On February 27, 2020 Novocure (NASDAQ: NVCR) reported financial results for the quarter and year ended December 31, 2019, highlighting continued commercial execution, strengthening financial performance and clinical and product development programs intended to unlock future value (Press release, NovoCure, FEB 27, 2020, View Source [SID1234554925]). Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer by developing and commercializing its innovative therapy, Tumor Treating Fields.

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Fourth quarter and full year 2019 highlights include:

(1) An "active patient" is a patient who is receiving treatment under a commercial prescription order as of the measurement date, including patients who may be on a temporary break from treatment and who plan to resume treatment in less than 60 days.

(2) A "prescription received" is a commercial order for Optune or NovoTTF-100L that is received from a physician certified to treat patients for a patient not previously on Optune or NovoTTF-100L. Orders to renew or extend treatment are not included in this total.

"We start 2020 with substantial momentum from an exceptional 2019," said Asaf Danziger, Novocure’s Chief Executive Officer, "In 2019, we generated $351 million in net revenues and added over $80 million in cash on hand to our balance sheet. The financial strength derived from our existing indications allows us to fund significant investments in clinical and product innovation to advance our proprietary cancer therapy platform. Our focus on strengthening our foundation and executing our strategic plan to deliver value to our patients, employees, and shareholders is unwavering."

"In 20 years of preclinical research across a wide variety of tumor cell lines and cancer models, Tumor Treating Fields has demonstrated a consistent anti-mitotic effect. We are enrolling patients in six clinical programs, including four randomized, phase 3 pivotal trials, and are very optimistic about the potential application of Tumor Treating Fields beyond our currently approved indications," continued William Doyle, Novocure’s Executive Chairman. "Also, new research is pointing the way to further improving the efficacy of the Tumor Treating Fields platform, and we are advancing multiple product development programs to this end. We are excited about the potential to significantly improve patient outcomes as we work to extend survival in some of the most aggressive forms of cancer."

Fourth quarter 2019 operating statistics and financial update

For the quarter ended December 31, 2019, net revenues were $99.2 million, representing 42% growth compared to the fourth quarter 2018.

In the United States, net revenues totaled $65.9 million in the quarter ended December 31, 2019, representing 49% growth compared to the same period in 2018.
In Germany and other EMEA markets, net revenues totaled $25.8 million in the quarter ended December 31, 2019, representing 14% growth compared to the same period in 2018.
In Japan, net revenues totaled $5.6 million in the quarter ended December 31, 2019, representing 95% growth compared to the same period in 2018.
In Greater China, net revenues totaled $1.9 million in the quarter ended December 31, 2019, representing 138% growth compared to the same period in 2018.
There were 2,909 active patients at December 31, 2019, representing 22% growth compared to December 31, 2018, and six percent growth compared to September 30, 2019.

In the United States, there were 1,952 active patients at December 31, 2019, representing 19% growth compared to December 31, 2018.
In Germany and other EMEA markets, there were 765 active patients at December 31, 2019, representing 17% growth compared to December 31, 2018.
In Japan, there were 192 active patients at December 31, 2019, representing 109% growth compared to December 31, 2018.
Additionally, 1,380 prescriptions were received in the quarter ended December 31, 2019, representing five percent growth compared to the same period in 2018, and five percent growth compared to the quarter ended September 30, 2019. In the quarter ended December 31, 2019, 1,079 Optune prescriptions were written for patients with newly diagnosed glioblastoma.

In the United States, 1,002 prescriptions were received in the quarter ended December 31, 2019, representing six percent growth compared to the same period in 2018.
In Germany and other EMEA markets, 285 prescriptions were received in the quarter ended December 31, 2019, representing an 11% decrease compared to the same period in 2018.
In Japan, 93 prescriptions were received in the quarter ended December 31, 2019, representing 79% growth compared to the same period in 2018.
For the three months ended December 31, 2019, cost of revenues was $24.8 million compared to $23.0 million for the same period in 2018, representing an increase of 8%. The increase was primarily due to the cost of shipping transducer arrays to a higher volume of commercial patients. Gross margin was 75% for the three months ended December 31, 2019 and 67% for the three months ended December 31, 2018.

