Sarclisa（isatuximab-irfc）注射剂

公司名称：Sanofi

批准日期：2020年3月2日

治疗：多发性骨髓瘤

Sarclisa（isatuximab-irfc）是CD38定向的溶细胞抗体，与波马利度和地塞米松联合使用可治疗成人多发性骨髓瘤。

新泽西州布里奇沃特，2020年3月2日，美国新闻社/-美国食品药品监督管理局（FDA）批准将Sarclisa（isatuximab-irfc）与pomalidomide和地塞米松（pom-dex）联合用于治疗复发性难治性多发性成年人至少接受过两次来那度胺和蛋白酶体抑制剂治疗的骨髓瘤（RRMM）。  

Sarclisa是一种单克隆抗体，可与多发性骨髓瘤细胞上的CD38受体结合。

赛诺菲首席执行官Paul Hudson表示：“今天的FDA批准Sarclisa为患有难治性多发性骨髓瘤的患者提供了一种新的治疗选择。这些患者的疾病已经复发或对其先前的治疗产生了抵抗力。” “在赛诺菲，我们专注于发现和开发可能会改变医学实践的药物，Sarclisa在美国提供了潜在的新护理标准。我们还将继续在多发性骨髓瘤的综合临床计划中评估Sarclisa就像其他血液癌和实体瘤一样。”

难治性患者的Sarclisa安全性和疗效

在ICARIA-MM研究中，Sarclisa加入pom-dex（Sarclisa联合疗法）后，无进展生存期（PFS）的统计显着改善，中位PFS为11.53个月，而单独使用pom-dex则为6.47个月（HR 0.596， 95％CI：0.44-0.81，p = 0.0010）。与单独的pom-dex相比，Sarclisa联合疗法还显示出明显更高的总体缓解率（60.4％对35.3％，p <0.0001）。

“不幸的是，大多数多发性骨髓瘤患者会复发，并且对当前可用的治疗方法变得难以治疗。Sarclisa与pomalidomide和地塞米松联合使用为美国患有这种无法治愈的疾病的患者提供了重要的新治疗选择，”医学博士Paul Richardson博士说ICARIA-MM的研究员，达纳-法伯癌症研究所Jerome Lipper多发性骨髓瘤中心的临床项目负责人和临床研究总监。 “关键的ICARIA-MM试验是CD38抗体与pom-dex联合使用的第一项3期研究，目前的结果证明了在这种情况下的临床价值。该研究招募了广泛的复发性和难治性多发性骨髓瘤患者，特别是难以治疗且预后不良，这反映了实际操作。”

在接受Sarclisa联合治疗的患者中，最常见的不良反应（发生在20％或更多的患者中）是中性粒细胞减少症（96％），输液相关反应（39％），肺炎（31％），上呼吸道感染（57） ％）和腹泻（26％）。超过5％的接受Sarclisa联合治疗的患者发生了严重的不良反应，其中包括肺炎（25.3％）和发热性中性粒细胞减少症（12.3％）。 7％的患者因不良反应（3-4级）而永久终止Sarclisa联合疗法，而3％的患者因与输注相关的反应而中止。

治疗多发性骨髓瘤的重要新选择

Sarclisa提供静脉（IV）给药，与pom-dex组合以10 mg / kg的剂量每周给药4周，然后每两周给药一次，直至疾病进展或出现无法接受的毒性。第一个周期的注入时间为200分钟，从第三个周期开始可以减少到75分钟。治疗周期为28天。

Sarclisa在美国的定价（批发价或WAC）为每100毫克小瓶650美元和每500毫克小瓶3,250美元。对于美国的典型患者，体重在70-80千克（154-176磅）之间，这意味着每次输液要花费$ 5,200。通常预计患者的实际费用会更低，因为标价不反映保险范围，共付额支持或患者支持计划提供的经济支持。赛诺菲（Sanofi）致力于以负责任的定价，同时为有重大未满足需求的患者提供创新且有价值的疗法。

已在美国开具Sarclisa处方的患者可能有资格参加CareASSIST患者支持计划，该计划为符合条件的患者提供报销支持和经济援助。有关更多信息，请致电1-833-WE + CARE（1-833-930-2273）或访问SanofiCareAssist.com/Sarclisa。

多发性骨髓瘤导致重大疾病负担

多发性骨髓瘤是第二常见的血液系统恶性肿瘤，在美国影响了超过130,000例患者；每年大约有32,000名美国人被诊断出患有多发性骨髓瘤。尽管有可用的治疗方法，但多发性骨髓瘤仍然是无法治愈的恶性肿瘤，并伴有大量患者负担。随着患者的复发，他们可能变得对所接受的治疗无效。需要新的药物，以便随着疾病的发展，患者和医生可以选择。复发（或复发）的多发性骨髓瘤意味着癌症在治疗或缓解一段时间后会复发。由于多发性骨髓瘤无法治愈，因此大多数患者会在某个时候复发。难治性多发性骨髓瘤是指对治疗无反应的癌症。

