????新藥品的研發(fā)成本正在繼續(xù)飆升。根據(jù)來自塔夫茨藥物開發(fā)研究中心的數(shù)據(jù)，開發(fā)、測(cè)試一款新藥并通過監(jiān)管機(jī)構(gòu)的批準(zhǔn)，可能要耗費(fèi)制藥公司25億美元以上，比10年前翻了一倍還多——2003年，制藥公司將新藥推向市場(chǎng)上的費(fèi)用約為8.02億美元（按2013年購(gòu)買力計(jì)算約為10.4億美元）。

????一些制藥公司和生物科技公司都想知道怎樣才能加大投入產(chǎn)出比，而其中的一種方法就是讓現(xiàn)有的藥品，也就是那些已經(jīng)經(jīng)過測(cè)試和認(rèn)證的知名藥品，變得更加有效。

????彭博社智庫(kù)生物科技分析師阿斯卡?古納瓦迪尼認(rèn)為：“隨著市面上的仿制藥越來越多，這種發(fā)展趨勢(shì)是很自然的。各大公司都在研究新的給藥方法，或是將現(xiàn)有藥品以新的方法進(jìn)行組合。這是一種可行的辦法?！?/p>

????一些知名藥企已經(jīng)進(jìn)入這個(gè)領(lǐng)域，其中包括阿特維斯和梯瓦制藥等公司。其他規(guī)模較小的藥企也在尋求能夠顛覆游戲規(guī)則的創(chuàng)新，比如MannKind公司研發(fā)的吸入式胰島素Afrezza，以及Heron Therapeutic公司極具科技含量的高分子聚合物給藥平臺(tái)Biochronomer，它可以讓現(xiàn)有注射類藥物的藥效更加持久。

????古納瓦迪尼表示：“如果采用一種已經(jīng)通過認(rèn)證的藥物，就相當(dāng)于削減了認(rèn)證過程。這種方式的風(fēng)險(xiǎn)更低，因?yàn)槊绹?guó)食品藥品監(jiān)管局（FDA）很喜歡這種做法?！?/p>

????在費(fèi)城郊外，一家名叫OptiNose的生物科技公司就在深耕這一領(lǐng)域。該公司發(fā)明了一款相對(duì)來說并不是特別高科技的設(shè)備。這款設(shè)備可以將藥物送到它需要去的地方，進(jìn)而有望改變傳統(tǒng)的治療方式。

????這款塑料設(shè)備利用人類的自然呼吸來關(guān)閉鼻腔，然后將藥物送至鼻腔深處。當(dāng)你通過嘴巴大力呼氣時(shí)，軟腭會(huì)關(guān)閉通向鼻腔的氣道，這也就是為什么你無法同時(shí)用嘴巴和鼻子大力吹氣的原因。它的作用其實(shí)就相當(dāng)于封閉鼻腔，使藥物可以在那個(gè)封閉空間進(jìn)行循環(huán)，同時(shí)你的呼吸會(huì)將藥物直接送至鼻竇。

????OptiNose正在與Avanir公司進(jìn)行合作，而這款產(chǎn)品的首個(gè)用途（治療偏頭痛）有望很快獲得FDA的批準(zhǔn)。臨床研究顯示，與口服藥物相比，這種靠呼吸給藥的設(shè)備使藥物進(jìn)入血液的速度更快，同時(shí)需要的藥物劑量也更小。它的藥效幾乎像注射一樣快，但病人無需挨上一針。

????開發(fā)這種新型給藥機(jī)制的成本大約只有3000萬到5000萬美元。這還包括正在接受FDA審核的另一項(xiàng)針對(duì)慢性鼻竇炎的研發(fā)費(fèi)用。

????Optinose公司CEO彼得?米勒指出：“藥品開發(fā)最難的部分是，很多好藥由于安全問題而無法面市。在藥品開發(fā)的早期階段，大家都知道出現(xiàn)了非常好的藥效，他們才會(huì)開始進(jìn)行動(dòng)物實(shí)驗(yàn)并尋找副作用。但由于我們采用的藥品已經(jīng)在人身上用過了，特別是我們的頭兩款藥品已經(jīng)被人使用過數(shù)百萬次了，因此我們的開發(fā)風(fēng)險(xiǎn)和監(jiān)管風(fēng)險(xiǎn)與合成一種新藥相比，完全不在一個(gè)級(jí)數(shù)上。”

????由于使用的劑量更少、給藥更快、或提高了藥效，這些更好的給藥手段不僅降低了研發(fā)成本、優(yōu)化了藥品利用率，還幫助制藥公司延長(zhǎng)了一些專利原本要過期的藥品的專利保護(hù)權(quán)。藥效的改善和專利權(quán)的更新，賦予了制藥公司更大的定價(jià)權(quán)（不過古納瓦迪尼指出，這種定價(jià)權(quán)顯然還是比不上開發(fā)一款全新的藥物）。

????盡管這種給藥機(jī)制解決的只是一種病癥，但它依然面臨非常巨大的商機(jī)。以O(shè)ptiNose為例，該設(shè)備目前也被用來臨療鼻息肉和鼻竇炎，采用的藥物是廣為人知的氟替卡松。OptiNose公司表示，它有可能打開一個(gè)市值至少在15億美元的市場(chǎng)。

????它還有著更大的前景：鼻腔是大腦與外部世界唯一接觸的直接接觸區(qū)域。該公司表示，未來OptiNose有可能通過鼻腔給藥，在治療自閉癥和阿爾茨海默癥等中樞神經(jīng)系統(tǒng)疾病上達(dá)到更好的效果。

????當(dāng)然，要在臨床測(cè)試中確認(rèn)這些事，還有很長(zhǎng)的一段路要走。此外，新的給藥方法仍然無法超越現(xiàn)有藥物和人體的極限。盡管如此，這種技術(shù)進(jìn)步正在進(jìn)入市場(chǎng)，而且有望顯著提升現(xiàn)有好藥的治療效果。（財(cái)富中文網(wǎng)）

????譯者：樸成奎

????審校：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.