Research, development and clinical trials expenses for the three months ended December 31, 2019, were $23.7 million compared to $15.0 million for the same period in 2018, representing an increase of 58%. This was primarily due to an increase in clinical development expenses driven by our ongoing phase 3 pivotal trials and an increase in costs associated with product development and medical affairs.

Sales and marketing expenses for the three months ended December 31, 2019, were $26.8 million compared to $21.2 million for the same period in 2018, representing an increase of 26%. This was primarily due to increased marketing expenses related to the launch of NovoTTF-100L and an increase in personnel costs to support our growing commercial business.

General and administrative expenses for the three months ended December 31, 2019 were $23.8 million compared to $19.1 million for the same period in 2018, representing an increase of 25%. This was primarily due to an increase in personnel costs and an increase in professional services.

Net income for the three months ended December 31, 2019, was $4.3 million compared to net loss of $15.6 million for the same period in 2018.

At December 31, 2019, we had $177.3 million in cash and cash equivalents and $148.8 million in short-term investments, for a total balance of $326.1 million in cash, cash equivalents and short-term investments. This represents an increase of $13.5 million in cash and investments since September 30, 2019.

Fourth quarter 2019 non-U.S. GAAP measures

We also measure our performance based upon a non-U.S. GAAP measurement of earnings before interest, taxes, depreciation, amortization and shared-based compensation ("Adjusted EBITDA"). We believe Adjusted EBITDA is useful to investors in evaluating our operating performance because it helps investors evaluate and compare the results of our operations from period to period by removing the impact of earnings attributable to our capital structure, tax rate and material non-cash items, specifically share-based compensation.

Adjusted EBITDA increased by $13.1 million, or 314%, to $17.3 million for the three months ended December 31, 2019 from $4.2 million for the three months ended December 31, 2018. This improvement in fundamental financial performance was driven by top-line growth and disciplined execution.

Anticipated clinical milestones

Interim analysis of phase 3 pivotal LUNAR trial in non-small cell lung cancer (H2 2020)
Data from phase 2 pilot HEPANOVA trial in advanced liver cancer (2021)
Data from phase 3 pivotal METIS trial in brain metastases (2021)
Interim analysis of phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer (2021)
Final data from phase 3 pivotal LUNAR trial in non-small cell lung cancer (2022)
Interim analysis of phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer (2022)
Final data from phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer (2022)
Final data from phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer (2024)
Conference call details

Novocure will host a conference call and webcast to discuss fourth quarter and full year 2019 financial results at 8 a.m. EST today, Thursday, February 27, 2020. Analysts and investors can participate in the conference call by dialing 855-442-6895 for domestic callers and 509-960-9037 for international callers, using the conference ID 1769503.

The webcast, earnings slides presented during the webcast and the corporate presentation can be accessed live from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for at least 14 days following the call. Novocure has used, and intends to continue to use, its investor relations website, as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

On February 27, 2020 Cryoport, Inc. (NASDAQ: CYRX) (NASDAQ: CYRXW) ("Cryoport" or the "Company"), a global leader in life sciences solutions, reported that the Company will report financial results for the fourth quarter and fiscal year ended December 31, 2019 on Thursday, March 5, 2020 after U.S. markets close (Press release, Cryoport, FEB 27, 2020, View Source [SID1234554942]).

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In addition to the earnings release, a document titled "Cryoport 2019 Year in Review", which will provide a review of Cryoport’s recent financial and operational performance and a general business update, will be issued by management at 4:05 pm ET on Thursday, March 5, 2020. The document is designed to be read by investors before the questions and answers conference call and can be accessed at http://ir.cryoport.com/events-and-presentations.

Cryoport management will host a conference call at 5:00 pm ET on March 5, 2020. The conference call will be in the format of a questions and answers session and will address any queries investors have regarding the Company’s reported results.

Conference Call Information

Date:

March 5, 2020

Time:

5:00 p.m. ET

Dial-in numbers:

+1 (855) 327-6837 (U.S.), +1 (631) 891-4304 (International)

Confirmation code:

Request the "Cryoport Call"

Live webcast:

‘Investor Relations’ section at www.cryoport.com or at this link. Please allow 10 minutes prior to the call to visit this site to download and install any necessary audio software.

