血友病基因疗法商业化进程中的成长阵痛

四分之一的患者从未开始他们被开具的治疗方案。这意味着数百万人错过了药物治疗的益处。Timely由医生推荐。First是一个端到端的互动平台，通过个性化短信提升认知度、增加可及性并促进用药依从性。凭借85%的互动率推动处方量增长10%，Timely确能带来实效。

One in four patients never start the therapy they're prescribed. That's millions missing out on the benefits of your medication. Timely by Doctor. First is an end to end engagement platform that delivers personalized SMS messages to boost awareness, increase access, and drive adherence. With an eighty five percent engagement rate driving up to 10% more prescription fills, Timely delivers results.

这就是为什么前20大制药公司中有16家选择信任我们。访问timelyhealth.com/fierce了解Timely如何为您服务。

That's why 16 of the top 20 pharmaceutical companies trust us. Visit timelyhealth.com/fierce to see what timely can do for you.

您正在收听由Fierce Pharma和Fierce Biotech联合制作的《头条聚焦》节目。我是主持人艾拉·埃里森。基因疗法长期以来承诺将彻底改变血友病治疗，有望以一次性疗法替代终身输注。但随着首批产品上市，现实情况却更为复杂。今年早些时候，辉瑞的血友病B基因疗法上市不足一年便撤市，原因是医患关注度不足。

You're listening to the top line brought to you by Fierce Pharma and Fierce Biotech. I'm your host, Ayla Ellison. Gene therapy has long promised to transform the treatment of hemophilia, offering the possibility of a one time therapy in place of lifelong infusions. But as the first products reach the market, the reality is proving more complicated. Earlier this year, Pfizer withdrew its hemophilia B gene therapy after less than a year on the market, citing limited patient and physician interest.

这一举措引发疑问：挑战究竟在于科学本身、经济因素还是治疗推广方式？为厘清这些问题，Fierce Pharma记者佐伊·贝克尔采访了世界血友病联盟医学副总裁格伦·皮尔斯博士。他数十年来致力于推动血友病研究与治疗。他们探讨了基因疗法的现状、采用速度低于预期的原因，以及如何让这些疗法惠及所需患者。

The move raised questions about whether the challenges lie with the science, the economics, or the way the treatments are being introduced. To help sort through those questions, Fierce Pharma's Zoe Becker spoke with Doctor. Glenn Pierce, vice president of medical at the World Federation of Hemophilia. He spent decades working to advance hemophilia research and care. They discuss the current state of gene therapy, why adoption has been slower than expected, and what needs to happen for these therapies to reach patients who need them.

让我们深入探讨。

Let's get into it.

感谢您今天接受采访，格伦。

Thank you for joining me today, Glenn.

不客气。谢谢邀请我，

You're welcome. Thanks for having me, So

血友病基因治疗领域仍处于起步阶段，在商业化进程中面临诸多挑战。例如，辉瑞公司在今年二月停售了上市约十个月的B型血友病基因疗法Beqvez。当时该公司将此归因于患者及医生对血友病基因疗法兴趣有限。虽然Beqvez上市后确实没有商业患者使用，但辉瑞这一声明本身存在问题，因其未能全面反映真实情况。对吗？

the hemophilia gene therapy space is still new and facing challenges as it ramps up commercially. Pfizer, for example, in February discontinued a hemophilia b gene therapy that it marketed for about ten months called Beckbez. At the time, the company attributed the move to limited interests that patients and their doctors have shown in hemophilia gene therapies. So while it's true that BeckVest did have no commercial patients since launch, this statement from Pfizer in itself is problematic as it doesn't present an entirely accurate picture. Correct?

确实如此，Zoe。辉瑞向日本行业期刊发表了这番言论，但最终被更广泛的生物技术行业受众所关注。由于这个说法很抓人眼球——'患者和医生对血友病基因治疗不感兴趣'——引发了大量媒体报道。但问题在于：第一，这并不符合事实。

That's true, Zoe. Pfizer made that quote and gave it to a Japanese industry journal, but it wound up getting picked up that they assumed it would by the wider biotech industry audience. And so it got quite a bit of press because it's a catchy quote. Oh, patients and doctors aren't interested in gene therapy and in hemophilia. Unfortunately, number one, it's not true.

