On October 26, 2017 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported financial results for the third quarter ended September 30, 2017 (Press release, BioMarin, OCT 26, 2017, View Source [SID1234521209]).

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For the quarter ended September 30, 2017, GAAP Net Loss was $(12.5) million, or $(0.07) per basic and diluted share, compared to GAAP Net Loss of $(37.4) million, or $(0.22) per basic and diluted share for the quarter ended September 30, 2016. The reduction in GAAP Net Loss year over year was primarily due to the $31.5 million net upfront license payment received as a result of the License and Settlement Agreements entered into with Sarepta Therapeutics Inc. in July 2017. The decreased GAAP Net Loss was also driven by increased net product revenues for Kuvan and Vimizim, partially offset by a decrease in the Benefit From Income Taxes, and increased Selling, General and Administrative expenses for Kuvan, Brineura and Vimizim. BioMarin also announced today that full year GAAP net loss guidance is being reduced to between ($110) million and ($130) million.

Non-GAAP Income for the third quarter ended September 30, 2017 was $7.8 million, compared to Non-GAAP Income of $2.9 million for the quarter ended September 30, 2016. BioMarin also announced today that full year Non-GAAP Income guidance is being increased to between $60 million and $80 million.

Total Revenues were $334.1 million for the third quarter of 2017, and were $955.3 million for the nine months ended September 30, 2017, an increase of 19% and 17% respectively compared to the same periods in 2016. For the nine months ended September 30, 2017, Kuvan net product revenues increased 16% year over year. Growth was driven by a 9% increase in the number of commercial patients on Kuvan therapy in the U.S and the continued growth in the ex-North American territories acquired in 2016. For the nine months ended September 30, 2017, Naglazyme net product revenues increased by 8% year over year, due primarily to an increase of 7% in the number of Naglazyme commercial patients. Vimizim net product revenues increased 15% year over year during the nine months ended September 30, 2017. The number of Vimizim commercial patients increased 23% year over year.

On October 18, 2017, the Company commented on its Total Revenue and Non-GAAP Income (Loss) trends for the third quarter and full-year 2017. In terms of the overall commercial business, BioMarin stated that sales of products in markets throughout most of the world are performing at or above internal expectations. However, the Company said the one exception is Brazil, where a slowdown in federal purchasing orders had extended into the third quarter of this year. As a result, third quarter revenues were negatively impacted. Since October 18, the Brazilian Ministry of Health has initiated their purchasing process which is expected to result in net product revenue from Brazil in the fourth quarter. Based on this order Total Revenues for full-year 2017 are confirmed to be within prior guidance.

As of September 30, 2017, BioMarin had cash, cash equivalents and investments totaling approximately $1.7 billion, as compared to $1.4 billion on December 31, 2016.

Commenting on the quarter, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, said, “We achieved a number of important strategic milestones so far this year, including record Total Revenues in the third quarter and the go ahead from both U.S. and U.K. health authorities to begin Phase 3 studies with valoctocogene roxaparvovec (formerly referred to as BMN 270) gene therapy program for severe hemophilia A by year-end.” Mr. Bienaimé continued, “We had many significant updates at our recent R&D Day, including the announcement of our next IND candidate BMN 290 for Freidriech’s Ataxia, a rare neurologic disorder that affects nearly 15,000 people worldwide. We were also pleased to share that vosoritide for achondroplasia demonstrated a sustained increase in annualized growth rate at 30 months of treatment. For pegvaliase, we anticipate FDA action on our Biologics License Application in the first half of 2018, as well as our planned submission of the Marketing Authorization Application in Europe in the first quarter of 2018. With these programs all advancing, supported by our strong base commercial business, we have reduced our GAAP Net Loss guidance and increased our Non-GAAP Income guidance for the full-year 2017.”

Key Program Updates at R&D Day October 18, 2017

BMN 290 for Freidriech’s Ataxia (FA): BioMarin announced that it has selected as its next drug development candidate, BMN 290, a selective chromatin modulation therapy intended for treatment of FA. FA is a rare autosomal recessive disorder with worldwide prevalence of approximately 15,000, which results in disabling neurologic and cardiac progressive decline. Currently there are no approved disease modifying therapies for FA. In preclinical models, BMN 290 increases frataxin expression in affected tissues more than two-fold. BMN 290 is a second-generation compound derived from a compound the Company acquired from Repligen Corporation (Repligen) that had human clinical data demonstrating increases in frataxin in FA patients. The Company selected BMN 290 for its favorable penetration into the central nervous system and cardiac target tissues, and its preservation of the selectivity of the original Repligen compound. The Company expects to submit the IND application for BMN 290 in the second half of 2018.