An archive of the question and answer webcast will be available approximately three hours after completion of the live event and will be accessible on the Investor Relations section of the Company’s website at www.cryoport.com for a limited time. To access the replay of the webcast, please follow this link. A dial-in replay of the call will also be available to those interested until March 12, 2020. To access the replay, dial +1 (844) 512-2921 (United States) or +1 (412) 317-6671 (International) and enter replay pin number: 10008682.

On February 27, 2020, Deka Biosciences reported that an upcoming episode of Advancements with Ted Danson, scheduled to broadcast 2Q/2020, will explore innovative treatment solutions for maladies, such as Inflammatory Bowel Disease (IBD), specifically Crohn’s Disease (Crohn’s), and Oncology (Press release, Deka Biosciences, FEB 27, 2020, View Source [SID1234580080]). Check local listings for more info.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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This segment will focus on a novel platform developed by Deka Biosciences, Inc. (Deka Biosciences), that will enable the delivery of next generation cytokine or combination of cytokines to a specific tissue of interest. Viewers will learn how this cutting-edge technology, termed Diakines, has led to the development of two potential therapeutic molecules involving an affinity modified Interleukin 10 cytokine.

The show will also explore how Deka Biosciences is using Diakines to harness the spectrum of therapeutically useful and clinically validated IL10 and other cytokine specific biologies. Spectators will see how these Diakines can maximize patient benefits through improved PK/PD function combined with a MOA directed patient selection strategy.

"The biopharma industry has known for a while that cytokines play an integral role in immunology and disease management, and that delivery of cytokine therapeutics into diseased tissues will dramatically enhance therapeutic benefit," said Dr. John Mumm, co-founder & CEO of Deka Biosciences. He continued to say, "Deka Biosciences has harnessed the wealth of clinical knowledge around cytokines and IL-10 in particular, to develop a novel delivery platform to enrich cytokine variants in effected tissues, coupled with methods to determine how to select the patients with the greatest likelihood of response to ensure that the right patients get the right medicines."

In addition, the show will also inform about Deka Biosciences’ Precision Medicine strategy, which enables Deka to identify the right patients to treat with these new medicines.

"Deka’s platform has the potential to enable discoveries of next generation therapies," said Richard Lubin, senior producer for DMG Productions and the Advancements series. "We are eager to explore how Deka is set to influence future treatment options for IBD, Crohn’s."

On February 27, 2020 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported financial results for the fourth quarter and year ended December 31, 2019 and provided a corporate update (Press release, Jounce Therapeutics, FEB 27, 2020, View Source [SID1234554864]).

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"On the heels of a year of significant clinical progress in 2019, we have set the pace for a robust 2020 with the advancement of our vopratelimab Phase 2 studies, the ongoing EMERGE trial and the upcoming SELECT trial. The recent announcement of the TISvopra biomarker for patient selection in SELECT is a testament to our Translational Science Platform and further emphasizes our vision of bringing the right immunotherapy to the right patients," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "With two of our programs, vopratelimab and JTX-4014, in clinical trials, along with the advancement of our potential first-in-class monoclonal antibody, JTX-1811, into IND enabling activities, we are continuing to establish our differentiated approach to immunotherapy and clinical trial design. We look forward to executing on several key milestones in 2020 across our growing pipeline."

Pipeline Update and Highlights:
Vopratelimab

Established two development paths for vopratelimab program: In early 2019, Jounce announced two development paths for vopratelimab, which are now represented by two distinct and independent Phase 2 clinical trials, EMERGE and SELECT. Both trials are based on the biology related to the pharmacodynamic biomarker, ICOS hi CD4 T cells, which emerge in the blood of patients due to vopratelimab and not PD-1 inhibitors and are associated with clinical benefit.
— Enrollment on track in Phase 2 EMERGE trial: EMERGE trial enrollment in non-small cell lung cancer (NSCLC) remains on track, and Jounce expects to report preliminary efficacy and related biomarker data in the second half of 2020.
— Identified the baseline TISvopra biomarker: In February 2020, Jounce presented new data announcing the identification of the predictive biomarker associated with vopratelimab patient selection, known as TISvopra, which will be used in the upcoming SELECT trial to select patients more likely to develop ICOS hi CD4 T cells and experience clinical benefit in the presence of vopratelimab. The TISvopra biomarker is a baseline RNA signature with a threshold optimized for the prediction of the emergence of ICOS hi CD4 T cells and is expected to predict for both vopratelimab and PD-1 activity.
— Announced trial design for upcoming Phase 2 SELECT trial: In January 2020, Jounce announced the trial design for SELECT, a randomized, ex-U.S. trial that will evaluate vopratelimab and JTX-4014, a PD-1 inhibitor, in patients with second line, PD-1 inhibitor naive NSCLC. Jounce expects to enroll approximately 75 patients, who will be selected using the TISvopra biomarker. Jounce expects to initiate the Phase 2 SELECT trial in mid-2020 and report interim clinical data in 2021.
JTX-4014

