Expanded Indication in the U.S. Now Includes Children of all ages with Achondroplasia

美国的扩大适应症现在包括所有年龄段的软骨发育不全的儿童

SAN RAFAEL, Calif., Oct. 20, 2023 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN), a global biotechnology company dedicated to transforming lives through genetic discovery, today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for VOXZOGO® (vosoritide) to increase linear growth in pediatric patients with achondroplasia with open epiphyses (growth plates).

加利福尼亚州圣拉斐尔，2023年10月20日/PRNewswire/-BioMarin Pharmaceutical Inc.（纳斯达克股票代码：BMRN），一家致力于通过基因发现改变生活的全球生物技术公司，今天宣布，美国食品和药物管理局（FDA）已批准VOXZOGO®（vosoritide）的补充新药申请（sNDA），以增加患有开放性骨骺（生长板）的软骨发育不全的儿科患者的线性生长。

This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Previously, VOXZOGO was indicated for children who were 5 years of age and older. This expanded indication now includes children of all ages with open growth plates..

基于年度增长速度的提高，该指示在加速批准下获得批准。以前，VOXZOGO适用于5岁及以上的儿童。现在，这种扩展的适应症包括开放式生长板的所有年龄段的儿童。。

'We are pleased that VOXZOGO is now available for children of all ages with achondroplasia,' said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. 'We are grateful for the collaboration of the achondroplasia community, physicians, and the children and their families who have played a crucial role in advancing this clinical program.

“我们很高兴VOXZOGO现在适用于所有年龄段软骨发育不全的儿童，”BioMarin全球研究与开发总裁Hank Fuchs说我们感谢软骨发育不全社区，医生以及在推进这一临床计划中发挥关键作用的儿童及其家人的合作。

We also look forward to further understanding the potential role of VOXZOGO in other genetic short stature conditions, including hypochondroplasia.'.

我们还期待进一步了解VOXZOGO在其他遗传性矮小状况（包括软骨发育不良）中的潜在作用。

'VOXZOGO is the only approved treatment for children with achondroplasia. Until now, it has only been approved in the U.S. for children aged 5 and older with open growth plates,' said William Wilcox, M.D., professor of human genetics at Emory University. 'I am delighted that VOXZOGO is now approved for younger children where we hope to have potentially greater impact by starting treatment earlier and, as a result, a much longer treatment window.'.

'VOXZOGO是唯一批准用于软骨发育不全儿童的治疗方法。埃默里大学人类遗传学教授威廉·威尔科克斯（William Wilcox）博士说，到目前为止，它只在美国被批准用于5岁及以上开放生长板的儿童我很高兴VOXZOGO现在被批准用于年幼的儿童，我们希望通过尽早开始治疗并因此延长治疗时间来产生更大的影响。

BioMarin conducted a randomized, double-blind, placebo-controlled Phase 2 clinical trial evaluating the safety and efficacy of VOXZOGO in children aged 5 and under (Study 111-206). Based on the results of this trial, together with evidence from the adequate and well controlled Phase 3 study in pediatric patients aged 5 years and older (Study 111-301), safety and effectiveness of VOXZOGO have been established in pediatric patients of all ages for the improvement in linear growth in children with achondroplasia with open epiphyses.

BioMarin进行了一项随机，双盲，安慰剂对照的2期临床试验，评估了VOXZOGO在5岁及以下儿童中的安全性和有效性（研究111-206）。根据这项试验的结果，以及来自5岁及以上儿科患者（研究111-301）的充分和良好控制的3期研究的证据，已经在所有年龄段的儿科患者中建立了VOXZOGO的安全性和有效性用于改善开放性骨骺发育不全儿童的线性生长。

The overall safety profile of VOXZOGO in children under 5 years of age was similar to that seen in older children..