第二，评估任何新产品的收益风险比至关重要。需要审视临床试验数据，比较其与现有疗法（如血友病治疗方案）的优劣，以及与其他基因疗法的风险差异。目前B型血友病（两种血友病之一）还有另一款获批基因疗法。或许我该先说明：血友病分为A型（凝血因子VIII缺乏）和B型（凝血因子IX缺乏）。

And number two, it's important to look at the benefits and risks of any new product that comes out. Look at the clinical trial data and understand how does it compare to other products that are available to, for instance, people with hemophilia and how do the risks compare to the risks of other gene therapies that are also In this case, there's one other gene therapy that's been approved for hemophilia B which is one of the two hemophilias. Maybe I should back up and just say there's hemophilia A and hemophilia B. Hemophilia A is a deficiency of coagulation factor VIII. Hemophilia B is a deficiency of coagulation factor IX.

两者表型相同，未经治疗都会导致不受控出血。过去六十年来治疗方案不断演进，近十年基因疗法临床试验趋于成熟，目前已获批一款IX因子和一款VIII因子基因疗法。CSL公司分销的另一款IX因子基因疗法与辉瑞停产的非常相似，但在疗效和安全性数据上略有差异。

They both have the same phenotype, so they both result in uncontrolled bleeding if not treated. And over the past sixty years or so, a number of treatments have come along and there's been a lot of evolution in treatments. Over these past ten years, gene therapy clinical trials have matured sufficiently to result in the approval of now one factor nine and one factor eight gene therapy for patients with hemophilia. The other factor nine gene therapy, which is distributed by CSL, is very similar to the one that Pfizer has discontinued. But the data both on efficacy and safety are a little bit different.

CSL产品的疗效更高且安全性更优。企业必须评估这些竞争要素：我们的产品是否能与已上市一两年的竞品抗衡？从这个角度看，辉瑞将产品竞争力不足归咎于血友病群体，对这个出血性疾病群体有失公允。我认为辉瑞高管可能判定该产品缺乏竞争力才决定退市。

Efficacy is higher in the CSL product and the safety is better in the CSL product. And so those are competitive features that companies have to decide. Are we competitive with the existing product that's already been on the market for one or two years or are we not? And so in that sense, I think Pfizer did a disservice to the hemophilia bleeding disorders community by blaming the community for what may not be a competitive product. And I think the assumption that Pfizer executives made a decision that this was not a competitive product and perhaps it should be pulled from the market.

真有意思，这里涉及很多深层问题。您在六月的论文中与合著者反驳了'兴趣缺失论'，并探讨了'为何血友病基因疗法采用率低于预期'。Glenn，您对这个问题的总结性回答是什么？

Fascinating. There's a lot to get into there. And you discussed some of this in a June paper in which you and some coauthors countered that notion about the lack of interest and sought to answer the question, why is uptake of gene therapy and hemophilia less than expected? So, Glenn, what would be your summed up answer to that question?

目前上市的两款基因疗法——CSL的IX因子产品和BioMarin的VIII因子产品——都经历了长期临床试验，近两年获FDA和EMA批准。它们并非完美，其中一款可能更不完美。基因治疗的概念看似简单却充满复杂性：用新基因替换缺陷基因的理念自1970-1971年以来就备受科学界关注。

The two gene therapies that are available, the CSL product for factor nine and then a BioMarin product for factor eight have come through a long series of clinical trials and were FDA and EMA approved over these past couple of years. They're not perfect. And one is perhaps a little less perfect than the other. The concept of doing gene therapy is a simple one, but is fraught with complexities. So the idea of putting a new gene in to replace a gene that's defective makes good sense and is something that the scientific community has been interested in since 1970, 1971.

