默沙东的抗新冠病毒药片: 你知道和不知道的事实

发布时间：2021-10-05 08:33:25来源：全球医生组织

国际药企巨头默沙东与合作伙伴发布了成功研发抗新冠病毒药片，该新闻瞬间登上各大媒体头条，连锁反应是默沙东的股票飙升，mRNA疫苗厂家的股市下跌。

就连国际顶级权威专家Dr.AnthonyS.Fauci博士也发表评论该药“veryimpressive”。FDA没有给出任何评论。

自从疫情以来，几乎所有新冠疾病和疫情的研究结果总是最先通过新闻形式，公布于众，这已成为了新常态，没人在乎同行评议论文。

从临床医生角度看，口服药片molnupiravir与静脉给药抗病毒方法相比，具有绝对优势和便捷性。每天口服两次药片，持续五天一个疗程。轻中度感染患者或疑似感染的人都能做到。就像感冒初期喝几包板蓝根，休息几天呗！

但是，医界人士仍善意提醒“疫情期间有多少药都说抗新冠病毒，比如吉利德的瑞姆昔韦，就是最亮眼的忽悠案例(美赞“人民的希望”)。

实际上，根据目前公布的信息，专业人士尚不清楚这种抗病毒治疗是否能被广泛应用（首先需要获得FDA-EUA批准）。投资分析家也在预测这种抗新冠病毒药将产生多少亿美元销售额，是否会超过新冠疫苗的获益？

如果我们静心琢磨默沙东这款抗新冠病毒药molnupiravir，再对比其他药企在研的抗病毒药，包括中医抗病毒方剂(实战验证有效的)，仍有许多问题没有得到解答。

如果是针对轻中度新冠病毒感染疾病患者，值得临床专家开展“头对头”的临床试验，比较中药抗新冠病毒方剂和默沙东的抗病毒药molnupiravir。

唯一困惑的是中医抗新冠肺炎“处方剂”似乎太多、太多了，不知道选择哪个更具有代表性？

抗新冠病毒药如何被证明确有其效？

根据媒体报道，默沙东抗新冠病毒药molnupiravir之所以成功，重要原因之一是尽早给予抗病毒药，帮助轻中度感染患者或无症状患者不会发展成为重症。因此，可预测减少患者住院率50%（这也是临床观察终点?）。

被媒体称之为改变“游戏规则”的救命药molnupiravir能做到这一点很不容易了，而其他抗病毒药并没有展示出如此明确效果，比如瑞姆昔韦不仅需要静脉滴注三天给药，仅仅是缩短了住院病程时间(临床观察终点)。

molnupiravir安全性如何?

Obviously,adruggivenearlyinCovidneedsacleansafetyprofile.Sofar,thedataincludedinthepressreleaselookverygood.

Patientsintheplaceboarmwerethreetimesmorelikelytowithdrawfromthestudyduetoapparentsideeffectsthanthosewhoactuallyreceivedmolnupiravir.ThatlikelymeansthesideeffectsofCovidwereworsethanthoseofthedrug.

Butonlysomuchcanbeseenfromthatkindofdata.MolnupiravirworksbymessingupthewaytheviruscopiesRNA,itsgeneticmaterial,preventingviralreplication.

Thereissomeconcernitcouldbemutagenic,meaningthatitcouldcausemutations.Oneresultcouldbethatitcausesbirthdefects.Intheclinicaltrial,bothwomenandmenweretoldtoeitherabstainfromsexualintercourseortousecontraceptionwhiletheyweretakingthedrugandforatleastfourdaysafter.Womenofchildbearingagealsoneededanegativepregnancytesttostarttakingthemedicine.

Couldtherebeothereffects?

InaconferencecallwithreportersFriday,DariaHazuda,atopMerckvirologist,saidthatMerckandRidgebackhadstudiedthemutagenicpotentialofthedruginbothcelllinesandinanimalmodelsthatareroutinelyusedindrugdevelopmentandwhichareacceptedbyregulatoryagencies.

“Iwouldsaythatinallofthemodelswherewehavelooked,wehaveseennoevidenceofthepotentialformutagenicityforthisagent,”Hazudasaid.

“We’reverycomfortablethatthedrugwillbesafeifusedasintendedandattheconcentrationswherewehavelookedandintheconcentrationswhichweareachievinginpatients.”

只有那些未接种疫苗的患者用molnupiravir?

Merck’strialwasconductedentirelyinpatientswhohadnotbeenvaccinated.Thatmadeitmucheasiertoshowthatthemedicinecanreducehospitalizationanddeath—becausepatientswhohavenotpreviouslybeenvaccinatedaremorelikelytobehospitalizedordie.

Butdoesthatmeanthat,inpractice,thedrugwillonlybeusedinunvaccinatedpatients,orwillitbeusedincasesofbreakthroughinfections?It’shardtosay.Patientswithbreakthroughinfectionsareatlowerriskofhospitalization,whichcouldchangetherisk-benefitcalculusaroundthemedicine.

该药未来市场规模预期有多大?

DainaGraybosch,ananalystatSVBLeerink,forecastinanotetoinvestorsonMondaymorningthatmolnupiravirsaleswillpeaknear$5billionayearin2022.

Builtintothisareanumberofassumptions,amongthemthatthefirst-moveradvantagewillmeanthatMerckandRidgebackwillbeusedmorethantheotherpillsindevelopmentandthatunvaccinatedpatientswithbreakthroughinfectionswillbeeligibletoreceivethedrug,too.