VOXZOGO在5岁以下儿童中的总体安全性与年龄较大的儿童相似。。

Data from an open-label, long-term Phase 2 extension study was recently presented at the 2023 European Society for Paediatric Endocrinology Meeting in September. Over a four-year period, children aged 2 years and above who received VOXZOGO exhibited a mean (average) height Z-score improvement of 1.1 to 1.4 standard deviations (95% CI limits from 0.46 to 1.93) and a mean height gain of 6.3 to 7.8 centimeters (cm) (95% CI limits from 2.98 to 10.40 cm) when compared to untreated children with achondroplasia of the same age and sex.

最近在9月的2023年欧洲儿科内分泌学会会议上发表了一项开放标签的长期2期延长研究的数据。在四年的时间里，接受VOXZOGO治疗的2岁及以上儿童的平均（平均）身高Z评分改善1.1至1.4个标准差（95%CI限制为0.46至1.93），平均身高增加6.3至7.8厘米（厘米）（95%CI限制为2.98至10.40厘米），与未经治疗的同龄和性别软骨发育不全儿童相比。

In addition, children under the age of 2 years, treated with VOXZOGO for three years, had a mean height Z-score improvement of 0.8 to 1.0 standard deviations (95% CI limits from 0.37 to 1.59) and a height gain between 3.5 and 3.9 cm (95% CI limits from 1.57 to 6.16 cm)..

此外，2岁以下儿童接受VOXZOGO治疗3年，平均身高Z评分改善0.8至1.0标准差（95%CI限制为0.37至1.59），身高增加3.5至3.9厘米（95%CI限制为1.57至6.16厘米）。。

Since the introduction of VOXZOGO in 2021, the company has seen strong patient demand for the medicine worldwide. BioMarin has recently been able to secure increased fill-finish commitments in 2024 and beyond to meet this additional demand. There are approximately 800 children under 5 with achondroplasia in the U.S..

自2021年推出VOXZOGO以来，该公司在全球范围内对该药物的患者需求强劲。BioMarin最近能够在2024年及以后确保增加填充完成承诺，以满足这一额外需求。美国约有800名5岁以下儿童软骨发育不全。。

VOXZOGO is currently approved in Europe in children with achondroplasia who are 2 years of age and older with open growth plates. In September, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending marketing authorization to expand the indication for VOXZOGO for injection to treat children with achondroplasia aged 4 months and older whose epiphyses are not closed.

VOXZOGO目前在欧洲被批准用于2岁及以上患有开放性生长板的软骨发育不全儿童。9月份，欧洲药品管理局（EMA）人用药品委员会（CHMP）通过了积极的意见，建议上市许可，扩大注射用VOXZOGO的适应症，以治疗4个月及以上骨骺发育不全的儿童关闭。

A final approval decision, typically consistent with the CHMP recommendation, is expected from the European Commission later this year.  .

通常与CHMP建议一致的最终批准决定预计将在今年晚些时候从欧盟委员会获得。 .

VOXZOGO is also approved in Japan in children from birth who have achondroplasia with open growth plates. In addition, it is approved in Brazil in children who are 6 months and older with open growth plates as well as in Australia in children with achondroplasia who are 2 years of age and older with open growth plates..

VOXZOGO在日本也被批准用于出生时患有开放性生长板软骨发育不全的儿童。此外，巴西还批准了6个月及以上开放生长板的儿童，澳大利亚批准了2岁及以上开放生长板的软骨发育不全儿童。。

Orphan Drug Designation in Hypochondroplasia

软骨发育不良的孤儿药名称

VOXZOGO also recently received orphan drug designation from the FDA for the treatment of hypochondroplasia, a genetic condition caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene and characterized by impaired bone growth. While similar to achondroplasia, people with hypochondroplasia typically present with milder disproportionality and less severe short stature compared to achondroplasia..

VOXZOGO最近还获得了FDA的孤儿药名称，用于治疗软骨发育不良，这是一种由成纤维细胞生长因子受体3（FGFR3）基因突变引起的遗传性疾病，其特征是骨骼生长受损。虽然类似于软骨发育不全，但与软骨发育不全相比，软骨发育不全的人通常表现出较轻的不成比例和较轻的矮小身材。。

BioMarin plans to initiate a pivotal development program in hypochondroplasia later this year.