Established JTX-4014 as combination agent for Phase 2 SELECT trial: Based on the results of the Phase 1 JTX-4014 trial announced in November 2019, Jounce plans to use JTX-4014 as the PD-1 inhibitor in combination with its other product candidates beginning with the upcoming Phase 2 SELECT trial.
Presented safety and preliminary efficacy data from Phase 1 trial at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting: In November 2019, Jounce presented safety and preliminary efficacy data from the Phase 1 trial of JTX-4014 at SITC (Free SITC Whitepaper) demonstrating anti-tumor activity with an overall RECIST 1.1 response rate of 16.7% (3/18), one complete response, two partial responses and a disease control rate of 44.4% (8/18) in patients with advanced refractory solid tumor malignancies and an average of over four lines of prior therapies. JTX-4014 was found to have an acceptable safety profile in this trial.
JTX-1811

Named JTX-1811 as next development candidate from Translational Science Platform: In December 2019, JTX-1811 was selected as the next development candidate to emerge from Jounce’s Translational Science Platform. JTX-1811 is a monoclonal antibody designed to selectively deplete immuno-suppressive T regulatory cells. Jounce will present additional preclinical data at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting and expects to file an Investigational New Drug (IND) application in the first half of 2021.
Research Collaborations and Partnerships:

Established research collaboration with NanoString Technologies to support the application of TISvopra in Phase 2 SELECT trial: In January 2020, Jounce entered into a new research collaboration with NanoString Technologies for the application of the TISvopra biomarker, including the optimized selection threshold in the SELECT trial. The TISvopra clinical trial assay will be implemented on the nCounter Dx Analysis System.
Updated strategic collaboration with Celgene Corporation: In July 2019, Jounce and Celgene entered into a mutual agreement to terminate their broad strategic collaboration established in 2016. As a result, Jounce owns all global rights to its current pipeline, including vopratelimab, JTX-4014, JTX-1811 and all discovery-stage assets. Separately, Celgene obtained exclusive worldwide licensing rights to JTX-8064, a potential first-in-class antibody that targets the LILRB2 receptor on macrophages. Under the terms of the new license agreement, Jounce received a $50.0 million non-refundable license fee and is eligible to receive up to $480.0 million from Celgene in development, regulatory and commercial milestone payments, as well as royalties from potential worldwide sales.
Fourth Quarter and Full Year 2019 Financial Results:

Cash position: As of December 31, 2019, cash, cash equivalents and investments were $170.4 million, compared to $195.9 million as of December 31, 2018. The decrease in cash, cash equivalents and investments was primarily due to operating costs incurred during the year, offset by the $50.0 million license fee received in July 2019 pursuant to Jounce’s JTX-8064 license agreement with Celgene.
License and collaboration revenue: No license and collaboration revenue was recognized during the fourth quarter of 2019, compared to $20.1 million for the same period in 2018. License and collaboration revenue was $147.9 million for the full year 2019, compared to $65.2 million for the full year 2018. License and collaboration revenue recognized during 2019 was comprised of $50.0 million of cash revenue related to Jounce’s JTX-8064 license agreement with Celgene and $97.9 million of non-cash revenue recognition relating to the $225.0 million upfront payment received from Celgene in July 2016. License and collaboration revenue recognized during 2018 was comprised solely of non-cash revenue recognition related to the July 2016 upfront payment.
Research and development expenses: Research and development expenses were $16.6 million for both the fourth quarter of 2019 and 2018. Research and development expenses were $67.1 million for the full year 2019, compared to $70.1 million for the full year 2018. The decrease in research and development expenses for the full year 2019 was primarily due to $6.0 million of decreased manufacturing and IND-enabling expenses as well as $0.9 million of decreased lab consumable costs. These decreases were partially offset by $3.1 million of increased employee compensation costs.
General and administrative expenses: General and administrative expenses were $6.9 million for the fourth quarter of 2019, compared to $6.6 million for the same period in 2018 and $27.9 million for the full year 2019, compared to $26.4 million for the full year 2018. The increase in general and administrative expenses for both the fourth quarter of 2019 and the full year 2019 was primarily attributable to increased employee compensation costs.
Net (loss) income: Net loss was $22.7 million for the fourth quarter of 2019, or a basic and diluted net loss per share of $0.68. Net loss was $2.0 million for the same period in 2018, or a basic and diluted net loss per share of $0.06. Net income was $56.8 million for the full year 2019, resulting in basic net income per share of $1.72 and diluted net income per share of $1.66. Net loss was $27.4 million for the full year 2018, or a basic and diluted net loss per share of $0.84. Net income recognized for the full year 2019 was primarily attributable to $147.9 million of license and collaboration revenue recognized under Jounce’s agreements with Celgene.
Financial Guidance:
Based on its current operating and development plans, Jounce expects gross cash burn on operating expenses and capital expenditures for the full year 2020 to be approximately $80.0 million to $95.0 million. Jounce will no longer provide license and collaboration revenue guidance as potential future payments under the JTX-8064 license agreement with Celgene are royalty- and milestone-based.

