鉄腕アトムに出てくる「ATLAS」
さて、今回は「ヘルペスワクチンリスト 第6弾！」でございます。
今回、ご紹介するのは、Genocea Biosciences が開発を進めている GEN-003 です！GEN-003は、私がネタ元でお世話になっているフォーラムでもよく取り上げられている
サブユニットワクチンの中でも最有力候補！( ﾟДﾟ)
でして、結構いい成績を残しているのではないかと思っています。ちなみに、GEN-003についての最近の投稿は、こちらで確認できます。
まずは、GEN-003に関する最近の動きをまとめてみると…
- 現在、Phase 2が進行中（おそらくPhase 2a）
- Phase 2の治験では、ヘルペス発症頻度が65％、ウィルスの排出が50％減少した
今回の記事のために、ちょっと最新の情報について調べてみたところ…、
GEN-003を開発しているGenocea BiosciencesでCEO（最高責任者）を務めているChip Clark氏、GEN003の最新情報について語る！
Genocea's Herpes Vaccine Update: An Interview With Chip Clark, CEO
という記事を見つけました！( ｀ー´)ノ
ちなみに…、Genocea自体のホームページは、以下のような感じになっていますね…。
Google Mapで会社の外観を見てみようと思ったんですが、さすが熾烈な戦いを繰り広げているバイオ系の会社ですね！衛星写真で上からの確認はできても、ストリートビューでは全く確認できないようになっているんですね…。何か、競争の熾烈さをかんじてしまいますね… ( 一一)
さてさて、そのGEN-003に関するインタビュー記事なんですが、簡単に内容をまとめてみると、以下のようなポイントをピックアップできると思います…。
- GEN003の最新情報について…
今現在、GEN003はPhase 2bの最終段階にあり、今年の中ぐらいには12か月の追跡結果を公表できるだろう。Phase 2の結果、Phase 3で実施するための適切なワクチン濃度が昭会なったので、2017年末には治験を実施するように計画している。おそらく、治験が完了するまでには2年近くかかるので、2020年にはBLA（Biologics License Application 生物製剤承認申請）に申請し、2021年には承認を得たいと考えている。
- 治験への参加について…
治験の最新情報については、Trial.orgで確認してほしい。
- GEN003は「予防」にも効果があるのか？
GEN003はもともと「治療目的」で開発をしてものであるが、未感染者にも効果はあると考えている。ただ、そのための治験を行う予定は今のところはない。
- GEN003はHSV-1にも効果はあるのか？
GEN003を開発する際に選定された抗体は、HSV1-2の双方に共通性を持つもので、生物学的な見地からすると、HSV2だけでなく、HSV1にも効果があると考えている。Phase 3では、HSV1-2の両方に起因する性器ヘルペス感染者を対象に治験を行いたいと考えている。
- アブユニットワクチンがあまり有効性を示せていない中で、GEN003が有効であるというその理由は？
簡単に言うと、「T細胞の反応を効果的に引き出すための適切な抗体を選別できていないから」ということにつきる。GEN003においては、Genoceaが開発した ATLAS法を約200名の被験者に適用し、HSV2ウィルスに対するT細胞の反応を観察することで、より効果的にその反応を引き出すいくつかの抗体を見い出した。その中でも、強力にT細胞の反応を誘発する2つのタンパク質を基に、このGEN003を開発した。
- GEN003とバルトレックの併用は可能か？
GEN003は性器ヘルペスの再発とウィルスの排出を減少させるが、バルトレックスとの併用をこの好む人も多くいるだろう。いずれ、治験などを実施したいとも考えている。
- Phase 2aの結果はあまり芳しくなかったようだが…
最新の結果を見ると、統計的に有意な効果が確認されており、効果は確実に確認されている。Phase 2の治験結果を見ると、接種後2年間、再発が減少し、ウィルスの排出も77％減少した古都も報告されている。Phase 2bの治験では、6か月目で再発が52％減少したことも報告されている。
内容を見るかぎり、結構ズバズバと聞いているなぁ…、という印象を持ちました…。特に、最後の「Phase 2aの結果はあまり芳しくなかったけど…」というところなんかはスゴイですよね…。日本人だったら、こんな聞き方はあまりしないかもしれませんね… ( 一一)
どうやら、このGEN003の有効性のカギを握るのが…、
Genocea Biosciencesが特許を握っている ATLAS という技術
のようなんですね！
そこで、ATLASについて少し調べてみると、以下のような説明が掲載されておりました。
ATLAS, a first of its kind, proprietary rapid antigen-screening system identifies, via a cellular assay, what the T cells of people who naturally protect themselves against disease do differently than the T cells of those who don’t. In order to detect the most important T cell responses, ATLAS is unbiased: rather than predicting which antigens are meaningful, it instead takes a panoramic snapshot of actual human T cell responses to any possible T cell target in a pathogen or cancer. By associating these individual T cell response signatures with differential clinical outcomes across large cohorts of patients, ATLAS can select the most clinically relevant T cell targets for vaccine and immunotherapy development.
