Gilead Sciences Statement on Request to Rescind Remdesivir orphan Drug Designation Gilead has submitted a request to the U.S. Food and Drug Administration to rescind the orphan drug designation it was granted for the investigational antiviral remdesivir for the treatment of COVID-19 and is waiving all benefits that accompany the designation. Gilead is confident that it can maintain an expedited timeline in seeking regulatory review of remdesivir, without the orphan drug designation. Recent engagement with regulatory agencies has demonstrated that submissions and review relating to remdesivir for the treatment of COVID-19 are being expedited. 
In early March, Gilead sought and was subsequently granted an orphan drug designation for the remdesivir as a potential treatment for COVID-19. orphan drug designation is granted by the FDA in situations where the disease affects fewer than 200,000 patients in the United States. 
Among the benefits of orphan drug designation, this status results in a waiver of the requirement to provide a pediatric study plan prior to the submission of a New Drug Application – a process that can to take up to 210 days to review. 
Gilead recognizes the urgent public health needs posed by the COVID-19 pandemic.  The company is working to advance the development of remdesivir as quickly as possible, and will provide updates as they become available.

日前，吉利德科學公司的在研抗病毒療法瑞德西韋（remdesivir）獲得美國FDA授予的孤兒藥資格（orphan drug designation），適應癥為新冠病毒�。–OVID-19）。這一消息引起了不少爭議，有些業(yè)界人士擔心孤兒藥資格可能會影響瑞德西韋的可及性。今日，吉利德科學（Gilead Sciences）公司發(fā)布聲明，宣布已經(jīng)向美國FDA提出申請，要求 FDA收回授予瑞德西韋的孤兒藥資格，并且放棄與孤兒藥資格相關的所有優(yōu)惠權益。

吉利德科學表示，有信心即使在沒有孤兒藥資格的情況下，仍能保持瑞德西韋監(jiān)管審評過程的加速完成。近日該公司與監(jiān)管機構的交流表明，與瑞德西韋治療COVID-19相關的申請和審評都將被加快。

在3月初，吉利德科學向FDA尋求獲得孤兒藥資格，開發(fā)瑞德西韋作為治療COVID-19的潛在療法。孤兒藥資格是FDA鼓勵開發(fā)治療罕見病的措施之一，為醫(yī)藥公司開發(fā)在研療法提供多種優(yōu)惠政策。其中一項優(yōu)惠是可以免去在新藥申請前遞交兒科研究計劃（pediatric study plan）。這一過程的審評時間可能長達210天。

吉利德科學公司在聲明中表示：“ 吉利德認識到COVID-19大流行病帶來的緊急公共衛(wèi)生需求。公司正在以盡可能快的速度推進瑞德西韋的開發(fā)�！�

瑞德西韋是受到廣泛關注的抗病毒在研療法，它目前在6項臨床試驗中接受檢驗，治療不同類型的COVID-19患者。其中，在中國進行的兩項臨床試驗有望在4月份獲得結(jié)果。

3月23日，F(xiàn)DA官網(wǎng)數(shù)據(jù)庫顯示，FDA授予吉利德科學（Gilead Sciences）公司開發(fā)的在研抗病毒療法瑞德西韋（remdesivir）孤兒藥資格（Orphan Drug Designation），其適應癥為冠狀病毒疾病2019（COVID-19）。

 

 

FDA的孤兒藥資格認定項目旨在促進治療罕見疾病或狀況的藥物或生物制品的開發(fā)。罕見疾病的定義是在美國患病人數(shù)小于20萬人。獲得孤兒藥資格的在研療法能夠獲得一系列促進藥物開發(fā)的優(yōu)惠，其中重要的一條是如果該療法的孤兒藥適應癥獲得批準，該藥物可以在這一適應癥方面享有7年市場獨占期（exclusivity）。意味著如果FDA批準瑞德西韋用于治療COVID-19，7年內(nèi)其它醫(yī)藥公司開發(fā)的仿制藥不能在美國上市。除此以外，在藥物開發(fā)過程中，研發(fā)公司還能夠獲得與合格臨床測試相關的稅務抵免，以及遞交新藥申請時特定費用的減免等其它優(yōu)惠。

