On February 26, 2020 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the fourth quarter and full year 2019 (Press release, BioMarin, FEB 26, 2020, View Source [SID1234554801]).

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Total Net Product Revenues for the fourth quarter of 2019 increased to $436.6 million, compared to $347.2 million for the fourth quarter of 2018. The increase in Net Product Revenues was attributed to the following:
•Palynziq Net Product Revenues increased by $23.6 million, driven by a combination of revenue from patients achieving maintenance dosing and new patients initiating therapy. In the U.S. Palynziq received approval from the U.S. Food and Drug Administration (FDA) in May 2018 and launched in the third quarter of that year. Palynziq received approval in May 2019 from the European Commission (EC) and commercial sales in Europe commenced in the fourth quarter of 2019;
•Vimizim Net Product Revenues increased by $18.3 million, or 16%, driven primarily by patient growth in the U.S. and orders from Brazil;
•Naglazyme Net Product Revenues increased by $18.1 million, or 24%, primarily due to orders from Brazil;
•Brineura Net Product Revenues increased by $13.0 million, or 107%, due in large part by patient growth across all regions particularly Europe;
•Kuvan Net Product Revenues increased by $10.4 million, or 9%, primarily driven by an increase in patients in North America; and
•Aldurazyme Net Product Revenues increased $6.5 million, or 37%, due to higher sales volume to Sanofi Genzyme.
The increase in GAAP Net Income for the fourth quarter of 2019, compared to GAAP Net Loss for the same period in 2018 was primarily due to the following:
•increased gross profits of $80.3 million primarily driven by increased product sales; partially offset by
•higher selling, general and administrative (SG&A) expense related to pre-commercialization activities for valoctocogene roxaparvovec, and support of the EU commercial launch and continued U.S. expansion of Palynziq.
Non-GAAP Income for the fourth quarter of 2019 increased to $46.4 million, compared to Non-GAAP Loss of $10.9 million for the same period in 2018. The increase in Non-GAAP Income for the quarter, compared to the same period in 2018, was attributed to higher gross profit and decreased research and development expense, partially offset by higher SG&A expense.

As of December 31, 2019, BioMarin had cash, cash equivalents and investments totaling approximately $1.2 billion, as compared to $1.3 billion on December 31, 2018.
Commenting on 2019 results, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, said, "Our performance in 2019 reflects the clinical, regulatory and financial goals we set for ourselves a year ago. We completed enrollment of the Phase 3 Interim Analysis cohort with valoctocogene roxaparvovec and met the criteria for expedited review of marketing applications in the United States and Europe. With those applications now under review by global health authorities, we await the potential approval of valoctocogene roxaparvovec, the first gene therapy product to be reviewed for the treatment of severe hemophilia A. Another significant success in 2019 was the completion of and results from our global Phase 3 study with vosoritide for achondroplasia. With a high degree of statistical significance (p<0.0001) the primary endpoint of increase in growth velocity from baseline over a one year period was demonstrated with vosoritide. Based on these results, the Company plans to meet with health authorities in the first half of 2020 to discuss plans for submitting marketing applications later this year. Another study with

vosoritide, the global Phase 2 in infants and young children (less than 60 months old), is continuing enrollment. All subjects from ages 6 months through 5 years are almost completely enrolled. The youngest cohort, infants up to 6 months old, is actively enrolling. Interest in this study with very young children has been extremely robust, demonstrating that families are keen to seek treatment for their children as early as possible."
Mr. Bienaimé continued, "In addition to these later-stage regulatory and clinical milestones in 2019, we made significant progress advancing our early-stage pipeline. Building on the success of our phenylketonuria (PKU) franchise with Palynziq and Kuvan, we announced in January that both the United States and the United Kingdom health authorities had given the go-ahead to start dosing patients with PKU with our BMN 307 gene therapy in a Phase 1/2 study. We plan to treat patients with BMN 307 in the first quarter using product made at commercial scale from our award-winning gene therapy manufacturing facility. Other additions to the pipeline announced at R&D Day last November included, BMN 331 gene therapy for hereditary angioedema and vosoritide for dominantly inherited short stature. Finally, our most recently approved product, Palynziq for the treatment of PKU, continues along a very strong growth trajectory since approval in 2018 in the U.S. We have been very pleased with the pace of the U.S. launch, as we ended 2019 with 762 patients on reimbursed Palynziq, and an additional 143 naïve patients having completed enrollment and awaiting their first injection. Based on the tremendous interest in treatment with Palynziq, we provided full-year guidance for Palynziq Net Product Revenues of between $180 million to $210 million for full-year 2020, representing significant growth over 2019. Our revenue growth and improvement in profitability also increased our operating cash flows, as shown by the growth of our total cash and investments for the second straight quarter. Having achieved all of our key clinical, regulatory and financial goals in 2019, 2020 looks poised to be one of our most significant value-creating years to date."

