코로나백신, 임상 성공일까?

[보타니카]

모더나가 발표한 자료를 궁금해 하실 분들 있을 것 같아 제 블로그에 정리해본 것을 올립니다.

https://blog.naver.com/minervapharmowl/221970421116

모데나(Moderna, 모더나)의 mRNA 백신 (mRNA-1273)의 임상시험 1단계가 성공적으로 끝났다는 소식이다.

기사들을 보면 모든 환자에게서 항체가 생성된 것으로 보도 되었지만, 모데나에서 발표한 자료를 잘 살펴보면 실제 코로나 바이러스를 무력화 시키는 항체(중화항체, neutralizing antibody)는 45명중 8명에게서 형성되었다.

(모든 사람에게 항체가 형성되었다는 것은 바이러스에 붙는 항체가 형성되었다는 뜻. 바이러스를 무력화 시키는 진짜 유효한 항체 아니고)

시험은 백신의 용량별로 25㎍, 100㎍, 250㎍ 을 15명에게 주사하는 것으로 설계되었다(1,2차 두번). 이중 25㎍, 100㎍ 용량에서만 중화항체가 생성되었다. 그렇다면 250㎍을 투여받은 15명은 제외하고, 나머지 용량을 투여받은 30명중 8명이 중화항체가 생성되었으므로 26.7% 정도의 효력을 가지는 것이다. 소수로 진행된 임상1단계의 결과이므로 앞으로 수백, 수천명을 대상으로 진행될 임상2, 3 단계는 더 좋은 결과 나오기를 바라며 주의 깊게 살펴보아야 할 것이다.

더불어 쥐를 대상으로 한 전임상에서, 백신을 맞은 쥐의 폐에서 코로나 바이러스의 복제가 억제되는 것이 발견되었다. 쥐에서 코로나 바이러스의 증식을 억제하는 역가와 8명의 중화항체를 형성한 역가가 일치했다. 이 점을 긍정적으로 보고 Moderna는 임상2단계를 곧 시작할 것이고, 7월에는 임상3단계로 들어갈 예정이다.

현재 대량생산을 위한 생산 시설도 확충하고 있다.

부작용 측면에서는 100㎍ 투여한 1명의 환자가 grade 3 정도의 주사 맞은 부위에 홍반을 보였다.

250㎍에서는 2차 접종후 3명의 환자에게서 grade 3 이상의 전신적 부작용이 나타났으나, 오래 지속되지는 않았다.

250㎍은 앞으로 제외될 예정이니 현재까지 mRNA-1273은 안전한 백신인 것으로 보인다.

부작용 단계

grade 1 : mild AE (adverse effect)

grade 2 : moderate AE

grade 3 : severe AE

grade 4 : life-threatening or disabling AE

grade 5 : death related AE

26.7%라는 결과에는 조금 실망했다.

하지만 그 간 Moderna에서 백신 개발을 위해 달려온 과정을 보니, 우리나라 기업 씨젠과 참 닮아있어 감탄을 금할 수 없었다.

1월 11일 미국 국립생물공학 정보센터 (NCBI)에 코로나 19 유전자 염기 서열이 떴고, 씨젠은 16일에 사내 회의를 통해 진단시약 개발 제안, 21일 개발에 착수했고 2주만에 개발을 완료해 2월 7일 유럽의 인정, 12일에는 우리 나라 식품안전처로부터 긴급사용 승인을 받았다.

Moderna와 NIH도 1월 11일 유전자 염기 서열이 뜬것을 보고, 염기 서열 분석해 13일에 mRNA-1273을 완성한다. 이때 NIAID에서는 임상을 진행하기로 결정하고, 2월 7일에는 임상을 위한 백신을 생산했다. 3월 4일에는 FDA의 승인을 받고, 3월 16일에는 임상에 들어갔으며 4월말에는 유효한 결과를 얻었다. FDA에서 5월 7일에는 임상2단계를 승인했고, Moderna는 7월 임상3단계를 위한 프로토콜을 마무리하고 있다.

나는 글로 써보면서도 긴박한 마음이 드는데, 실제 이 과정을 해낸 사람들은 얼마나 바쁘고, 치열하게 움직인걸까.