 

吉利德科學公司開發(fā)的瑞德西韋近來成為大家關注的熱點藥物。它是一款抗病毒療法，其作用機制為抑制RNA依賴性RNA聚合酶的活性，從而抑制RNA病毒的增殖。目前，吉利德公司正在進展6項臨床試驗，檢驗瑞德西韋治療不同類型的COVID-19患者的療效。其中，在中國進行的兩項臨床試驗有望在4月獲得結(jié)果。

 

為了滿足可能出現(xiàn)的未來需求，該公司已經(jīng)擴大瑞德西韋的生產(chǎn)能力，并且將生產(chǎn)兩種瑞德西韋的配方（液體和凍干）。昨日，該公司表示，目前正在將提供個人同情使用（compassionate use）緊急通道過渡到擴展使用項目（expanded access programs），這種方法將加速重癥患者獲得瑞德西韋的機會，并能夠收集所有參與患者的數(shù)據(jù)。這些項目目前正在與全球各國監(jiān)管機構聯(lián)合快速開發(fā)。

3月18日，眾所期待的洛匹那韋-利托那韋治療新冠臨床試驗結(jié)果，在《新英格蘭醫(yī)學雜志》上發(fā)布，結(jié)果讓人失望，在重癥患者中，與常規(guī)治療相比，研究未能觀察到洛匹那韋-利托那韋治療的有效性。

2月初，旨在評估洛匹那韋-利托那韋治療新冠的臨床試驗，在武漢金銀潭醫(yī)院開展。

試驗共納入199名新冠病毒確診患者，隨機接受常規(guī)治療組，和常規(guī)治療加匹那韋-利托那韋治療。臨床改善和病毒清除情況是兩個關鍵指標，結(jié)果顯示：

臨床癥狀改善：兩組患者出現(xiàn)臨床狀況改善中位時間相同，均為16天。洛匹那韋-利托那韋組與常規(guī)治療組患者的風險比為1.31（95% 置信度，0.95-1.80），未能表現(xiàn)出顯著差異。

病毒清除情況：與常規(guī)治療組相比，洛匹那韋-利托那韋沒有降低病毒RNA載量，也無法縮短檢出病毒RNA的時間。試驗結(jié)束時（第28天），洛匹那韋-利托那韋組有40.7%的患者仍可檢出新冠病毒RNA，和常規(guī)治療組無差異。

此外，在安全性方面，洛匹那韋-利托那韋組患者出現(xiàn)了4起胃腸道嚴重不良事件（包括惡心、嘔吐和腹瀉），而常規(guī)治療組未發(fā)生胃腸道嚴重不良事件。

綜合結(jié)果是：和常規(guī)治療相比，洛匹那韋-利托那韋治療，在改善臨床癥狀和清除病毒方面并無優(yōu)勢，還有可能增加不良反應。

關于洛匹那韋-利托那韋

洛匹那韋-利托那韋，商品名克力芝，2000年獲FDA批準上市，用于治療艾滋病。

在此前的SARS疫情和MERS疫情爆發(fā)后，洛匹那韋-利托那韋都作為有潛力的治療藥物，但在臨床試驗中，都沒有產(chǎn)生確鑿的有效證據(jù)。

針對COVID-19，洛匹那韋-利托那韋還是無效。現(xiàn)在，只能期待瑞德西韋臨床數(shù)據(jù)了。

關于二期請點擊：剛剛！美國Remdesivir (瑞德西韋)治療COVID-19適應性設計來了！二期擬入組394例采用7分類有序變量作為主要終點

以下是三期臨床試驗方案：

Arm	Intervention/treatment
Experimental: Remdesivir (RDV), 5 Days Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, and 5.	Drug: Remdesivir Administered as an intravenous infusion Other Name: GS-5734™                      Drug: Standard of Care Standard of care therapy per local written policies or guidelines
Experimental: Remdesivir, 10 Days Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10.	Drug: Remdesivir Administered as an intravenous infusion Other Name: GS-5734™                      Drug: Standard of Care Standard of care therapy per local written policies or guidelines
Active Comparator: Continued SOC Therapy Participants will receive continued standard of care therapy.	Drug: Standard of Care Standard of care therapy per local written policies or guidelines