BioMarin计划在今年晚些时候启动软骨发育不良的关键发展计划。

About VOXZOGO (vosoritide) for Injection

关于注射用VOXZOGO（vosoritide）

In children with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in FGFR3. VOXZOGO, a C-type natriuretic peptide (CNP) analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth..

在患有软骨发育不全的儿童中，由于FGFR3的功能获得性突变，软骨内骨生长是产生骨组织的重要过程，受到负调控。VOXZOGO是一种C型利钠肽（CNP）类似物，可作为FGFR3下游信号通路的正调节剂，促进软骨内骨生长。。

VOXZOGO is approved in the U.S. and indicated to increase linear growth in children with achondroplasia with open epiphyses. This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

VOXZOGO在美国获得批准，并表示可增加患有开放性骨骺的软骨发育不全儿童的线性生长。基于年度增长速度的提高，该指示在加速批准下获得批准。持续批准可能取决于验证性试验中临床获益的验证和描述。

To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history..

为了满足此上市后要求，BioMarin打算与现有的自然历史相比，使用正在进行的开放标签扩展研究。。

Patient Support Accessing VOXZOGO

患者支持访问VOXZOGO

To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-833-VOXZOGO (1-833-869-9646) or e-mail [email protected]. For more information about VOXZOGO, please visit www.voxzogo.com. For additional information regarding this product, please contact BioMarin Medical Information at [email protected]..

要联系BioMarinRareConnect®案例经理，请致电免费电话，1-833-VOXZOGO（1-833-869-9646）或电子邮件[受电子邮件保护]。有关VOXZOGO的更多信息，请访问www.VOXZOGO.com。有关此产品的更多信息，请通过[电子邮件保护]联系BioMarin医疗信息。。

About Achondroplasia

关于软骨发育不全

Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face, and base of the skull.

软骨发育不全是骨骼发育不良的最常见形式，导致人类身材矮小不成比例，其特征是软骨内骨化减慢，导致长骨，脊柱，面部和颅底的身材矮小和结构紊乱。

This condition is caused by a change in the FGFR3 gene, a negative regulator of bone growth..

这种情况是由FGFR3基因的变化引起的，FGFR3基因是骨骼生长的负调节剂。。

More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births. VOXZOGO is being tested in children whose growth plates are still 'open,' typically those under 18 years of age.

超过80%的软骨发育不全儿童的父母身材平均，并且由于自发基因突变而患病。全球软骨发育不全的发病率约为25000例活产中的一例。VOXZOGO正在测试生长板仍然“开放”的儿童，通常是18岁以下的儿童。

Approximately 25% of people with achondroplasia fall into this category..

大约25%的软骨发育不全患者属于这一类。。

VOXZOGO U.S. Important Safety Information

VOXZOGO美国重要的安全信息

What is VOXZOGO used for?

VOXZOGO用于什么？

VOXZOGO is a prescription medicine used to increase linear growth in children with achondroplasia and open growth plates (epiphyses).

VOXZOGO是一种处方药，用于增加软骨发育不全和开放生长板（骨骺）患儿的线性生长。

VOXZOGO is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

VOXZOGO基于年度增长速度的提高而获得加速批准。持续批准可能取决于验证性试验中临床获益的验证和描述。

What is the most important safety information about VOXZOGO?

关于VOXZOGO最重要的安全信息是什么？

VOXZOGO may cause serious side effects including a temporary decrease in blood pressure in some patients. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, feeling tired, or nausea), patients should eat a meal and drink 8 to 10 ounces of fluid within 1 hour before receiving VOXZOGO..

VOXZOGO可能会导致严重的副作用，包括一些患者血压暂时下降。为了降低血压下降和相关症状（头晕，感到疲倦或恶心）的风险，患者应在接受VOXZOGO前1小时内进餐并饮用8至10盎司的液体。。

What are the most common side effects of VOXZOGO?