(1) 2020 GAAP Net Income guidance does not reflect the potential impact on non-cash GAAP income tax associated with the tax effects of potential intra-entity intangible asset transfers between BioMarin entities as a result of changing international tax laws. Any such changes, if implemented, are not expected to have an impact on operations or cash flows in 2020 but may have an impact on GAAP Net Income in the form of an income tax benefit of potentially greater than $500 million.

(2) All Financial Guidance items are calculated based on U.S. GAAP with the exception of Non-GAAP Income/Loss. Refer to Non-GAAP Information beginning on page 10 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the corresponding GAAP reported information.
Key Program Highlights
•Valoctocogene roxaparvovec gene therapy for severe hemophilia A: On February 20, 2020, FDA accepted for Priority Review the Biologics License Application (BLA) for valoctocogene roxaparvovec. The Prescription Drug User Fee Act (PDUFA), or target action date for the BLA, has been set for August 21, 2020. On December 23, 2019, the Company announced that the European Medicines Agency (EMA) validated the Company’s Marketing Authorization Application (MAA) for valoctocogene roxaparvovec which has been in

review under accelerated assessment since January. The submissions are based on the Phase 3 interim analysis and the updated three-year Phase 1/2 data of patients treated with valoctocogene roxaparvovec. Both submissions represent the first time a gene therapy product for any type of hemophilia indication is under review for marketing authorization by health authorities.

BioMarin has dosed 134 study participants in the full GENEr8-1 Phase 3 study with 52-week results expected in the first quarter of 2021. Although the trial is open label, BioMarin has implemented a data access plan designed to substantially mirror a blinded trial. This restricts the release of any ongoing data to a small group of medical personnel monitoring and managing the trial, and then, only to the extent necessary to perform their monitoring responsibilities.

BioMarin intends to provide a 4 year update with the 6e13 vg/kg dose subjects and a 3 year update with the 4e13 vg/kg dose subjects from the ongoing Phase 2 study in mid-2020.
•Palynziq for PKU: Palynziq, an injection to reduce blood phenylalanine (Phe) concentrations in adult patients with PKU, was added to BioMarin’s commercial product portfolio upon its U.S. approval May 2018. As of December 31, 2019, 762 patients were on reimbursed Palynziq, with an additional 143 naïve patients enrolled and awaiting their first treatment with commercial Palynziq. Of the 762 patients on therapy at the end of the fourth quarter, 625 were formerly naïve patients and 137 had transitioned from clinical studies. 143 enrolled naive patients were awaiting their first administration of Palynziq as of the end of the fourth quarter. Of the 125 PKU clinics in the U.S., 97 sites had active patients currently on therapy as of December 31, 2019.

On May 6, 2019, the EC granted marketing authorization for Palynziq at doses of up to 60 milligrams once daily, to reduce blood Phe concentrations in patients with PKU aged 16 and older, who have inadequate blood Phe control (blood Phe levels greater than 600 micromol/L) despite prior management with available treatment options. The Company is in the process of securing reimbursement on a country-by-country basis across the European Union and anticipates meaningful revenue contributions from this region in 2020.