Valoctocogene roxaparvovec (formerly referred to as BMN 270) gene therapy for hemophilia A: BioMarin announced today that it had been granted Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for valoctocogene roxaparvovec. The designation is intended to expedite the development and review of medicines to treat a serious disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. The Company also announced that the 6e13 vg/kg dose and 4e13 vg/kg dose had been cleared by both U.S. and U.K. health authorities to begin Phase 3 studies.

The protocol for each Phase 3 study, one using the 6e13 vg/kg dose and one using the 4e13 vg/kg dose, will likely include approximately 40 patients for a duration of 52 weeks per study. The Company expects to file for approval of valoctocogene roxaparvovec with 52-week data from the Phase 3 studies. BioMarin expects to initiate the global Phase 3 program in the fourth quarter of 2017, complete enrollment of the last patient by the end of 2018 and provide top-line Phase 3 data by the end of 2019.

At R&D Day, the Company provided an update on the ongoing open-label Phase 1/2 study of the 4e13 vg/kg dose at up to 36 weeks of observation at the September 14, 2017 data cut. Since the last data update provided during the second quarter earnings call on August 2, 2017, five of the six patients at the 4e13 vg/kg dose tracked to the low range of normal, and the sixth is in the mild range for Factor VIII levels. Median annualized bleed and factor VIII use rates for 4e13 and 6e13 vg/kg were zero after Week 4.

The World Health Organization (WHO) has approved, and BioMarin was issued, the International Nonproprietary Name (INN) “valoctocogene roxaparvovec” for the Company’s gene therapy to treat hemophilia A. INNs identify pharmaceutical substances or active pharmaceutical ingredients. Each INN is a unique name that is globally recognized and is public property. A nonproprietary name is also known as a generic name.

BioMarin has commissioned its gene therapy manufacturing facility, located in Novato, California. Good Manufacturing Practices (GMP) production of valoctocogene roxaparvovec has commenced and is intended to support clinical development activities and anticipated commercial demand, upon product approval. This facility is capable of supporting the manufacturing of product for approximately 2,000 patients per year, and the production process was developed in accordance with International Conference on Harmonisation guidance for Pharmaceuticals for Human Use facilitating worldwide registration with health authorities.

Pegvaliase for phenylketonuria (PKU): BioMarin announced that the pegvaliase Biologics License Application (BLA) remains on track for FDA action during the first half of 2018. The Company plans to submit a Marketing Authorization Application to the European Medicines Agency in the first quarter of 2018. Pegvaliase is a PEGylated recombinant phenylalanine ammonia lyase enzyme product that reduces blood phenylalanine (Phe) levels in adult patients with PKU who have uncontrolled blood Phe levels on existing management.

Vosoritide for achondroplasia: BioMarin provided an update on its open-label Phase 2 study of vosoritide, an analog of C-type Natriuretic Peptide (CNP), in children with achondroplasia, the most common form of disproportionate short stature in humans.

Vosoritide for achondroplasia has demonstrated sustained increase in average growth velocity over 30 months of treatment in 10 children, who completed 30 months of daily dosing at 15 µg/kg/day. Over this period of time, patients experienced mean absolute growth increase of approximately 4 cm over what their baseline growth velocity would have predicted.

The sustained increase in annualized growth velocity was accompanied by sustained improvements over time in height compared to age- and gender-matched unaffected children as measure by z-scores. In addition, treatment with vosoritide shows continued improvement over time in proportionality as measured by a ratio of the upper and lower body measurements, or U/L ratio.

The ongoing, global Phase 3 study is a randomized, placebo-controlled study of vosoritide in approximately 110 children with achondroplasia ages 5-14 for 52 weeks. The study will be followed by a subsequent open-label extension. Children in this study will have completed a minimum six-month baseline study to determine their respective baseline growth velocity prior to entering the Phase 3 study. Vosoritide is being tested in children in the age range where their growth plates are still open. This is approximately 25 percent of people with achondroplasia. The Company expects to complete enrollment of the Phase 3 study in mid-2018 and provide top-line data in the second half of 2019.

Given the importance of early intervention in this indication, at R&D Day, the Company announced that it will begin an infant/toddler study in the first half of 2018 in children ages 0-5 years old.

