制药业的未来在于：让已有的好药变得效力更强？

    新药品的研发成本正在继续飙升。根据来自塔夫茨药物开发研究中心的数据，开发、测试一款新药并通过监管机构的批准，可能要耗费制药公司25亿美元以上，比10年前翻了一倍还多——2003年，制药公司将新药推向市场上的费用约为8.02亿美元（按2013年购买力计算约为10.4亿美元）。

    一些制药公司和生物科技公司都想知道怎样才能加大投入产出比，而其中的一种方法就是让现有的药品，也就是那些已经经过测试和认证的知名药品，变得更加有效。

    彭博社智库生物科技分析师阿斯卡•古纳瓦迪尼认为：“随着市面上的仿制药越来越多，这种发展趋势是很自然的。各大公司都在研究新的给药方法，或是将现有药品以新的方法进行组合。这是一种可行的办法。”

    一些知名药企已经进入这个领域，其中包括阿特维斯和梯瓦制药等公司。其他规模较小的药企也在寻求能够颠覆游戏规则的创新，比如MannKind公司研发的吸入式胰岛素Afrezza，以及Heron Therapeutic公司极具科技含量的高分子聚合物给药平台Biochronomer，它可以让现有注射类药物的药效更加持久。

    古纳瓦迪尼表示：“如果采用一种已经通过认证的药物，就相当于削减了认证过程。这种方式的风险更低，因为美国食品药品监管局（FDA）很喜欢这种做法。”

    在费城郊外，一家名叫OptiNose的生物科技公司就在深耕这一领域。该公司发明了一款相对来说并不是特别高科技的设备。这款设备可以将药物送到它需要去的地方，进而有望改变传统的治疗方式。

    这款塑料设备利用人类的自然呼吸来关闭鼻腔，然后将药物送至鼻腔深处。当你通过嘴巴大力呼气时，软腭会关闭通向鼻腔的气道，这也就是为什么你无法同时用嘴巴和鼻子大力吹气的原因。它的作用其实就相当于封闭鼻腔，使药物可以在那个封闭空间进行循环，同时你的呼吸会将药物直接送至鼻窦。

    OptiNose正在与Avanir公司进行合作，而这款产品的首个用途（治疗偏头痛）有望很快获得FDA的批准。临床研究显示，与口服药物相比，这种靠呼吸给药的设备使药物进入血液的速度更快，同时需要的药物剂量也更小。它的药效几乎像注射一样快，但病人无需挨上一针。

    开发这种新型给药机制的成本大约只有3000万到5000万美元。这还包括正在接受FDA审核的另一项针对慢性鼻窦炎的研发费用。

    Optinose公司CEO彼得•米勒指出：“药品开发最难的部分是，很多好药由于安全问题而无法面市。在药品开发的早期阶段，大家都知道出现了非常好的药效，他们才会开始进行动物实验并寻找副作用。但由于我们采用的药品已经在人身上用过了，特别是我们的头两款药品已经被人使用过数百万次了，因此我们的开发风险和监管风险与合成一种新药相比，完全不在一个级数上。”

    由于使用的剂量更少、给药更快、或提高了药效，这些更好的给药手段不仅降低了研发成本、优化了药品利用率，还帮助制药公司延长了一些专利原本要过期的药品的专利保护权。药效的改善和专利权的更新，赋予了制药公司更大的定价权（不过古纳瓦迪尼指出，这种定价权显然还是比不上开发一款全新的药物）。

    尽管这种给药机制解决的只是一种病症，但它依然面临非常巨大的商机。以OptiNose为例，该设备目前也被用来临疗鼻息肉和鼻窦炎，采用的药物是广为人知的氟替卡松。OptiNose公司表示，它有可能打开一个市值至少在15亿美元的市场。

    它还有着更大的前景：鼻腔是大脑与外部世界唯一接触的直接接触区域。该公司表示，未来OptiNose有可能通过鼻腔给药，在治疗自闭症和阿尔茨海默症等中枢神经系统疾病上达到更好的效果。

    当然，要在临床测试中确认这些事，还有很长的一段路要走。此外，新的给药方法仍然无法超越现有药物和人体的极限。尽管如此，这种技术进步正在进入市场，而且有望显著提升现有好药的治疗效果。（财富中文网）

    译者：朴成奎

    审校：任文科

    The cost of developing new drugs continues to soar. These days, drug developers can expect to shell out more than $2.5 billion to create a medicine, test it, and win regulatory approvals, according to data from the Tufts Center for the Study of Drug Development. That’s more than double what it cost just over a decade ago: In 2003, bringing a new drug to market required about $802 million (that’s $1.04 billion in 2013 dollars).