이렇게 위기에 눈코뜰새없이 바쁘게 움직였을 과학자들이며 관련 부처 관료들에게도 감사한 마음이든다.

부디 임상 2단계와, 3단계에서 좋은 결과 있기를!

임상이 잘나오면 올 가을부터 의료진들에게는 긴급 사용하게 될 수 있을 거라는데, 이 때쯤 치료제도 같이 나와서 코로나를 어서 물리치면 좋겠다. 개인적으로 나파모스타트가 임상이 잘나오면 더 빠르고 쉽게 일반에게 적용할 수 있지 않을까 싶다. 신종플루 때는 타미플루라는 치료제가 있어서 지금처럼 큰 충격이 오지는 않았었으니...

---

<다음은 moderna 홈페이지의 원문>

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-interim-phase-1-data-its-mrna-vaccine

Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against Novel Coronavirus | Moderna, Inc.

After two doses all participants eval‎uated to date across the 25 µg and 100 µg dose cohorts seroconverted with binding antibody levels at or above levels seen in convalescent sera mRNA-1273 elicited neutralizing antibody titer levels in all eight initial participants across the 25 µg and 100 µg

investors.modernatx.com

CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 18, 2020-- Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today announced positive interim clinical data of mRNA-1273, its vaccine candidate against novel coronavirus (SARS-CoV-2), from the Phase 1 study led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

Immunogenicity data are currently available for the 25 µg and 100 µg dose level (ages 18-55) after two doses (day 43) and at the 250 µg level (ages 18-55) after one dose (day 29). Dose dependent increases in immunogenicity were seen across the three dose levels, and between prime and boost within the 25 µg and 100 µg dose levels. All participants ages 18-55 (n=15 per cohort) across all three dose levels seroconverted by day 15 after a single dose. At day 43, two weeks following the second dose, at the 25 µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from COVID-19) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera. Samples are not yet available for remaining participants.

At this time, neutralizing antibody data are available only for the first four participants in each of the 25 µg and 100 µg dose level cohorts. Consistent with the binding antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in all eight of these participants, as measured by plaque reduction neutralization (PRNT) assays against live SARS-CoV-2. The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.

mRNA-1273 was generally safe and well tolerated, with a safety profile consistent with that seen in prior Moderna infectious disease vaccine clinical studies. The sole incidence of a grade 3 adverse event in the 25 µg and 100 µg dose cohorts was a single participant at 100 µg who experienced grade 3 erythema (redness) around the injection site. To date, the most notable adverse events were seen at the 250 µg dose level, comprising three participants with grade 3 systemic symptoms, only following the second dose. All adverse events have been transient and self-resolving. No grade 4 adverse events or serious adverse events have been reported.

Preclinical results from a viral challenge study in mice conducted in collaboration with NIAID and its academic partners are also available. In this study, vaccination with mRNA-1273 prevented viral replication in the lungs of animals challenged with SARS-CoV-2. Neutralizing titers in Phase 1 clinical trial participants at the 25 µg and 100 µg dose levels were consistent with neutralizing titers that were protective in the mouse challenge model.

Based on the interim Phase 1 data, the Moderna-led Phase 2 study will be amended to study two dose levels, 50 µg and 100 µg, with the aim of selecting a dose for pivotal studies. The NIAID-led Phase 1 study is being amended to include a 50 µg dose level cohort across each of the three age groups. Moderna anticipates the dose for the Phase 3 study to be between 25 µg and 100 µg and expects Phase 3 trial initiation in July​, subject to finalization of the clinical trial protocol.

“These interim Phase 1 data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 µg,” said Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna. “When combined with the success in preventing viral replication in the lungs of a pre-clinical challenge model at a dose that elicited similar levels of neutralizing antibodies, these data substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials.”

“With today’s positive interim Phase 1 data and the positive data in the mouse challenge model, the Moderna team continues to focus on moving as fast as safely possible to start our pivotal Phase 3 study in July and, if successful, file a BLA,” said Stéphane Bancel, Chief Executive Officer at Moderna. “We are investing to scale up manufacturing so we can maximize the number of doses we can produce to help protect as many people as we can from SARS-CoV-2.”