BMN 250 for MPS IIIB (Sanfilippo Syndrome, Type B): The Company discussed preliminary results from the Phase 1/2 trial with BMN 250 that demonstrated reduced heparan sulfate (HS) levels, a biomarker in the cerebrospinal fluid (CSF), in the brains of affected children. BMN 250, is an investigational enzyme replacement therapy using a novel fusion of recombinant human alpha-N-acetylglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor 2 (IGF2), for the treatment of Sanfilippo B syndrome or mucopolysaccharidosis IIIB (MPS IIIB). Discovered by BioMarin, BMN 250 is being studied in a multicenter, international clinical trial evaluating safety and tolerability, as well as cognitive function of patients with Sanfilippo B receiving BMN 250. Designed to restore functional NAGLU activity in the brain, BMN 250 is administered via intracerebroventricular (ICV) infusion.

In the completed dose escalation portion of the study (Part 1), which was primarily designed to determine safety and pharmacodynamic activity of BMN 250, three patients received escalating doses (30mg, 100mg, 300mg) of BMN 250 over 9 to12 months. CSF HS levels, which were markedly elevated at baseline, were reduced to the non-affected or normal range in all three patients, whether assessed as total or disease-specific HS. Sanfilippo B patients are missing one of four enzymes for HS degradation.

In those same patients, abdominal MRI scans showed significantly enlarged liver size at baseline followed by rapid decreases in liver size into the normal range for age with BMN 250 treatment, suggesting that ICV-administered BMN 250 reaches the peripheral circulation and may have activity in somatic organs. In contrast, most Sanfilippo B patients enrolled in BioMarin’s concurrently-running observational study (250-901) had increased liver size at baseline and experienced further increases in liver size over time. Two of the three treated patients from the dose escalation arm showed stabilization or some improvement compared to their pre-dose baselines in cognitive Development Quotient (DQ), a measure of cognitive function normalized to age. Patients with untreated Sanfilippo B usually show progressive decline in DQ.
Conference Call Details

BioMarin will host a conference call and webcast to discuss third quarter 2017 financial results today, Thursday, October 26, 2017 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.

U.S. / Canada Dial-in Number: 866.502.9859
International Dial-in Number: 574.990.1362
Conference ID: 96054850

Replay Dial-in Number: 855.859.2056
Replay International Dial-in Number: 404.537.3406
Conference ID: 96054850

On October 26, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported new positive results for EndoPredict, a second-generation prognostic gene expression test for breast cancer (Press release, Myriad Genetics, OCT 26, 2017, View Source [SID1234521201]). The study found that EndoPredict (EPclin) was superior to the first-generation Oncotype DX Breast Recurrence Score (RS) in predicting breast cancer recurrence in women determined to be at intermediate clinical risk by Nottingham Prognostic Index. The data will be presented at the 3rd World Congress on Controversies in Breast Cancer (CoBrCa) being held Oct. 26-28, 2017 in Tokyo, Japan.

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This is the second head-to-head study to show that EndoPredict significantly outperformed the first-generation prognostic test for breast cancer, especially for predicting the distant recurrence of breast cancer, and underscores Myriad’s unwavering commitment to advancing precision medicine for women with breast cancer. The first study was published in the Journal of the National Cancer Institute (JNCI) in July 2016.

“This new study is further evidence that compared to the first generation test, EndoPredict more effectively predicts the recurrence of breast cancer up to 10 years after diagnosis in women with ER+, HER2- breast cancer,” said Ivana Sestak, Ph.D., principal investigator, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London. “These findings will help physicians personalize treatment for women with an intermediate clinical risk of recurrence by identifying those patients who need adjuvant chemotherapy following surgery.”

Oral Presentation.
Title: Comparison of prognostic performance of Oncotype Dx Recurrence Score versus EndoPredict (EPclin) in women with intermediate risk of recurrence by Nottingham Prognostic Index.
Presenter: Ivana Sestak, Ph.D.
Date: Friday, Oct. 27 3:30 to 4:30 p.m.
Programme Number: OR01.

The analysis included 387 women with ER-positive, HER2-negative breast cancer and who were determined to be at intermediate risk of recurrence as defined by the Nottingham Prognostic Index (NPI). The primary endpoint was distant recurrence and the primary objective was to assess the value of EndoPredict (EPclin) for the prediction of (late) distant recurrence and compare the results to Oncotype Recurrence Score (RS).