•Vosoritide for children with achondroplasia: On December 16, 2019, the Company reported positive final results from its randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of vosoritide. The placebo-adjusted increased change from baseline in growth velocity after one year of treatment with vosoritide, the primary endpoint, was 1.6 cm/yr (p<0.0001). Vosoritide is an investigational, once daily injection analog of C-type Natriuretic Peptide (CNP). The study enrolled 121 children aged 5 to 14 with achondroplasia, the most common form of disproportionate short stature. The results were consistent across the broad patient population studied. Vosoritide was generally well tolerated with no clinically significant blood pressure decreases. Based on these results, the Company plans to meet with health authorities in the first half of 2020 to discuss plans for submitting marketing applications later this year.

On November 14, 2019, the Company provided an update on the ongoing Phase 2 study of vosoritide which demonstrated over 54 months that children in cohort 3 (N=10) of the study, at a dose of 15 µg/kg/day, achieved a statistically significant (p< 0.005) cumulative mean additional height gain of 9.0 cm compared to children, matched for age and gender, in a new comprehensive natural history achondroplasia dataset (N=619). 2.2 cm of this additional increase occurred in the last 12 months further informing our understanding of vosoritide’s ongoing treatment impact. These data are expected to corroborate maintenance of effect at the time of anticipated marketing application submissions later this year.

The vosoritide development program includes four distinct areas of focus to support global approval. In addition to the completed Phase 3 study and ongoing Phase 2 study in children ages 5-14 years, the global program includes a large contemporaneous natural history study which is underway.
The fourth component of the Company’s global development program with vosoritide, includes a large Phase 2 study in infants and young children (newborn to 60 months old) with achondroplasia, to determine the impact of treatment in this age group. Cohorts 1 and 2 include children from ages 6 months through 5 years of age, is near enrollment completion. Cohort 3, includes children ages 0 to 6 months old and, is actively enrolling.
•BMN 307 gene therapy product candidate for phenylketonuria (PKU): On January 13, 2020 the Company announced that both the FDA and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the

U.K. have granted the Company Investigational New Drug (IND) status and approved its Clinical Trial Application (CTA), respectively, for BMN 307.

The Company expects to start dosing patients in PHEARLESS, a Phase 1/2 study, in the first quarter of 2020 with product made at commercial scale from its award-winning gene therapy manufacturing facility. Both the FDA and EMA have granted BMN 307 Orphan Status.
Preclinical data with BMN 307 demonstrated a lifetime Phe correction sustained at 80 weeks in mouse models. BMN 307 is an AAV vector containing the DNA sequence that codes for the phenylalanine hydroxylase enzyme that is deficient in people with PKU.

•BMN 331 gene therapy product candidate for Hereditary Angioedema (HAE): On November 14, 2019, the Company introduced its third gene therapy candidate, BMN 331, for the treatment of Hereditary Angioedema (HAE). BioMarin plans to build on its ever wider and deeper experience in developing gene therapies for severe hemophilia A and PKU to improve efficiencies in the development process, and optimize capsid and transgene design. The Company expects to begin IND-enabling studies in early to mid-2020.

•Vosoritide for the treatment of Dominantly Inherited Short Stature (DISS): On November 14, 2019, the Company announced that vosoritide will be studied in broader genetic statural abnormalities starting with dominantly inherited short stature (DISS), as part of a research collaboration with Children’s National Hospital. The Company plans to build on its learnings with vosoritide in achondroplasia and look for efficiencies in the development process, particularly around pre-clinical research and manufacturing. The Company expects the trial with vosoritide for DISS to begin mid-2020.

•Gene Therapy manufacturing productivity increases capacity: On January 13, 2020, the Company announced that significant improvements in productivity in the gene therapy facility had increased capacity for up to 10,000 patients per year, depending on dose and product mix.
BioMarin will host a conference call and webcast to discuss fourth quarter and full year 2019 financial results and 2020 guidance today, Wednesday, February 26, 2020 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.
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Conference ID: 9967337
Conference ID: 9967337