但实际操作过程中却遭遇了一个又一个障碍。距离最初概念提出已过去55年，我们却仍只是触及单基因疾病和有效基因疗法的表面。基因疗法的核心理念就是治愈疾病。通过用正常基因替换缺陷基因来治愈疾病——或者说理应如此。以CSL公司及其九因子产品为例，本质上就是在实现这一目标。

But the actual process of doing it has encountered hurdle after hurdle. And so here we are fifty five years after that initial concept was developed and we're still just just touching the surface of getting to monogenic diseases and having good effective gene therapies. The whole concept of gene therapy is to cure the disease. And so replacing a defect in gene with an existing one cures the disease or should cure the disease. For the case of CSL and their factor nine product, it is essentially doing that.

这类结论的得出需要时间。但我们现有患者使用该产品变体已长达十三、十四年，他们体内九因子表达稳定。CSL这款产品本身能提供约37%的九因子活性，使患者活动能力接近正常水平，这相当不错。不过在这个水平上，患者仍会出现出血现象。

It's taken time to make that kind of determination. But we've got patients that are out now thirteen, fourteen years with variations on a theme of that product and they have stable factor nine expression. The actual product itself from CSL, that product is giving about 37% factor IX activity. And that puts patients into the near normal range of activity, which is pretty good. At that level, those patients will bleed.

这仅是平均值，意味着既有低于此值的患者，也有高于此值的患者。但总体而言，B型血友病患者的出血事件和出血风险已大幅降低，且效果持久。八因子产品能使患者维持在20%-40%水平，但部分患者会逐渐丧失部分活性——这使得该疗法对至少部分临床研究患者无法产生永久效果，因而相较九因子产品，其获益风险比有所不同。

Now that's an average and so that means there are some patients below that and there are some patients above that. But by and large, it is greatly diminished bleeding episodes and the risk of bleeding in individuals with hemophilia B and it appears to be durable. Factor VIII is putting patients into the twenty to forty percent range, but a number of patients are losing some activity along the way. And so that's been a little bit more problematic in that it's not a permanent effect for at least a number of patients that have been studied clinically. So for that reason, it's a different sort of a benefit risk ratio compared to the factor nine product.

必须评估患者现有可用的治疗方案，以及这些方案能否抵消基因疗法带来的收益与风险。

One has to look at the products that are available to those patients and whether or not those products would offset the benefits that one sees with the gene therapy, some of the risks that one sees from the gene therapy.

有意思。我明白了。正如你所说，基因疗法仍属新兴领域，而现有市售治疗方案虽非治愈性但应用广泛。是否存在某些对这种方法持保留态度或普遍怀疑的群体？

Interesting. I see. You know, as you're saying, therapy being pretty new still and obviously there are those marketed treatments that do exist, not curative, but do get a lot of use. Is there some pockets of hesitancy or maybe just skepticism in general towards the approach?

血友病治疗领域近年来涌现了大量新疗法，这是药物研发的基本规律——你不是为一期临床试验时的治疗现状研发药物，而是为七到十年后完成临床试验时的治疗需求研发。遗憾的是基因疗法领域确实出现了重大技术突破：我们现在有了A型血友病治疗药物，一种双特异性抗体可模拟八因子功能，每月仅需皮下注射一次（非静脉注射）就能提供出色的出血防护。

I think that the hemophilia community has been blessed with a plethora of new therapies that have come out and that's one of the principles of drug development. One doesn't develop a drug for the therapies that are present when you enter a phase one study. One develops a drug for the therapies that will be present seven to ten years later when you come out of your clinical trials. And unfortunately for gene therapy some real technical advances have come along. We now have a hemophilia A, we have a bispecific antibody that can mimic the functions of factor VIII and be taken as little as once a month to give very good protection from bleeding and it's given subcutaneously, not intravenously.