This study showed that EndoPredict markedly outperformed Oncotype across the 10-year follow-up period with prognostic power more than two times higher (EPclin: LRX2= 14.1; RS: LRX2=5.9).

In this analysis, EndoPredict stratified 149 (38.5 percent) women into the low risk group and 238 (61.5 percent) into the high risk group. A highly significant separation between the groups was observed. The 10-year distant recurrence (DR) was 12.5 percent for the low risk group vs. 25.9 percent for the high risk group (HR=2.42). However, for Oncotype, the DR rate was 16.3 percent for the low risk group and no clear separation between intermediate and high risk groups was observed, with similar 10-year distant recurrence risks (24.2 vs. 27.3 percent, respectively).

Additionally, for the prediction of late distant recurrence (5-10 years), EndoPredict provided significant prognostic value in this time period and identified 136 (40.2 percent) patients as low risk and 202 (59.8 percent) as high risk, while the first generation test did not provide prognostic value for late metastasis for women deemed intermediate risk of recurrence by NPI. These results confirm the importance of the inclusion of clinicopathological data to achieve best prognostication in this patient group.

Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #CoBrCa.

About EndoPredict
EndoPredict is a second-generation, multigene prognostic test for patients diagnosed with breast cancer. The test provides physicians with information to devise personalized treatment plans for their patients. EndoPredict has been validated in approximately 4,000 patients with node-negative and node-positive cancer and has been used clinically in over 13,000 patients. In contrast to first-generation multigene prognostic tests, EndoPredict detects the likelihood of late metastases (i.e., metastasis formation after more than five years) and, therefore, can guide treatment decisions regarding the need for chemotherapy, as well as extended anti-hormonal therapy. Accordingly, therapy decisions backed by EndoPredict confer a high level of diagnostic safety. For more information, please visit: www.endopredict.com.

On October 26, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, and the NSABP Foundation, Inc. (NSABP), an academic research organization supported by the National Cancer Institute (NCI) and industry funding, reported that they have entered into a research agreement to jointly characterize the immunophenotypes of colorectal cancer samples using the PanCancer IO 360 Gene Expression Panel, a highly-multiplexed gene expression panel designed to identify targetable pathways of tumor and immune biology (Press release, NanoString Technologies, OCT 26, 2017, View Source [SID1234521189]).

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Under this collaborative agreement, NanoString and the NSABP will use the NanoString nCounter Analysis System to study colorectal cancer tumor samples from the NSABP biobank. The NSABP’s MPR-1 Patient Registry and Biospecimen Profiling Repository is a bank of over 2,500 tumor tissue specimens collected from patients with metastatic colorectal cancer. The comprehensive characterization of the tumor-immune microenvironment in the NSABP samples has the potential to identify novel biomarkers for different mechanisms of immune evasion in colorectal tumors.

The PanCancer IO 360 Panel assays key pathways from the tumor, the microenvironment and the immune system and includes more than 20 signatures that are potentially associated with therapeutic response to novel therapeutic agents with “matched” mechanisms of action. These signatures include defective DNA mismatch repair (dMMR) – the genetic abnormality causing high microsatellite instability (MSI-H), which is particularly relevant in this tumor type and is associated with high response to PD-1/PD-L1 blockade. Interrogation of colorectal tumor samples from the NSABP repository with the PanCancer IO 360 Panel will test the concordance between dMMR status as assessed by the NanoString PanCancer IO 360 Panel and the standard immunohistochemistry (IHC) approach.

The collaborators will use the PanCancer IO 360 Panel to explore biological pathways of immune resistance including NanoString’s Tumor Inflammation Signature (TIS), recently described by Ayers, et al. (View Source), which measures the presence or absence of a peripherally suppressed adaptive immune response within the tumor. For example, TIS was found to be predictive of response to pembrolizumab, and pembrolizumab’s mechanism of action is believed to unleash a pre-existent adaptive immune response by inactivating the inhibitory activity of this receptor. NanoString and NSABP hypothesize that the Tumor Inflammation Signature (TIS) could identify a larger population of tumors potentially responsive to PD-1 blockade than MSI/dMMR status alone, because the TIS directly measures downstream tumor inflammation that can result from multiple different mechanisms (in addition to high mutation load).