Given the strength of its balance sheet, Jounce expects its existing cash, cash equivalents and investments to be sufficient to enable the funding of its operating expenses and capital expenditure requirements through the end of 2021.

Conference Call and Webcast Information:
Jounce Therapeutics will host a live conference call and webcast today at 8:00 a.m. ET. To access the conference call, please dial (866) 916-3380 (domestic) or (210) 874-7772 (international) and refer to conference ID 7889239. The live webcast can be accessed under "Events & Presentations" in the Investors and Media section of Jounce’s website at www.jouncetx.com. The webcast will be archived and made available for replay on Jounce’s website approximately two hours after the call and will be available for 30 days.

On February 27, 2020 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for rare and ultra-rare diseases, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions using the latest biotechnology, reported that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for Crysvita (burosumab) for the treatment of FGF23-related hypophosphatemia associated with phosphaturic mesenchymal tumors (tumor-induced osteomalacia; TIO) that cannot be curatively resected or localized (Press release, Kyowa Hakko Kirin, FEB 27, 2020, View Source [SID1234554891]). The FDA has assigned priority review designation with a Prescription Drug User Fee Act (PDUFA) target date of June 18, 2020.

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"We appreciate the FDA’s collaboration in evaluating the data, and as a result, we are another step closer to bringing the first treatment to patients with this devastating disease in the setting of an unresectable tumor," said Camille L. Bedrosian, M.D., Chief Medical Officer of Ultragenyx. "We look forward to continuing to work closely with the FDA with the goal of bringing Crysvita to patients with TIO as quickly as possible."

"The discovery and submission of Crysvita has meant a great deal to patients and families that previously had no other treatment options," said Tomohiro Sudo, Head of Global Product Management Office of Kyowa Kirin. " "If approved, we believe Crysvita may also become a meaningful treatment option for many patients with TIO in the U.S."

The sBLA package includes data from two single-arm Phase 2 studies, a 144-week study in 14 adult patients conducted by Ultragenyx in the U.S. and an 88-week study in 13 adult patients conducted by Kyowa Kirin in Japan and South Korea.

Crysvita is approved by the U.S. FDA for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients six months of age and older, and by Health Canada and Brazil’s National Health Surveillance Agency (ANVISA) for the treatment of XLH in adult and pediatric patients one year of age and older. In Japan, it is approved by the Ministry of Health, Labor and Welfare (MHLW) for the treatment of FGF23-related hypophosphatemic rickets and osteomalacia. In Europe, Crysvita has received European conditional marketing authorization for the treatment of XLH with radiographic evidence of bone disease in children 1 year of age and older and adolescents with growing skeletons, and an application for the expanded use in adults with XLH is currently under review by the European Medicines Agency.

See below for Important Safety Information for Crysvita in X-linked hypophosphatemia.