现有再平衡制剂能重新调节凝血系统——当缺乏促凝血因子的血友病患者减少抑制凝血系统的抗凝因子时，就能恢复部分凝血功能。去年刚上市了三种此类制剂。此外还有超长半衰期八因子产品，能让患者每周保持四天正常水平，周末时仍维持10%-15%的八因子活性，使这些患者几乎不会发生过度出血。

We now have some rebalancing agents that are available that rebalance the coagulation system so that a person with hemophilia, which is deficient in procoagulants, if they lose some of their anticoagulants that keep the coagulation system in check, then they can restore some coagulation, some hemostasis. And three of those agents had just come out in this past year. And then there's an ultra high half life factor VIII that's come out that keeps patients normal for about four days out of the week. And then they finish the week at about 10 to 15% factor VIII. That results in very little excess bleeding from those patients.

最初在血友病中开展第八因子、第九因子许可研究时，所有这些都还只是梦想，但如今已成为现实。这是患者必须与家人、医疗服务提供者共同参与的共享决策过程，以确定现阶段最适合我的治疗方案。对部分患者而言，基因治疗将是选择——无论是针对第九因子还是第八因子。第九因子患者可能会说：'我愿意赌一把能获得好结果，如果达到足够高的水平，甚至可能实现看似持久的治愈。'而第八因子患者则需要决定：'我接受治疗，可能获得显著效果，但也可能在过程中丧失部分活性或效果不佳。'

So all of these things were a dream when the initial factor eight, factor nine licensure studies started in hemophilia, but they've become real. And that's part of the shared decision making, informed decision making process that patients have to go through with their families, with their providers, their health care providers in order to determine what's right for me at this point in time. For some patients it will be gene therapy whether it's factor nine or factor eight. For factor nine they'll say I want to take the chance that I'm going to get a good result and really have what looks to be like a durable cure if I have a sufficiently high level. For factor VIII patients, patients need to decide, I'll take this, I may get a great result, but I also may lose some activity along the way or not get a very good result.

我愿意承担这个风险。这是每个人需要自主做出的重要决定。当前所有应用的基因疗法——所有AV载体基因疗法的共同特点是'一锤定音'。无论效果好坏，你都只能接受结果，因为我们会产生高滴度的AAV抗体。AAV即腺相关病毒。

I'm willing to take that risk. That's an important decision that each individual needs to make personally. And the issue with all the gene therapy that's being used is that the issue with all AV gene therapy that's being used is that it's one and done. So good result, bad result, you're stuck with it because we make very high titer antibodies to the AAV. AAV is adeno associated virus.

这是一种能感染人体但不会造成伤害的良性病毒。接受基因治疗的患者，其抗AAV抗体的滴度将维持数十年。所以这就是关键——他们只有一次机会，必须基于这个前提做出决定。

It's a benign virus that can infect us but not cause any damage. And for patients who have received the gene therapy, their titers of the anti AAV antibodies will last for decades. So this is it. This is their one chance, and they need to make the decision based upon that.

当然，高昂的价格标签是这个决策的另一大考量因素。Hemgenix曾以350万美元的价格一度成为全球最贵疗法，Beckba上市时定价也与之相当。您与世界血友病联盟合作推动全球治疗可及性，但单是美国就存在如此多价格门槛等障碍，我们还能采取哪些措施来改善全球可及性？

And of course, another huge part of that decision would be the high price tag. I mean, Hemgenx was the world's most expensive therapy for a while at $3,500,000, and Beckba's matched as well when it was on the market. You work with the World Federation of Hemophilia to prioritize global access to these treatments. But if there are so many barriers to access such as these high price tags in The US alone, what steps can we take to improve global access as well?