关于萨克利萨

Sarclisa是一种单克隆抗体（mAb），可与多发性骨髓瘤细胞上的CD38受体结合。它旨在诱导程序性肿瘤细胞死亡（凋亡）和免疫调节活性。 CD38在多个骨髓瘤细胞和细胞表面受体上高度均匀地表达，使其成为基于抗体的治疗药物（例如Sarclisa）的潜在靶标。

Sarclisa拥有FDA和欧洲药品管理局（EMA）的“孤儿药”称号。在2019年第二季度，EMA接受了Sarclisa与pom-dex联合用于某些RRMM患者的市场许可申请的审查。美国以外的任何监管机构尚未对Sarclisa的安全性和有效性进行全面评估。

在进行中的复发性难治性或新诊断的多发性骨髓瘤患者中，结合目前的标准治疗方法，将继续在多个正在进行的3期临床试验中对Sarclisa进行评估。它也正在研究用于治疗其他类型的血液癌症（血液系统恶性肿瘤）和实体瘤。

美国患者的重要安全信息和指示

什么是Sarclisa？

Sarclisa是一种处方药，与pomalidomide和dexamethasone结合使用，可以治疗至少接受过2种先前疗法（包括来那度胺和蛋白酶体抑制剂）的成人，以治疗多发性骨髓瘤。

目前尚不清楚Sarclisa对儿童是否安全有效。

如果您对isatuximab-irfc或Sarclisa中的任何成分有严重的过敏反应史，请不要接受Sarclisa（请参阅完整的处方信息中的成分列表）。

在接受Sarclisa之前，请告知您的医疗保健提供者所有您的医疗状况，包括您是否：

正在怀孕或打算怀孕。 Sarclisa可能会伤害您未出生的婴儿。怀孕期间您不应该接受Sarclisa。

能够怀孕的女性在治疗期间以及最后一次服用Sarclisa后的5个月内应使用有效的节育方法。与您的医疗保健提供者讨论您可以在此期间使用的节育方法。

如果您认为自己在Sarsarsa治疗期间怀孕或怀孕，请立即告诉您的医疗保健提供者。

正在母乳喂养或计划母乳喂养。不知道Sarclisa是否会进入母乳。 Sarclisa治疗期间不应母乳喂养。

告诉您的医疗保健提供者您所服用的所有药物，包括处方药和非处方药，维生素和草药补品。

我将如何接收Sarclisa？

您的医疗保健提供者会通过静脉内（IV）输注给您Sarsarsa。

Sarclisa与药物pomalidomide和dexamethasone的治疗周期为28天（4周）。

在第1周期中，Sarclisa通常每周服用一次。

从第2周期开始，Sarclisa通常每2周给药一次。

您的医疗保健提供者将决定您应该接受Sarclisa多长时间。

如果您错过任何约会，请尽快致电您的医疗保健提供者以重新安排约会。

您的医疗保健提供者会在每次服用Sarclisa之前给您药物，以帮助减少输液反应的风险（使它们减少发生频率和强度）。

Sarclisa可能有哪些副作用？

Sarclisa可能引起严重的副作用，包括：

输液反应。输注反应在Sarclisa中很常见，有时可能很严重。

您的医疗保健提供者将在每次输注Sarclisa之前开药，以帮助降低输注反应的风险或使输注反应的严重程度降低。在每次服用Sarclisa期间，您将被监测输液反应。

如果您有输液反应，您的医护人员可能会减慢或停止输液，或完全停止使用Sarclisa的治疗。

如果在输注Sarclisa期间或之后的24小时内出现以下任何输液反应症状，请立即告知您的医疗保健提供者：

呼吸急促

咳嗽

发冷

恶心

白细胞数量减少。减少的白细胞数量在Sarclisa中很常见，某些白细胞可能会严重减少。您可能会增加某些感染的风险，例如上呼吸道感染和下呼吸道感染。

您的医疗保健提供者将在用Sarclisa治疗期间检查您的血细胞计数。您的医疗保健提供者可能会开具抗生素或抗病毒药来帮助预防感染，或者会在Sarsarsa治疗期间开出有助于增加白细胞计数的药物。

如果在Sarclisa治疗期间出现发烧或感染症状，请立即告知您的医疗保健提供者。

罹患新癌症的风险。 Sarclisa治疗期间人们中发生了新的癌症。您的医疗保健提供者将在使用Sarclisa进行治疗期间监视您是否有新癌症。

血液检查改变。 Sarclisa会影响血液检查的结果以匹配您的血型。在开始使用Sarclisa治疗之前，您的医疗保健提供者将进行血液检查以匹配您的血型。在接受输血之前，请告知所有医疗保健提供者您正在接受Sarclisa治疗。

 Sarclisa最常见的副作用包括：

肺部感染（肺炎）

上呼吸道感染

腹泻

红细胞数量减少（贫血）

血小板计数减少（血小板减少）

这些并不是Sarclisa的所有可能的副作用。有关更多信息，请咨询您的医疗保健提供者或药剂师。

Company: Sanofi
Date of Approval: March 2, 2020
Treatment for: Multiple Myeloma

Sarclisa (isatuximab-irfc) is a CD38-directed cytolytic antibody indicated in combination with pomalidomide and dexamethasone for the treatment of adult patients multiple myeloma.