VOXZOGO最常见的副作用是什么？

The most common side effects of VOXZOGO include injection site reactions (including redness, itching, swelling, bruising, rash, hives, and injection site pain), high levels of blood alkaline phosphatase shown in blood tests, vomiting, joint pain, decreased blood pressure, and stomachache. These are not all the possible side effects of VOXZOGO.

VOXZOGO最常见的副作用包括注射部位反应（包括发红，瘙痒，肿胀，瘀伤，皮疹，荨麻疹和注射部位疼痛），血液检查中显示的高水平血液碱性磷酸酶，呕吐，关节疼痛，降低血压和胃痛。这些并不是VOXZOGO所有可能的副作用。

Ask your healthcare provider for medical advice about side effects, and about any side effects that bother the patient or that do not go away..

向您的医疗保健提供者咨询有关副作用的医疗建议，以及任何困扰患者或不会消失的副作用。。

How is VOXZOGO taken?

VOXZOGO是如何服用的？

VOXZOGO is taken daily as an injection given under the skin, administered by a caregiver after a healthcare provider determines the caregiver is able to administer VOXZOGO. Do not try to inject VOXZOGO until you have been shown the right way by your healthcare provider. VOXZOGO is supplied with Instructions for Use that describe the steps for preparing, injecting, and disposing VOXZOGO.

VOXZOGO每天作为皮肤下给予的注射，由护理人员在医疗保健提供者确定护理人员能够施用VOXZOGO后由护理人员施用。在您的医疗保健提供者以正确的方式显示之前，不要尝试注射VOXZOGO。提供VOXZOGO使用说明，描述准备，注入和处理VOXZOGO的步骤。

Caregivers should review the Instructions for Use for guidance and any time they receive a refill of VOXZOGO in case any changes have been made..

护理人员应审查指导使用说明以及他们收到VOXZOGO补充的任何时间，以防进行任何更改。。

Inject VOXZOGO 1 time every day, at about the same time each day. If a dose of VOXZOGO is missed, it can be given within 12 hours from the missed dose. After 12 hours, skip the missed dose and administer the next daily dose as usual.

每天大约在同一时间注射VOXZOGO 1次。如果错过了一剂VOXZOGO，可以在错过剂量后12小时内给予。12小时后，跳过错过的剂量，照常服用下一天的剂量。

The dose of VOXZOGO is based on body weight. Your healthcare provider will adjust the dose based on changes in weight following regular check-ups.

VOXZOGO的剂量基于体重。您的医疗保健提供者将在定期检查后根据体重变化调整剂量。

Your healthcare provider will monitor the patient's growth and tell you when to stop taking VOXZOGO if they determine the patient is no longer able to grow. Stop administering VOXZOGO if instructed by your healthcare provider.

您的医疗保健提供者将监测患者的生长情况，并告诉您何时停止服用VOXZOGO，如果他们确定患者不再能够生长。如果您的医疗保健提供者指示，停止管理VOXZOGO。

What should you tell the doctor before or during taking VOXZOGO?

在服用VOXZOGO之前或期间，你应该告诉医生什么？

Tell your doctor about all of the patient's medical conditions including

告诉你的医生关于病人的所有医疗状况，包括

If the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine).

如果患者患有心脏病（心脏或血管疾病），或者患者正在服用血压药物（抗高血压药物）。

If the patient has kidney problems or renal impairment.

如果患者有肾脏问题或肾功能损害。

If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby.

如果患者怀孕或计划怀孕。目前尚不清楚VOXZOGO是否会伤害未出生的婴儿。

If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk.