“Anti-PD-1 and anti-PD-L1 antibodies have demonstrated significantly durable efficacy in patients with metastatic MSI-H colorectal cancer. Unfortunately, this subset of patients represents only about 5% of stage IV CRC patients, leaving the vast majority of this population in great need of effective treatments,” said Alessandra Cesano, chief medical officer at NanoString. “The combination of NanoString’s powerful technology and the NSABP’s expertise and extensive research biobank of colorectal tumor samples holds great promise for the discovery of new targets that will help us to fight this devastating disease.”

“It is critical to find better ways of identifying colorectal cancer patients who will benefit from current immunotherapeutic approaches as well as improving our understanding of the mechanisms of resistance at the molecular level,” said Dr. Samuel Jacobs, Director of Medical Affairs for the NSABP. “It is our hope that this collaboration with NanoString will deepen our understanding of the mechanisms of tumor immune evasion in order to guide the successful development of novel immunotherapeutic approaches and combinations.”

On October 26, 2017 Ipsen (Euronext: IPN; ADR: IPSEY), a global specialty-driven biopharmaceutical group, reported sales for the third quarter of 2017 (Press release, Ipsen, OCT 26, 2017, View Source [SID1234521180]).

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Financial highlights

Q3 2017 Group sales growth of 22.6%1 driven by Specialty Care sales growth of 26.5%1 reflecting continued Somatuline momentum and increasing contribution of new products Cabometyx and Onivyde, and solid Consumer Healthcare sales growth of 5.0%1
YTD Group sales growth of 20.1%1 fueled by Specialty Care sales growth of 24.3%1 and Consumer Healthcare back to growth at 2.5%1
Full Year 2017 guidance confirmed: Specialty Care sales growth greater than 24%1, Consumer Healthcare back to growth1 and a Core Operating Income margin greater than 25% of net sales
Recent pipeline highlights

Approval of Somatuline by FDA2 for the treatment of carcinoid syndrome in the U.S.
Approval of Xermelo by EMA2 for the treatment of carcinoid syndrome diarrhea in combination with SSA2 therapy
Validation by EMA2 of the application of Cabometyx for the addition of a new indication in first-line treatment of advanced renal cell carcinoma (RCC)
Phase 3 CELESTIAL trial of cabozantinib meets primary endpoint of overall survival in patients with advanced hepatocellular carcinoma
Key figures

Third quarter and nine months 2017 unaudited IFRS consolidated sales

1st table



David Meek, Chief Executive Officer of Ipsen stated: “The excellent performance in the third quarter reflects the continued execution against our 2017 objectives with an accelerated momentum of our Specialty Care business. We achieved several important pipeline milestones during the quarter, notably in Oncology, further strengthening our leadership position in the neuroendocrine tumor market and increasing the potential value of the Cabometyx franchise. We remain focused on the launch execution of our new products and building an innovative and sustainable pipeline.”



Third quarter 2017 sales highlights

Note: Unless stated otherwise, all variations in sales are stated excluding foreign exchange impacts.

Third quarter 2017 unaudited IFRS consolidated sales

2d table



Consolidated Group sales grew 22.6% to €470.1 million.

Sales of Specialty Care products reached €396.2 million, up 26.5% year-on-year.

Somatuline sales reached €173.0 million, up 29.9%, year-on-year, driven by the continued excellent growth in the United States, and by strong performance in Europe, notably in the UK, Germany and France.

Decapeptyl sales reached €88.2 million, up 6.4% year-on-year, supported by strong volume growth in China despite some pricing pressure as well as good sales trends in France and Spain.

Cabometyx sales reached €14.3 million, driven primarily by the performance in France and Germany and also in the Netherlands and in the UK.

Onivyde sales reached €17.9 million, stable versus the second quarter.

Dysport sales reached €77.4 million, up 6.1% year-on-year, led by a solid performance in the United States, notably in aesthetics through the Galderma partnership (despite some unfavorable phasing of shipments) and in the Middle East.

Consumer Healthcare product sales totaled €73.9 million, up 5.0% year-on-year, supported by the good performance of Tanakan in Russia, as well as Bedelix and Forlax in Algeria, offset by a new contractual set up in China which started to impact Etiasa in the third quarter.

Smecta sales reached €23.3 million, down 6.4% year-on-year, mainly affected by a negative stocking impact in China and the performance in Russia.

Forlax sales reached €10.4 million, up 16.7% year-on-year, positively impacted by a favorable basis of comparison in Algeria where import programs were suspended in the third quarter of 2016.

Tanakan sales reached €11.2 million, up 24.7% year-on-year, driven by a rebound of sales in Russia as compared to 2016 which was impacted by challenging market conditions.