About Tumor-Induced Osteomalacia (TIO)
TIO is caused by typically benign tumors that produce excess levels of fibroblast growth factor 23 (FGF23), causing phosphate wasting in the urine that leads to severe hypophosphatemia, osteomalacia, muscle weakness, fatigue, bone pain and fractures. The symptoms rapidly resolve if the causal tumors or lesion can be resected; however, there are cases in which resection is not feasible or recurrence of the tumor occurs after resection. In patients for whom the tumor or lesion is inoperable, the current treatment consists of oral phosphate and/or vitamin D replacement. Efficacy of this management is often limited, as it does not treat the underlying disease and its benefits must be balanced with monitoring for potential risks such as nephrocalcinosis, hypercalciuria and hyperparathyroidism. An estimated 500-1,000 people in the United States have TIO, and approximately half of all cases are inoperable.

About Crysvita
Crysvita (burosumab-twza) is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Kirin, against the phosphaturic hormone FGF23. FGF23 is a hormone that reduces serum levels of phosphorus and active vitamin D by regulating phosphate excretion and active vitamin D production by the kidney. Phosphate wasting in TIO and other hypophosphatemic conditions, including XLH, is caused by excessive levels and activity of FGF23. Crysvita is designed to bind to and thereby inhibit the biological activity of FGF23. By blocking excess FGF23 in patients with TIO and XLH, Crysvita is intended to increase phosphate reabsorption from the kidney and increase the production of vitamin D, which enhances intestinal absorption of phosphate and calcium.

Kyowa Kirin and Ultragenyx have been collaborating in the development and commercialization of Crysvita globally based on the collaboration and license agreement between the parties.

INDICATION (IN THE U.S.)

Crysvita is indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.

IMPORTANT SAFETY INFORMATION Crysvita should not be taken if:

• An oral phosphate supplement and/or a specific form of vitamin D supplement are taken (such as calcitriol, paricalcitol, doxercalciferol, calcifediol).

• Phosphorus levels from a blood sample are within or above the normal range for age.

• Kidney problems are present. What is the most important information to know about Crysvita?

• Some patients developed allergic reactions (rash and hives) while taking Crysvita. Doctors will monitor for symptoms of an allergic reaction while Crysvita is taken.

• High levels of phosphorus in the blood have been reported in some patients taking Crysvita. This may be related to a risk of high calcium levels in the kidneys. Doctors will collect samples to monitor levels.

• Administration of Crysvita may result in reactions at the injection site, such as hives, reddening of the skin, rash, swelling, bruising, pain, severe itching of the skin, and collection of blood outside of a blood vessel (hematoma). What are the possible side effects of Crysvita?

• The most common adverse reactions that were seen in children with XLH are: o Fever o Injection site reaction o Cough o Vomiting o Pain in arms and legs o Headache o Tooth infection o Dental cavities o Diarrhea o Decreased vitamin D levels o Toothache o Constipation o Muscle pain o Rash o Dizziness o Nausea

• The most common adverse reactions that were seen in adults with XLH are: o Back pain o Headache o Tooth infection o Restless leg syndrome o Decreased vitamin D levels o Dizziness o Muscle spasms o Constipation o Phosphorus levels increased in the blood

• Narrowing of the spaces within the spine is common in adults with XLH and pressure on the spinal cord has been reported in adults taking Crysvita. It is not known if taking Crysvita worsens the narrowing of the spaces within the spine or the pressure on the spinal cord. Before taking Crysvita, doctors should be informed about all medications (including supplements) and medical conditions, including if:

• One is taking oral phosphate and/or active vitamin D (such as calcitriol, paricalcitol, doxercalciferol, calcifediol).

• One is pregnant, thinks she may be pregnant, or plans to become pregnant. There is not enough experience to know if Crysvita may harm an unborn baby. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-888-756-8657.

• One is breastfeeding or plans to breastfeed. There is not enough experience to know if Crysvita passes into breast milk. Women should talk with their doctors about the best way to feed their babies while taking Crysvita. While taking Crysvita, doctors should be informed if one experiences:

• An allergic reaction such as rash or hives

• A rash, swelling, bruising or other reaction at the injection site

• New or worsening restless leg syndrome

These are not all the possible side effects of Crysvita. Doctors should be contacted for medical advice about side effects.

Side effects may be reported to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.

Side effects may also be reported to Kyowa Kirin, Inc. at 1-888-756-8657.

Please see full Prescribing Information for additional Important Safety Information.