---

<mRNA-1273의 임상시험까지 과정>

https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19

Moderna’s Work on a Potential Vaccine Against COVID-19

On January 11, 2020, the Chinese authorities shared the genetic sequence of the novel coronavirus. On January 13, 2020, the U.S. National Institutes of Health (NIH) and Moderna’s infectious disease research team finalized the sequence for mRNA-1273, the Company’s vaccine against the novel coronaviru...

www.modernatx.com

Timeline of our response through May 7, 2020

○On January 11, 2020, the​ Chinese authorities shared the genetic sequence of the novel coronavirus.

○On January 13, 2020, the U.S. National Institutes of Health (NIH) and Moderna’s infectious disease research team finalized the sequence for mRNA-1273, the Company’s vaccine against the novel coronavirus. At that time, the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, disclosed their intent to run a Phase 1 study using the mRNA-1273 vaccine in response to the coronavirus threat and Moderna mobilized toward clinical manufacture. Manufacture of this batch was funded by the Coalition for Epidemic Preparedness Innovations (CEPI).

○On February 7, 2020, the first clinical batch, including fill and finishing of vials, was completed, a total of 25 days from sequence selection to vaccine manufacture. The batch then proceeded to analytical testing for release.

○On February 24, 2020, the clinical batch was shipped from Moderna to the NIH for use in their Phase 1 clinical study.

○On March 4, 2020, the U.S. Food and Drug Administration (FDA) completed its review of the Investigational New Drug (IND) application filed by the NIH for mRNA-1273 and allowed to the study to proceed to begin clinical trials.

○On March 16, 2020, the NIH announced that the first participant in its Phase 1 study for mRNA-1273 was dosed, a total of 63 days from sequence selection to first human dosing. This Phase 1 study will provide important data on the safety and immunogenicity of mRNA-1273. Immunogenicity means the ability of the vaccine to induce an immune response in participants. The open-label trial is expected to enroll 45 healthy adult volunteers ages 18 to 55 years over approximately six weeks.

○On March 23, 2020, Moderna filed a Current Report on Form 8-K which included, among other things, information regarding the potential timing of the availability of a vaccine against COVID-19. The Company reported that the Phase 1 study is proceeding in accordance with the protocol under the direction of NIAID. The Company further reported that while a commercially-available vaccine is not likely to be available for at least 12-18 months, it is possible that under emergency use, a vaccine could be available to some people, possibly including healthcare professionals, in the fall of 2020. Any emergency use would be subject to authorization by the appropriate regulatory agencies, based on the emergence of clinical data for mRNA-1273 that would support use of the vaccine prior to licensure. In addition, the Company confirmed that it is scaling up manufacturing capacity toward the production of millions of doses per month, in the potential form of individual or multi-dose vials. As has previously been disclosed, the ability of the Company to make millions of doses per month is contingent on investments in the scale up and further buildout of the Company’s existing manufacturing infrastructure.

○On March 27, 2020, the NIH announced that Emory University in Atlanta will begin enrolling healthy adult volunteers ages 18 to 55 years in the NIH-led Phase 1 study of mRNA-1273.

○On April 16, 2020, Moderna announced an award from U.S. government agency BARDA for up to $483 million to accelerate development of mRNA-1273. This award will fund the development of mRNA-1273 to FDA licensure and manufacturing process scale-up to enable large-scale production in 2020 for pandemic response. Moderna plans to hire 150 new team members to support these efforts. Moderna also announced that the NIH-led Phase 1 study of mRNA-1273 has completed enrollment of three dose cohorts (25 µg, 100 µg and 250 µg) and is expanding to an additional six cohorts of older adults and elderly adults.

○On April 27, Moderna announced that it submitted an IND to the U.S. FDA for Phase 2 study of mRNA-1273

○On May 1, Moderna and Lonza announced a worldwide strategic collaboration to manufacture mRNA-1273 with the goal to enable manufacturing of up to 1 billion doses per year

○On May 6, Moderna filed a Current Report on Form 8-K, which included an interview published by National Geographic with Anthony S. Fauci, M.D., Director of NIAID, which described his assessment of the results of certain preclinical testing related to the ongoing Phase 1 clinical study of mRNA-1273.