如果患者是母乳喂养或计划母乳喂养。目前尚不清楚VOXZOGO是否会进入母乳。

Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

告诉医生患者服用的所有药物，包括处方药和非处方药，维生素和草药补充剂。

You may report side effects to BioMarin at 1-866-906-6100. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

您可以在1-866-906-6100向BioMarin报告副作用。鼓励您向FDA报告处方药的不良副作用。访问www.fda.gov/medwatch，或致电1-800-fda-1088。

Please see additional safety information in the full Prescribing Information and Patient Information.

请参阅完整处方信息和患者信息中的其他安全信息。

About BioMarin

关于BioMarin

Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders.

BioMarin成立于1997年，是一家全球生物技术公司，致力于通过基因发现改变生活。该公司开发并商业化针对遗传病根本原因的靶向疗法。BioMarin无与伦比的研究和开发能力为罕见遗传病患者提供了八种转型商业疗法。

The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options.

该公司独特的药物发现方法已经产生了多种商业，临床和临床前候选人，这些候选人解决了重大未满足的医疗需求，具有良好的生物学知识，并提供了首先推销或提供实质性利益的机会超过现有的治疗方案。

For additional information, please visit www.biomarin.com..

欲了解更多信息，请访问www.biomarin.com。。

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including, without limitation, statements about: the potential impact and role of VOXZOGO in children with achondroplasia, including younger children, as well as in the treatment of hypochondroplasia and other genetic short stature conditions; the development of BioMarin's VOXZOGO program, including BioMarin's expectations regarding timing and the ability to obtain final approval decision from the European Commission for the marketing authorization to expand the indication for VOXZOGO; BioMarin's plans for the continued clinical development of VOXZOGO, including ability to maintain continued approval in the U.S.

本新闻稿包含有关BioMarin Pharmaceutical Inc.（BioMarin）商业前景的前瞻性声明，包括但不限于以下声明：VOXZOGO对软骨发育不全儿童（包括年幼儿童）的潜在影响和作用，以及治疗软骨发育不良和其他遗传性矮小状况；BioMarin的VOXZOGO计划的发展，包括BioMarin对时间的期望以及获得欧盟委员会最终批准决定的上市许可的能力，以扩大VOXZOGO的适应症；BioMarin关于VOXZOGO持续临床开发的计划，包括在美国保持持续批准的能力。

based on ongoing label-extension studies and confirmatory trials; BioMarin's plans to initiate a pivotal development program in hypochondroplasia; and BioMarin's expectations regarding the number of children with achondroplasia that could be prescribed with VOXZOGO and related potential benefits. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements.

基于正在进行的标签扩展研究和验证性试验；BioMarin计划启动软骨发育不良的关键发展计划；和BioMarin对可以用VOXZOGO处方的软骨发育不全儿童数量和相关潜在益处的期望。这些前瞻性陈述是预测，涉及风险和不确定性，因此实际结果可能与这些陈述有很大差异。

These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of VOXZOGO; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission (SEC), including, without limitation, the factors contained under the caption 'Risk Factors' in BioMarin's Quarterly Report on Form 10-Q for the quarter en.

这些风险和不确定性包括：VOXZOGO当前和计划的临床前研究和临床试验的结果和时间；在临床试验中持续监测患者中观察到的任何潜在不良事件；欧盟委员会和其他监管机构决定的内容和时间；以及BioMarin与美国证券交易委员会（SEC）提交的文件中详述的那些因素，包括但不限于BioMarin季度10-Q表格季度报告中“风险因素”标题下包含的因素。

BioMarin® and VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc.

BioMarin®和VOXZOGO®是BioMarin Pharmaceutical Inc.的注册商标。

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联络：

Investors

投资者

Media

媒体

Traci McCarty

Traci McCarty。

Andrew Villani

Andrew Continuous Villani

BioMarin Pharmaceutical Inc.

BioMarin制药公司。

BioMarin Pharmaceutical Inc.

BioMarin制药公司。

(415) 455-7558

(415) 455-7558

(628) 269-7393

(628) 269-7393

SOURCE BioMarin Pharmaceutical Inc.

来源BioMarin制药公司。