http://www.drug-dev.com/Main/Back-Issues/ANTIGENSCREENING-SYSTEM-Perfecting-the-Promise-of-1127.aspx
う～ん、ちょっとよく分からなかったところも多いのですが（汗）…、
要は、免疫（特にT細胞の反応）には個人差があり、ある抗原に対しよく免疫が働く人もいれば、そうでない人もいいる。どうやら、ATLASは、その個人差を取っ払って、「抗原に対して誰にでも効果のある（＝T細胞の反応を効果的に引き出せる）」抗体タンパク質を探し出す技術
ということになるのかもしれません…。この部分は、ホンマによくわからなかったので、専門家の方がいらっしゃったらコメントをお願いします… m(__)m
実際に治験が進行しているケースは、本当に貴重ですので、是非とも Phase 3でも結果を残して欲しいと思います☆(^^♪
鉄腕アトムで出てくるアトラスは「人間に逆らえる自我＝「オメガ因子」の組み込まれた有色人種型のロボットとして誕生」したわけですが…、このアトラスさんは、性器ヘルペスに苦しむ人たちにとっては大きな希望を与えてくれる技術だと思います！( ｀ー´)ノ
是非、応援していきたいワクチン研究ですね☆
では、また、次回の報告をお楽しみに！( ｀ー´)ノ
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Genocea's Herpes Vaccine Update: An Interview With Chip Clark, CEO
By Josh Bloom — May 26, 2017
The American Council on Science and Health
Chip Clark, Genocea's CEO, kindly agreed to answer my questions about the company's GEN-003 herpes vaccine, and provide an update on the vaccine's progress. I would like to thank Chip for taking a considerable amount of time to speak with me. The interview below should answer some of the many questions that readers have been writing and calling about.
JB: Can you update us on Genocea's current plans and timelines. If all goes well, can you estimate when the Biologics License Application (BLA) might be granted? (1)
CC: Genocea is currently finishing up its Phase II and III? program on GEN-003, and recently had a successful end of Phase II meeting with the FDA. In the middle of the year, we expect to announce the 12-month placebo-controlled clinical results from the Phase IIb trial that uses the Phase III-ready formulation of GEN-003 at the expected Phase III dose. If all continues to go well, Genocea plans to have GEN-003 ready for Phase III by the end of 2017. We expect the clinical trials to take approximately two years from initiation to data and could, therefore, be in a position to file our BLA in 2020, with the potential for approval in 2021.
JB: Is it possible for people to enroll in any of these trials?
CC: At this time, our ongoing Phase II clinical trials are fully enrolled. The next enrollment opportunity will be in our Phase III program, the full details of which will appear on clinicaltrials.gov when the protocol is finalized and the trial(s) open.
JB: People are very interested in 003, both for therapy and prevention. It is, of course, more difficult to run a trial for prevention. Do you plan to do so, and if so, when?
CC: GEN-003 is being developed as an immunotherapy/therapeutic vaccine in patients already infected with HSV. Theoretically, GEN-003 could be used in uninfected patients to help prevent infections, but we have no plans to conduct such a trial before an approval as a therapeutic.
JB: HSV-1 is now the most common cause of genital herpes in young women. Rumor has it that 003 is not expected to work against HSV-1. Is this correct? If so, do you think this will be problematic since so many genital herpes cases are caused by HSV-1?