BRIDGEWATER, N.J., March 2, 2020 /PRNewswire/ -- The U.S. Food and Drug Administration (FDA) has approved Sarclisa (isatuximab-irfc) in combination with pomalidomide and dexamethasone (pom-dex) for the treatment of adults with relapsed refractory multiple myeloma (RRMM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. Sarclisa is expected to be available to patients in the U.S. shortly.

Sarclisa is a monoclonal antibody that binds to the CD38 receptor on multiple myeloma cells.

"Today's FDA approval of Sarclisa provides a new treatment option for patients with difficult-to-treat multiple myeloma. These are patients whose disease has returned or become resistant to their prior treatments," said Paul Hudson, Chief Executive Officer, Sanofi. "At Sanofi, we are focused on discovering and developing medicines that may change the practice of medicine, and Sarclisa offers a potential new standard of care in the United States. We continue to evaluate Sarclisa in a comprehensive clinical program in multiple myeloma, as well as in other blood cancers and solid tumors."

Sarclisa Safety Profile and Efficacy in Difficult-to-Treat Patients

In the ICARIA-MM study, Sarclisa added to pom-dex (Sarclisa combination therapy) demonstrated a statistically significant improvement in progression free survival (PFS) with a median PFS of 11.53 months compared to 6.47 months with pom-dex alone (HR 0.596, 95% CI: 0.44-0.81, p=0.0010). Sarclisa combination therapy also demonstrated a significantly greater overall response rate compared to pom-dex alone (60.4% vs. 35.3%, p<0.0001).  

"Most patients with multiple myeloma unfortunately relapse and become refractory to currently available therapies. Sarclisa used in combination with pomalidomide and dexamethasone offers an important new treatment option for patients in the United States living with this incurable disease," said Paul Richardson, MD, principal investigator of ICARIA-MM, and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. "The pivotal ICARIA-MM trial was the first Phase 3 study of a CD38 antibody in combination with pom-dex to present results demonstrating significant clinical benefit in this setting. The study enrolled a broad population of patients with relapsed and refractory multiple myeloma that is particularly difficult to treat and with poor prognosis, which is reflective of real-world practice."

The most common adverse reactions (occurring in 20% or more of patients) in patients who received Sarclisa combination therapy were neutropenia (96%), infusion-related reactions (39%), pneumonia (31%), upper respiratory tract infection (57%) and diarrhea (26%). Serious adverse reactions that occurred in more than 5% of patients who received Sarclisa combination therapy included pneumonia (25.3%) and febrile neutropenia (12.3%). Permanent discontinuation of Sarclisa combination therapy due to an adverse reaction (Grades 3-4) occurred in 7% of patients, and 3% of patients discontinued due to an infusion-related reaction.

An Important New Option for Treating Multiple Myeloma

Sarclisa offers an intravenous (IV) administration and is dosed at 10 mg/kg, in combination with pom-dex, every week for four weeks and then every two weeks, until disease progression or unacceptable toxicity. The first cycle is administered in an infusion time of 200 minutes, which can decrease to 75 minutes for the third cycle onwards. A treatment cycle is 28 days.

The U.S. list price (wholesale acquisition cost, or WAC) for Sarclisa is $650 per 100 mg vial and $3,250 per 500 mg vial. For a typical patient in the U.S., between 70-80 kg (154-176 lbs), this correlates to a cost of $5,200 per infusion. Actual costs to patients are generally anticipated to be lower as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs. Sanofi is committed to responsible pricing while bringing innovative and valuable therapies to patients with significant unmet need.

Patients in the U.S. who have been prescribed Sarclisa may be eligible to enroll in the CareASSIST Patient Support Program, which provides reimbursement support and financial assistance to eligible patients. For more information, please call 1-833-WE+CARE (1-833-930-2273) or visit SanofiCareAssist.com/Sarclisa.

