Royalties earned from Genzyme $ 21.5 $ 22.3 $ (0.8 )
Net product transfer revenues (3) (5.1 ) (4.1 ) (1.0 )
Total Aldurazyme net product revenues $ 16.4 $ 18.2 $ (1.8 )

(3) To the extent units shipped to third party customers by Genzyme exceed BioMarin inventory transfers to Genzyme, BioMarin will record a decrease in net product revenue from the royalty payable to BioMarin for the amount of previously recognized product transfer revenue. If BioMarin inventory transfers exceed units shipped to third party customers by Genzyme, BioMarin will record incremental net product transfer revenue for the period. Positive net product transfer revenues result in the period if BioMarin transferred more units to Genzyme than Genzyme sold to third-party customers.

2016 Financial Guidance

Revenue Guidance ($ in millions)

Item
Provided
February 25, 2016 Updated April 28, 2016
Total BioMarin Revenues $1,050 to $1,100 Unchanged
Vimizim Net Product Revenue $300 to $330 $315 to $340
Naglazyme Net Product Revenue $290 to $320 Unchanged
Kuvan Net Product Revenue $320 to $350 Unchanged

Select Income Statement Guidance ($ in millions, except percentages)

Item
Provided
February 25, 2016 Updated April 28, 2016
Cost of Sales (% of Total Revenue) 18.0% to 19.0% Unchanged
Selling, General and Admin. Expense $470 to $490 Unchanged
Research and Development Expense $680 to $720 Unchanged
Non – GAAP Net Loss $(75) to $(100) Unchanged
GAAP Net Loss $(400) to $(430) $(355) to $(385)*

*GAAP Net Loss guidance updated April 28, 2016 based on impact of final purchase accounting treatment for the PKU franchise acquisition from Merck that closed in the first quarter 2016.

Key Program Updates at R&D Day April 20, 2016

BMN 270 gene therapy product for hemophilia A: The Company provided encouraging preliminary data from an ongoing Phase 1/2 clinical trial with BMN 270, an investigational gene therapy treatment for hemophilia A. A total of eight patients with severe hemophilia A received a single dose of BMN 270, six of whom have been treated at the highest dose of 6 x 1013 vector genomes (VG)/kilogram (kg), and to date, post-treatment follow-up ranges from five to 16 weeks. As stated at R&D Day, patients at the highest dose experienced increasing Factor VIII activity levels ranging between 4% and 60% (as a percentage of normal calculated based on the numbers of International Units (IU) per milliliter of whole blood), with five of six patients treated at the high dose now over 5% and two of six at over 50%. All high dose patients improved from severe to either moderate, mild or normal range in terms of factor levels based on World Federation of Hemophilia criteria. (See BioMarin press release from April 20, 2016 for further details.)

Vosoritide for achondroplasia: The Company provided an update on its Phase 2 study of vosoritide, an analog of C-type Natriuretic Peptide (CNP), in children with achondroplasia, the most common form of dwarfism. After 12 months of daily dosing at 15 µg/kg/day, the cohort 3 patients (n=10) experienced a 46% or 1.9 cm/year increase in mean annualized growth velocity from baseline (p-value = 0.02). These findings provide evidence of durability of effect consistent with previously presented 6-month data for these patients, which demonstrated an annualized increase of 50% or 2.0 cm/year in mean annualized growth velocity. In addition, 6-month data for 12 patients who were initiated on a lower dose and switched to 15 µg/kg/day showed an increase of 65% or 2.3 cm/year in mean annualized growth velocity from baseline (p-value = 0.002). (See BioMarin press release from April 20, 2016 for further details.)

Cerliponase alfa for CLN2, late-infantile form of Batten disease: Complete results from the Phase 1/2 study of cerliponase alfa, a recombinant human tripeptidyl peptidase 1 (rhTPP1), for the treatment of patients with late-infantile neuronal ceroid lipofuscinosis type 2 (NCL-2), a form of Batten disease were announced at the WORLD LSD Symposium on March 2, 2016. Based on the robust data results announced at that meeting, the Company shared plans to submit in the U.S. and E.U. for regulatory approval mid-year 2016. (See BioMarin press release from March 2, 2016 for further details.)

Pegvaliase for phenylketonuria (PKU): Pivotal results for the Phase 3 PRISM-2 study (formerly referred to as 165-302) that pegvaliase met the primary endpoint of change in blood Phe compared with placebo (p<0.0001) were announced March 21, 2016. The pegvaliase treated group maintained mean blood Phe levels at 527.2 umol/L compared to their RDT baseline of 503.9 umol/L, whereas the placebo treated group mean blood Phe levels increased to 1385.7 umol/L compared to their RDT baseline of 536.0 umol/L. The treatment effect demonstrated in this study represents an approximately 62% improvement in blood Phe compared to placebo. Based on the supportive data results, the Company plans to submit a Biologics License Application (BLA) to U.S. FDA in the second half of 2016. (See BioMarin press release from March 21, 2016 for further details.)