佐伊，关于350万美元定价有个有趣现象：在美国这实际具有成本效益。普通B型血友病成人患者使用长效第九因子产品进行预防治疗时，根据体重不同年治疗费可达6,071万美元。因此可见在五到七年内就能收回350万的治疗成本，之后基本就是净收益。问题在于保险公司需要一次性巨额支出，而美国实行的是患者流动保险制度。

The interesting thing Zoe about the $3,500,000 price tag is that it's cost effective in The United States. The average individual adult with hemophilia B is on prophylactic therapy with extended half life factor nine products and they're spending $607,100,000 dollars a year depending upon their weight for their therapy. And so you can see that in five, six, seven years, one will recapture the cost of 3,500,000.0 and then everything after that is basically a freebie. The issue here is that it's a huge outlay for an insurance company to do all at once. And in The United States is patient shift insurance.

这与世界上多数国家不同——那些国家的政府承担医保且保障关系固定。在这里，如果患者更换保险公司，新公司就能免去每年60万美元的支出负担，而原公司已承担了这部分成本。这些变量都是我们在考量高价产品时需要面对的。

And so it's not like you're living in a country, like most countries in the world, where the government pays your insurance and you don't shift governance. Your government insurance is your government insurance. Here, if a patient switches insurance, then the next insurance company gets the benefit of not having to spend $600,000 a year on that patient. But the first insurance company has already eaten that cost. And so those are some of the variables that are occurring as we think about these very high priced products.

但通过系统运作，我知道Hemgenix和定价稍低的Roctavian都在持续收治患者。从ICER数据看，它们当前定价具有成本效益。但对世界其他地区未必如此——Roctavian在德国、意大利等国家都有深度折扣。

But working through the system, I do know that Hemgenics is continuing to gather patients and so is Roctavian, which is priced somewhat lower. And so if one looks at the ICER data, one can see that they're cost effective at the prices that they're at. But for the rest of the world, that's not necessarily the case. Roctavian is deeply discounted in the other countries that it's in. It's also in Germany and Italy.

在这些国家，政府承担Roctavian治疗费用的压力相对较小。虽然我不清楚其他国家在血友病基因治疗上的具体费用差异，但大多数国家每年不会为常规疗法和工厂产品更换支付60万美元——只有美国在承担如此高昂的费用。这需要制造商予以充分考虑。当然，若审视实际生产成本，制造商必然不愿公开这些数据。

And in those countries, then that cost is a bit more manageable to those governments to be able to provide for Roctavian. I don't know the cost differentials with other countries for hemogenics, but other countries by and large don't pay $600,000 a year for regular therapy, factory product replacement. Only The United States is paying that kind of money. So that needs to be taken into account by the manufacturers. If we look at the actual cost of production, of course, the manufacturers aren't going to be willing to release those costs.

但我们从整个相关制造工艺开发、灌装封口及配套质量控制流程可以估算。根据圣裘德儿童研究医院十多年来生产血友病AAV载体的经验，包含患者管理在内的五年综合成本约为8.7万美元。这让我们能更理性看待：基因治疗生产成本虽高，但8.7万与350万有着天壤之别。

But we know based upon the production of the all of the associated manufacturing process development, finish and fill, quality control that's associated with it. We know from the work that St. Jude has done where they have been manufacturing AAV for hemophilia for over a decade, the all in costs for five years, including patient management, are about $87,000. And so that gives you a little appreciation. Yes, gene therapy is expensive to produce, but $87,000 is a far cry from 3,500,000.0.

尽管制造商需要收回研发成本，并满足'以盈补亏'的商业模式要求（包括股东回报），但这套体系对全球85%人口毫无助益。基于收入划分：美国、加拿大、西欧和日本等高收入国家之外——

And while the manufacturers need to recoup their R and D costs and the associated pay it forward kind of prospects that are required, paying the shareholders as well. This is not of benefit to 85% of the world. 85% of the world has almost no access at all to therapy. We break things down on the basis of incomes. And so we have high income countries like The US, Canada, Western Europe, Japan.

还有巴西等高上中等收入国家、中下等收入国家，以及低收入国家。全球多数人口集中在中下等和低收入国家，前者尚能获得少量产品，后者几乎完全空白——这几乎占世界人口半数。

We have high upper middle income countries, countries like Brazil. We have lower middle income countries and then we have low income countries. And the majority of the world sits in low middle income and low income countries. Low middle income countries have a little bit of product, but low income countries have almost none. And that's almost half the world.