    Some pharmaceutical and biotech companies are asking how this can be done better. One way to do it is to make existing therapies — medicines that are known, tested and approved — even more effective.

    “It’s a natural progression as there’s more generics out there,” said AsthikaGoonewardene, a biotech analyst with Bloomberg Intelligence. “Companies have been working on different delivery methods, or combining different drugs in new ways, for awhile now. It’s a viable way to do it.”

    Some big name guys have entered the field, including Actavis ACT 0.55% andTeva Pharmaceuticals TEVA 0.94% . Other smaller guys are looking at game-changing innovations, including MannKind’s MNKD -4.40% inhaled insulin Afrezza, or Heron Therapeutic’s HRTX high-tech Biochronomer, a polymer-based drug delivery platform that makes existing injectable drugs longer lasting.

    “By taking a drug that’s already approved, you’re trimming down the approval process,” says Goonewardene. “It’s a lower risk product because the FDA’s already liked it.”

    OptiNose, a biotech company outside of Philadelphia, has focused its efforts in this field. The company has developed a relatively lo-fi device that has the potential to transform treatments for problematic conditions simply by getting the medicine where it needs to go.

    The plastic device uses the body’s natural breath to close off the nasal cavity and send drug very deep into the nose. It takes advantage of the fact that when you blow hard out of your mouth, the soft palate closes off airway access to your sinuses. It’s why you can’t blow hard out of your mouth and nostrils at the same time. That essentially seals off the nasal cavity allowing the drug to circulate in that closed-off area while your breath sends the drug high into the sinuses.

    OptiNose, in partnership with Avanir, is nearing the Food and Drug Administration’s approval for its first use: to treat migraines. Clinical studies have shown that the breath-powered device gets the drug into a patient’s blood faster than oral medicine, while requiring a smaller dosage. It’s almost as fast as an injectable, but without the need to use a needle.

    The cost for developing this new delivery mechanism? About $30 million to $50 million. That sum includes a second treatment for chronic sinusitis under current FDA review.

    “The hard part of drug development is that so many good drugs fail because of safety issues, so there’s known to be really good activity in the early development stages, then they put them into animals and find side effects,” says Optinose CEO Peter Miller. “Because we’re taking drugs that have been in humans, in the case of our first two drugs, they’ve been used millions of times by people, our safety risks and therefore development and regulatory risks are a completely different magnitude than a new molecular entity.”

    Better delivery not only lowers the cost of development and optimizes drugs — by using less, speeding delivery or improving results — it also allows drugmakers to extend patent protections on what would be an otherwise lower-margin generic medicine. That allows for more pricing power because of improved outcomes and renewed exclusivity. (Still, there’s certainly not as much pricing power as for an all-new drug, points out Goonewardene.)

    This is just one delivery mechanism and one condition. There’s still huge a opportunity. Taking OptiNose as one example, the device is also being adapted to transform treatments for sinus polyps and chronic sinusitis using the widely-known drug fluticasone (you may know this by its brand name: Flonase). That would open up an under-served market worth at least $1.5 billion, OptiNose said.

    Even bigger: the nasal cavity is the only area where the brain meets the outside world. The potential to better treat central nervous system diseases such as Autism and Alzheimer’s by reaching the brain directly could transform treatments for those diseases, the company said.

    To be sure, there’s still a long way to go to confirm such things in clinical testing, and new delivery methods still rely on the library of drugs available, as well as the limitations of the human body. Progress is starting to reach the market, and it has the potential to make already good drugs even more effective.