TimothyAndersonofWolfeResearch,astandaloneequitiesresearchfirm,takestheotherside,essentiallysayingitistoosoontoputanumberonmolnupiravirsales,inpartbecausedatafromcompetingfirmsarenotavailablebutalsobecauseotherquestionsremain.

“VaccinationratescontinuetoriseintheUSandotherdevelopedmarkets,meaningthecohortofpatientswhowouldqualifyformolnupiravir(i.e.mostlythosewhoareunvaccinated,athigherrisk)willshrinkovertime,”Andersonwroteinanotetoclients.

Successfullyusingthedrug,hepointedout,willalsorequirethatpatientsgettestedearlyintheirdiseasecourse.Ifpeoplestarttoskipgettingtested,theywon’treceivemolnupiravir.

该药品预期售价多少？谁付费？

Mostanalystsarebasingthecostofmolnupiravironthe$1.2billiontheU.S.governmentspenttolockup1.7millioncoursesofthemedicine,whichworksoutto$700perfivedaycourse.

ButAndersonpointsoutthatthecostforanewpilltotreatinfluenzadevelopedbyRocheisjust$150percourse.Willthe$700priceholdup?

Questionsaboutpaymentanddistributioncouldplayabigroleinhowbigthemarketformolnupiravirgets.

Andersonassumesinhisnotetoclientsthat,intheU.S.,insurancecompanieswillbepayingforthedrugthroughtraditionalchannels.Heexpectsthatat$700,insurerswillrestrictuseofthedrugtothosewhoareunvaccinatedandhavemultipleriskfactorsfordisease—basicallysimilarprofilestothosewhoareinthetrials.

Butit’salsopossiblethatsalesintheU.S.mightbemostlytothegovernment.Thisishowthingshaveworkedwithbothremdesivir,usedinhospitalizedpatients,andthemonoclonalantibodiesdevelopedbyRegeneronandEliLilly.Willthegovernmenthandlethedistributionofapillgrantedanemergencyuseauthorizationinthesamewaythatithashandledthemonoclonals?

若该药进入临床，是否影响疫苗接种和其他疗法应用？

Itdoesn’tmakeanysensetoforegoaCovidvaccinebecauseapilltotreatthediseaseexists.

Thebenefitsareadditive,andsomeonewhogotabreakthroughinfectionandthenthepillhasamuchlowerriskofhospitalizationthansomeonewhojustreliedonthepill.

Butitseemslikelythatsomepeoplewillfeellessurgencytogetvaccinatedasaresultofmolnupiravir’sexistence,andsharesinPfizer,BioNTech,andModernaallfellonFriday.ThelattertwoaredownagainMondaymorning.

SharesinRegeneronalsofell,asoraldrugscreateuncertaintyforitsmonoclonalantibodytreatmentforCovid.

Thelandscapethereisuncertain,withothercompaniescomingforwardwithantibodiesthatmayhaveadvantages.

Onesmallfirm,AdagioTherapeutics,recentlypresentedearlydataonanantibodyitthinkscouldbegivenasasingleshot.

Thisissimple:itdoesn’t.Butit’sworthtakingalookatwhatdataareavailableforeach.

Ivermectin,ironically,isanotherMerckdrug.Thecompany’sdonationofthemedicinetobeusedtocombataparasiticdiseasecalledriverblindnessisoneofthegreatexamplesofpharmaceuticalphilanthropy.It’salsousedasaveterinarydrugtotreatheartworm.

Earlyinthepandemic,therewerestudiesincellculturesthatshowedthativermectinandanotherdrug,hydroxychloroquine,mightbeworthtestingasCovid-19treatments.

Multiplestudieshavefailedtoshowabenefitforhydroxychloroquine,butthepictureismurkierforivermectin.Still,oneofthelargeststudiesshowingabenefitwaswithdrawnduetowidespreadflaws.

ThereisastudyconductedinBrazil,theTogetherTrial,thattestedathree-daycourseofivermectincomparedtoplaceboandshowedtherewasnobenefitonhospitalizationsandERvisits.

Thatwouldmakeitunlikelythativermectin,anoldantiparasitic,wouldhaveefficacyapproachingthisnewerantiviral.

Drugcompaniesareunlikelytoconductlarge,rigorousstudiesofoldergenericmedicines—althoughNovartisdidbegin,thenstop,ahydroxychloroquinestudy.ButrightnowitisunlikelythativermectinistheoralCovidmedicinetheworldneeds.Molnupiravir,ontheotherhand,mightbe.

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主讲：时占祥博士

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讲座内容简介：

疫情期间，全球数字健康和数字医疗蓬勃发展。凭借惊人增长速度，权威机构预测到2025年将达6600亿美元规模。

2020-2021年期间，投资数字健康和数字医疗领域创下了始料未及的新高。随着医疗健康初创公司和传统医疗机构迈入了数字化新时代，无论政府、企业、风投，甚至传统医疗机构都在变化中，而且，这种变化是不可逆转的。

未来属于数字健康和数字医疗。大批数字医疗初创企业已经继续扩展并证明这一观点和发展趋势。

我们根据2021年度TOP100数字健康百强企业案例，与业界同仁探讨哪些技术、数字化产品、疾病领域和商业模式值得借鉴和参考。

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