因此在资本主义体系下，向这些地区推广基因治疗并不现实。唯有与慈善组织建立联合项目，才可能为高发病率、高死亡率地区创造真正独特的解决方案。

And so the idea of bringing gene therapy there is not realistic in a capitalistic kind of a system. In joint ventures with philanthropy organizations, then we may be talking about something that could be truly unique for the rest of the world that has high morbidity and high mortality.

你如何看待BioMarin将Roctavian商业布局限定在三个高收入国家？应该是美国、意大利和法国吧？

What do you make of BioMarin's decision to limit Roctavian's commercial footprint to three those are high income Correct? I think it's The US, Italy, and France?

还有德国。他们这个决策主要基于对产品市场接受度的预判。如我所述，其产品存在持久性疑问，且部分患者出现不明临床意义的肝酶升高现象。因此他们正集中精力在这三个国家建立产品基础。

Germany. Germany. Well, I think they made a decision largely based upon their perceived views of the uptake of their product. As I mentioned, there are some durability questions with their product, and a number of patients had high liver enzyme levels, higher liver enzyme levels with their product that are of unclear significance. And so they're really focusing on these three countries to establish the product.

我推测如果该产品继续渗透进这些国家，他们会扩大其应用范围。

And I assume that if the product continues to penetrate into those countries, they'll expand it.

几个月前，世界血友病联合会和其他一些国际组织在被称为血友病治疗关键节点的时期发布了紧急行动呼吁。能否谈谈这一背景情况，为何现在是关键节点？

Well, a few months ago, the World Federation of Hemophilia and some other global groups issued an urgent call to action during what was described as a critical juncture in hemophilia treatment. Tell me a little bit about the context of that and why is now a critical juncture?

我们必须将生活在美国、加拿大等高收入国家的患者与低收入国家的患者区分开来。过去十一年间，我们见证了众多长效半衰期产品和再平衡剂的研发与获批。虽然这些是有效疗法，但并非疾病根治手段。塞德里克·赫尔曼医生和我讨论过一个概念——

We have to separate out the patients that are living in The US, Canada, high income countries from the patients that are in lower income countries. We, over the past eleven years, have seen a huge number. All of the extended half life products, all of the rebalancing agents have been developed and have been approved in these eleven years. While they are effective treatments, those aren't cures for the disease. There's a concept that Doctor.

叫做'无血友病心态'，即真正摆脱血友病且无需终日挂念的状态——这正是重症血友病患者的日常。无论是上下楼梯还是徒步，任何细微的关节扭动都可能在缺乏保护时导致出血。尽管防护措施不断完善，但这仍非根治。患者需定期接受治疗，因此我们不应将第一代基因疗法视为疾病的终极解决方案。

Cedric Herman's and I have talked about called the hemophilia free mind, which is really being without hemophilia and not thinking about it 24 a day, seven days a week, which is what an individual with severe hemophilia does. As they go through the day, as they go up a set of stairs or down a set of stairs or take a hike, Any imperceptible twists or turns of their ankles or their knees could result in bleeding if they're not protected. And so while protection is continuing to increase for these patients, it's still not a cure. They have to take treatments on a regular basis. So we don't want to be left with these first generation gene therapies as the ultimate for curing the disease.