○On May 7, Moderna announced that the FDA completed its review of the Company’s IND application for mRNA-1273 allowing it to proceed to Phase 2 study, expected to begin shortly. Moderna is finalizing protocol for Phase 3 study of mRNA-1273, expected to begin in early summer of 2020.

---

<mRNA-1273의 작동원리 동영상>

https://youtu.be/qJlP91xjvsQ

                            

​

mRNA-1273 을 주사하면 mRNA가 면역세포 안으로 들어가서 바이러스의 스파이크를 면역세포에 생성한다.

이후 다른 면역세포들이 이 스파이크와 접한뒤 항체를 생성하는 것이다.

일반 백신보다 속도가 빠르고, 간단하게 항체를 생성하게 하는 이점이 있다.

[Jinsook]

글 감사합니다^^

[봄날처럼]

45명중 8명만 항체가 생겼다면 백신으로 쓰기에는 너무 낮은비율 아닌가

[보타니카]

250용량은 빼고, 30명중 8명으로 보는게 맞을 것 같아요

[봄날처럼]

30명중 8명도 넘적은 확율인데

[랄프놀래]

바이러스 변이가 심해서 방어라는 표현보다 임상증상 완화 정도의 역할은 할 수 있겠네요 좋은 정보 감사드려요

[보타니카]

그렇죠, 변이도 심하니, 잘되길 바라지만 그저 밝게만 보는 시각은 위험한 것 같아요

[코두]

주식을 떠나 효과적인 치료제가 나와서 어서 종식됐으면 좋겠네요. 생활이 답답해요

[조던]

감사드립니다. ~^^
많은 도움이 되었습니다.
현재 시장은 작은 호재에도 크게 오르는 풍선시장인 것 같네요.
임상은 이제 시작인데도 불구하고 말이죠.
따라서 주가에 흐름에 따라야 할 것 같네요.

[보타니카]

우와!
연예인한테 답글 받은 느낌이에요!
도움이 되었다니 정말 기뻐요!! ㅎㅎㅎㅎㅎㅎ

메뉴얼 정말 감사드려요! 아무리 공부해보아도 조던님 메뉴얼만큼 손실의 위험성을 줄이고, 장기적으로 투자하게 해주는 방법은 없는 것 같습니다.

[메이저]

코로나19 팬데믹 사태는
딮스테이트들/의료 마피아(빌 게이츠, 닥터 파우치 등)들이 백신 팔아 먹기 위해 의도적으로 뿌린 것입니다.


3월 주식 시장의 대폭락은
3/20일 파생 만기일에 코로나19 바이러스 사태를 불쏘시개감으로 활용하여
만기일에 수십조원의 이익을 갈취하기 위한 글로벌 메이저의 작품인 것이지
그 이상 이하도 아닙니다.

3월 폭락은 일시적인 변동성(잡음)의 일부분일뿐 대세 추세(신호)를 깨트릴 요인은 아니라고 봅니다.


백신 맞으면 안됩니다.
백신은 주사에 의한 살인입니다.
백신속에는 수은, 알루미늄, 포르말린 등이 들어 있어
송과선을 파괴해 치매 등을 일으키는 독극물입니다.

백신의 비리를 철저하게 파헤친
위대한 양심 환경론자인 후나세 슌스케 박사가 쓴
<<백신의 덫>>과

오로지 박사가 쓴
<<백신주의보>>
추천 드립니다.

[아하달한번예쁘네]

1상은 사실 효과가 중점이 아니라 안전성, 최대용량에 초점이 맞춰져있습니다.

[보똥]

좋은정보 감사드립니다~

[쪼코파이]

좋은정보감사합니다. 전문가님들의 이런 분석 아주 유익합니다.

[라니에르]

아 어려워요. 백신, 골아프고,
현재 백신을 만들 나라는 미국밖에 없고, 중국애들은 능력은 없으면 해킹하려고만 하고 있고, 쩝

[Jingu80]

어찌해야할지요 코로나가 갈길을 막네요

[이샘]

감사합니다.

[패트릭]

백신이 실패해도 시장은 또다른 희망의 끈을 어떻게든 붙잡고 갈거라고 봅니다, 모든 참여자들이 결국 자산 상승을 바라고 있기 때문이기도 하겠구요