CC: This is not correct. The antigens identified and chosen for GEN-003 are highly conserved across HSV types 1 and 2. Thus far, we have only studied GEN-003 in patients with HSV-2, but, given the biology, we believe that GEN-003 could work in patients with either HSV-1 or 2. We intend to include both HSV-2 and HSV-1 patients in the Phase 3 program and to seek approval for the treatment of genital herpes infections irrespective of serotype.
JB: Subunit (synthetic) vaccines have a poor track record. Why do you expect 003 to work when many others have failed?
CC: Simply put, we think that other vaccines have failed because they have used the wrong antigens, and have therefore failed to effectively direct T cell responses to attack the virus.
We selected the GEN-003 antigens using our ATLAS (2) platform, which comprehensively profiled the T cell immune responses of approximately 200 people to HSV-2 and associated those T cell response signatures with clinical outcomes. We found that a handful of HSV-2 antigens were associated with protective T cell responses and, from that small number of antigen candidates, we selected the two protein components of our vaccine.
We have shown now in three trials that GEN-003 reduces the genital lesion rate, reduces viral shedding, and drives strong and antigen-specific T and B cell responses.
JB: Is 003 intended to be a stand-alone treatment, or will it be necessary to also use an antiviral such as Valtrex.
A: We have recently shown that GEN-003 can reduce the genital lesion rate vs. placebo by 50% at six months post-dosing.Whether a patient chooses to use GEN-003 alone or together with an antiviral drug may ultimately come down to patient choice. We know from our market research that patients hate taking a pill every day and for this reason, about two-thirds of patients who take antivirals only take them when they have a lesion recurrence.
This represents a significant unmet medical need because taking antivirals in this way does nothing to reduce the frequency of recurrences and provides no reduction in viral shedding when they are not taking the pills (increasing transmission risk). We do plan to study GEN-003 in combination with daily Valtrex in the future to see if there is an additive benefit of taking both together.
Our market research suggests that the prospect of GEN-003’s significant and sustained efficacy from a single course of injections would cause many patients currently taking antivirals to switch. You can also imagine a scenario where GEN-003 could be the cornerstone therapy for a patient, who could preserve antiviral use to treat outbreaks if they occur.
JB: Do you expect to see an enhanced immune response during dose finding Phase IIb studies? Do you expect the Phase IIb results to be superior to those of Phase IIa?
A: We have already shown consistent clinical and virologic efficacy and immune response results between our prior Phase II trial and our ongoing Phase IIb trial.
JB: Can you briefly compare 003 with vaccines from Theravax, NanoBio, and U Penn, especially with regard to immune response, efficacy (when available), safety, and your estimate of the chance of success of all four.
A: No. Our point of unique differentiation is how we selected the antigens for GEN-003 using ATLAS. Without ATLAS, we believe you are guessing.
JB: I have called your Phase IIa data unimpressive. Is this fair? If not, why?
A: No. I don't think this is a fair statement. We have now shown statistically significant clinical efficacy and viral shedding results across three separate clinical trials. Our most recent data – here – from the previous Phase II trial shows that we continue to reduce genital lesion rate and viral shedding rate vs. baseline by up to 77% for at least two years after dosing. Moreover, in our ongoing Phase IIb trial, we announced median genital lesion rate reductions vs. placebo of 52% over the six-month period post dosing (this is expected to be our primary Phase III endpoint).
Our market research (involving hundreds of patients and physicians) has been conducted on the basis of our actual clinical trial results, not an aspirational profile, and consistently supports our assertion that GEN-003’s demonstrated levels of efficacy in its trials to date are highly attractive to patients and physicians who have been starved of innovation and new treatments for this serious disease for more than 20 years.
JB: Are other papers about 003 being written? If so, when do you think they might be published?
A: We have an active publication calendar. You can view previous publications on our website at www.genocea.com. We’ve had a number of abstracts just accepted to the IHW meeting this summer in Belgium as posters and one oral presentation, and we also expect to be presenting data at the IDWeek conference in October in San Diego. We have manuscript drafts in the works as well, and plan to submit these to peer-reviewed journals for publication when completed.
Notes:
(1) A Biologics License Application (BLA) is like the New Drug Application (NDA) that must be granted by the FDA for approval. The difference is that the BLA includes biologics, such as vaccines, and antibodies, while the NDA is for small molecule drugs (pills).
(2) ATLAS is Genocea's proprietary rapid antigen identification screening system that is designed to find targets of protective T cell responses.
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