首先，ROCTAVIAN无法治愈部分患者，因为他们中途会丧失活性或初始活性不足。其次，对Hemogenis而言，这是优秀的第一代疗法，但不能用于儿童治疗，也无法适用于已接触高剂量AAV或具有高AAV抗体滴度的个体。当前AAV基因疗法存在局限性，这正是我们需要持续创新的原因。我们可以在AAV基础上改进递送系统，或通过基因编辑将凝血因子VIII或IX插入患者基因组——若证实安全，儿童也能因此获益。

First of all, ROCTAVIAN can't cure a number of patients because they lose activity along the way or don't have a high enough activity to start with. And secondly, for hemogenics, it's a great first generation therapy but it can't treat children and it can't treat individuals who already have been exposed to high levels of AAV or have high levels of AAV antibody titers. And so there are limitations with the current AAV gene therapies, which is why we need to continue innovation. We can continue that innovation along the lines of AAV and improve the delivery with AAV. We can improve the delivery by using gene editing to actually insert the factor VIII or factor IX into the genome of patients, so that children could be treated in that case, assuming that it's safe.

或者我们可以转向非AAV载体系统，如非病毒系统或其他病毒载体。印度著名国际医师拉克萨里·瓦斯塔瓦曾使用慢病毒载体将凝血八因子基因直接递送至血友病患者染色体中。在其最新实验中，患者八因子水平已恢复至正常范围，且预期这些患者将获得持久治愈，因为基因已整合入其基因组。可见替代方案确实存在。

Or we could move away from AAV to other vector delivery systems, either non viral systems or even other viruses. Some work was done in India by Laxari Vastava, a well known international physician, using lentiviral vector to deliver the factor eight gene directly into the chromosomes of individuals with hemophilia there. And in his latest iteration, he got patients into the normal range with factor eight. And there's every expectation those patients have a durable cure because the gene's been placed into their genomes. So there are alternatives.

我们希望所有这些替代方案能持续发展，尤其造福八因子缺乏症患者，同时让九因子疗法也能惠及儿童。其他出血性疾病如血管性血友病——其实是最常见的出血性疾病（尽管多数患者症状轻微）——仍缺乏治疗手段。通过率先开发八因子相关技术，我们能为治疗重症血管性血友病铺平道路。因此，持续研发技术以实现所有出血性疾病的根治疗法具有重大意义。

We want to see all these alternatives continue to be developed for the benefit, especially if people with factor eight deficiency, but also for factor nine to continue to get into children. There's also other bleeding disorders that have not been addressed by Willebrand disease, which is actually the most common bleeding disorder, although many people have only mild symptoms. But for the people that have severe symptoms, there's very little available to them. And developing the technologies, pioneering them with factor VIII, for instance, can lead the way to being able to do the same thing with von Willebrand factor and treat patients with severe von Willebrand disease as well. So there's a lot of incentive to want to continue to develop the technologies to get to curative therapies for all of the bleeding disorders.

哇，看起来未来有很多创新的空间。

Wow, looks like there's room for a lot of innovations on the horizon.

确实如此。我们只是需要确保不让世界其他地区掉队。这是我最大的担忧之一。这些技术中，许多是过去十一年间投入使用的单克隆抗体技术，它们相对便宜，我们正将其推广到低收入国家。

There is. We just need to be able to not leave the rest of the world behind. And that's one of my biggest concerns. With these technologies, many of the technologies are monoclonal antibody paste that have come into use over the past eleven years. Those are relatively inexpensive and we translate that into the lower income countries.

到目前为止，除了一些制造商通过人道主义援助提供帮助外，其他制造商一直不愿降价以适应这些政府能承受的价格水平。

So far manufacturers had been resistant other than some of them helping through some humanitarian aid work. But they've been resistant to reduce the prices to be commensurate with the kinds of prices those governments can afford.

好的，格伦，非常感谢你今天抽时间。

Well, thank you so much for the time today, Glenn.

不客气。谢谢你给我机会谈论我最喜欢的话题。

You're welcome. Thanks for giving me an opportunity to talk about my favorite subject.

以上就是本期的主要内容。我是主持人艾拉·埃里森。您可以在我们的节目笔记中了解更多关于这个话题的信息，请访问fiercepharma.com，查找播客。以上就是本期节目的全部内容。

That's it for the top line. I'm your host, Ayla Ellison. You can find out more about this topic in our show notes at fiercepharma.com. Look for podcasts. And that's the bottom line from the top line.