Multiple Myeloma Leads to Significant Disease Burden

Multiple myeloma is the second most common hematologic malignancy,i affecting more than 130,000 patients in the United States; approximately 32,000 Americansii are diagnosed with multiple myeloma each year. Despite available treatments, multiple myeloma remains an incurable malignancy, and is associated with significant patient burden. As patients relapse, they can become refractory to therapies they have received. There is a need for new agents so that patients and physicians can have options as the disease progresses over time. Relapsed (or recurrent) multiple myeloma means that the cancer returns after treatment or a period of remission. Since multiple myeloma does not have a cure, most patients will relapse at some point. Refractory multiple myeloma refers to cancer that does not respond to therapy.

About Sarclisa

Sarclisa is a monoclonal antibody (mAb) that binds to the CD38 receptor on multiple myeloma cells. It is designed to induce programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and cell surface receptors, making it a potential target for antibody-based therapeutics such as Sarclisa.

Sarclisa has Orphan Drug Designation status from the FDA and the European Medicines Agency (EMA). In the second quarter of 2019, the EMA accepted for review the Marketing Authorization Application for use of Sarclisa in combination with pom-dex for the treatment of certain patients with RRMM. The safety and efficacy of Sarclisa has not been fully evaluated by any regulatory authority outside of the U.S.

Sarclisa continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard treatments for people with relapsed refractory or newly diagnosed multiple myeloma. It is also under investigation for the treatment of other blood cancer types (hematologic malignancies) and solid tumors.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is Sarclisa?

Sarclisa is a prescription medicine used in combination with pomalidomide and dexamethasone to treat adults who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, to treat multiple myeloma.

It is not known if Sarclisa is safe and effective in children.

Do not receive Sarclisa if you have a history of severe allergic reaction to isatuximab-irfc or any of the ingredients in Sarclisa (see the list of ingredients in full Prescribing Information).

Before receiving Sarclisa, tell your healthcare provider about all of your medical conditions, including if you:

· are pregnant or plan to become pregnant. Sarclisa may harm your unborn baby. You should not receive Sarclisa during pregnancy.

o Females who are able to become pregnant should use an effective method of birth control during treatment and for 5 months after your last dose of Sarclisa. Talk to your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you think you are pregnant or become pregnant during treatment with Sarclisa.

· are breastfeeding or plan to breastfeed. It is not known if Sarclisa passes into your breast milk. You should not breastfeed during treatment with Sarclisa.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive Sarclisa?

· Sarclisa will be given to you by your healthcare provider by intravenous (IV) infusion into your vein.

· Sarclisa is given in treatment cycles of 28 days (4 weeks), together with the medicines pomalidomide and dexamethasone.

o In cycle 1, Sarclisa is usually given weekly.

o Starting in cycle 2, Sarclisa is usually given every 2 weeks.

Your healthcare provider will decide how long you should receive Sarclisa.

· If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

· Your healthcare provider will give you medicines before each dose of Sarclisa to help reduce the risk of infusion reactions (make them less frequent and severe).

What are the possible side effects of Sarclisa?

Sarclisa may cause serious side effects, including:

· Infusion reactions. Infusion reactions are common with Sarclisa and can sometimes be severe.

o Your healthcare provider will prescribe medicines before each infusion of Sarclisa to help decrease your risk for infusion reactions or to help make any infusion reaction less severe. You will be monitored for infusion reactions during each dose of Sarclisa.

o Your healthcare provider may slow down or stop your infusion, or completely stop treatment with Sarclisa, if you have an infusion reaction.

Tell your healthcare provider right away if you develop any of the following symptoms of infusion reaction during or within 24 hours after an infusion of Sarclisa: 

· 

o feeling short of breath

o cough

o chills

o nausea

· Decreased white blood cell counts. Decreased white blood cell counts are common with Sarclisa and certain white blood cells can be severely decreased. You may have an increased risk of getting certain infections, such as upper and lower respiratory infections.

Your healthcare provider will check your blood cell counts during treatment with Sarclisa. Your healthcare provider may prescribe an antibiotic or antiviral medicine to help prevent infection, or a medicine to help increase your white blood cell counts during treatment with Sarclisa.

Tell your healthcare provider right away if you develop any fever or symptoms of infection during treatment with Sarclisa.

· Risk of new cancers. New cancers have happened in people during treatment with Sarclisa. Your healthcare provider will monitor you for new cancers during treatment with Sarclisa.

· Change in blood tests. Sarclisa can affect the results of blood tests to match your blood type. Your healthcare provider will do blood tests to match your blood type before you start treatment with Sarclisa. Tell all of your healthcare providers that you are being treated with Sarclisa before receiving blood transfusions.

 The most common side effects of Sarclisa include:

· lung infection (pneumonia)

· upper respiratory tract infection

· diarrhea

· decreased red blood cell counts (anemia)

· decreased platelet counts (thrombocytopenia)

These are not all the possible side effects of Sarclisa. For more information, ask your healthcare provider or pharmacist.

About Sanofi

Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.

With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the globe.

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SOURCE Sanofi

Posted: March 2020