Outcome Measures

 

Primary Outcome Measures :

1. Proportion of Participants Discharged by Day 14 [ Time Frame: First dose date or randomization date up to 14 days ]
   

               

Secondary Outcome Measures :

1. Proportion of Participants With Treatment Emergent Adverse Events Leading to Study Drug Discontinuation [ Time Frame: First dose date up to 10 days ]

Eligibility Criteria

Ages Eligible for Study:	18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

           

Criteria

   

Key Inclusion Criteria:

• Willing and able to provide written informed consent prior to performing study procedures

• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization

• Currently hospitalized with fever defined as temperature ≥ 36.6 °C armpit, ≥ 37.2 °C oral, or ≥ 37.8 °C rectal

• Peripheral capillary oxygen saturation (SpO2) > 94% on room air at screening

• Radiographic evidence of pulmonary infiltrates

Key Exclusion Criteria:

• Participation in any other clinical trial of an experimental treatment for COVID-19

• Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to study drug dosing

• Requiring mechanical ventilation at screening

• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)

• Creatinine clearance < 50 mL/min

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Brief Summary:

 

The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens compared to standard of care (SOC), with respect to the time to discharge in participants with moderate coronavirus disease (COVID-19).

     

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Remdesivir               Drug: Standard of Care	Phase 3

Study Design 

Study Type :	Interventional                 (Clinical Trial)
EstimatedEnrollment :	600 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Moderate COVID-19 Compared to Standard of Care Treatment
Estimated Study Start Date :	March 2020
Estimated Primary Completion Date :	May 2020
Estimated Study Completion Date :	May 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Remdesivir (RDV), 5 Days Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, and 5.	Drug: Remdesivir Administered as an intravenous infusion Other Name: GS-5734™                      Drug: Standard of Care Standard of care therapy per local written policies or guidelines
Experimental: Remdesivir, 10 Days Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10.	Drug: Remdesivir Administered as an intravenous infusion Other Name: GS-5734™                      Drug: Standard of Care Standard of care therapy per local written policies or guidelines
Active Comparator: Continued SOC Therapy Participants will receive continued standard of care therapy.	Drug: Standard of Care Standard of care therapy per local written policies or guidelines

Outcome Measures

Primary Outcome Measures :

1. Proportion of Participants Discharged by Day 14 [ Time Frame: First dose date or randomization date up to 14 days ]
   

   
               

Secondary Outcome Measures :

1. Proportion of Participants With Treatment Emergent Adverse Events Leading to Study Drug Discontinuation [ Time Frame: First dose date up to 10 days ]

Eligibility Criteria

Ages Eligible for Study:	18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

           

Criteria

   

Key Inclusion Criteria:

• Willing and able to provide written informed consent prior to performing study procedures

• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization

• Currently hospitalized with fever defined as temperature ≥ 36.6 °C armpit, ≥ 37.2 °C oral, or ≥ 37.8 °C rectal

• Peripheral capillary oxygen saturation (SpO2) > 94% on room air at screening

• Radiographic evidence of pulmonary infiltrates

Key Exclusion Criteria:

• Participation in any other clinical trial of an experimental treatment for COVID-19

• Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to study drug dosing

• Requiring mechanical ventilation at screening

• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)

• Creatinine clearance < 50 mL/min

Note: Other protocol defined Inclusion/Exclusion criteria may apply.