As 2018 comes to a close, analysts, journalists, investors and industry-watchers are studying their crystal balls to see what trends to watch in the upcoming year. Here are 7 trends most likely to be hitting the news cycle.
#1. Alzheimer’s. 2018 was a bad year for Alzheimer’s drug development … but so was 2017, 2016, 2015 and every year before that. There were at least half-a-dozen big Alzheimer’s drug failures this year, and it seems likely that there will be more in 2019. But every failure leads to a better understanding of the disease. All eyes will be on Biogen as its clinical trials continue on aducanumab in early-stage Alzheimer’s. And vTv Therapeutics has everyone wondering if its lead compound, azeliragon, can rise to expectations in two Phase III trials in Alzheimer’s that are both expecting readouts in 2019, one in the first quarter, the other by the end of the year. And those are only a couple expected to be under the microscope next year.
#2. Paying for innovation. STAT listed “How are we going to pay for this stuff?” as one of their top biotech trends for 2019. For example, they noted how dramatically effective CAR-T immuno-oncology therapies are for cancer, in addition to gene therapies such as those expected in 2019 for spinal muscular atrophy (SMA). But there is speculation that if Novartis’ SMA gene therapy is approved, it could run as high as $5 million a dose.
“What Novartis chooses to charge—and how governments and insurers react—will be of staggering importance to biotech,” STAT writes. “If the SMA gene therapy, which appears to be truly revolutionary, proves to be a commercial failure, it’ll be an ominous sign for the scores of companies—and billions of dollars—invested in similar projects.”
#3. Politics and drug prices. Possible presidential candidates for the 2020 election are already putting out feelers, forming committees and raising money. And healthcare and drug prices are expected to be at the top of hot-button issues. Just last week, in a December 17, Washington Post op-ed, Senator Elizabeth Warren (D-MA), proposed The Affordable Drug Manufacturing Act, which would allow the Department of Health and Human Services (HHS) to manufacture or contract out the manufacture of generic drugs. This seemingly radical idea certainly sounds like a prelude to a presidential run, and you can expect candidates for both parties to take aim at drug pricing and rising healthcare costs.
#4. Selling drugs. Although criticism of the pharmaceutical industry is common, both publicly and in political circles, the reality is developing and successfully selling drugs is incredibly expensive and difficult. As the first trend points out, there are a lot of failures—Alzheimer’s is just one prominent example—which represents hundreds of millions of dollars spent on failed projects.
But “success” comes with many challenges, not just in getting to market, but being profitable once a drug gets to the market. STAT notes, “Time and again, we’ve seen biotech companies race through clinical development and on to an FDA approval, pulling their stock prices upward along the way only to tank in the early months of commercialization as the realities of marketing erase investors’ optimism.”
Paul Matteis, an analyst with Steifel, told STAT in November, that managing expectations “is probably one of the biggest challenges that faces biotech companies transitioning from Phase III to commercial stage. If you’re a company, you have to walk the balance right.”
#5. Opioids. The opioids crisis isn’t over. This year marked a number of lawsuits filed against opioid-makers by both state and local governments. The crisis has resulted in more than 70,000 annual deaths in recent years, but efforts by the government and law enforcement do not seem to be making a big change. And in November, the FDA approved a new and powerful opioid painkiller called Dsuvia, made by AcelRx Pharmaceuticals, that is reported to be 1,000 times more powerful than morphine. This resulted in public criticism, which Food and Drug Administration (FDA) Commissioner Scott Gottlieb defended, arguing the agency needs to consider approving any new opioid pain medication that fills a medical need, regardless of the epidemic.
#6. IPOs. It was a record year for biotech initial public offerings (IPOs). Some were individual record-breakers—Moderna Therapeutics, Allogene Therapeutics and Rubius Therapeutics. The total for the year is around $8.2 billion raised, breaking 2014’s record of $6.5 billion.
STAT writes, “But it’s worth revisiting the 2015 aspect…. IPOs were bountiful back then, too, but a swoon in stock prices led to negative returns at the median, and investors’ willingness to buy into biotech cratered. There were half as many biotech IPOs in 2016 as the year prior, and investors pulled roughly $6.5 billion out of the sector in the ensuing 12 months.”
That said, Gossamer Bio just filed for an IPO to raise $264.5 million to fund its immunology clinical programs. And due to changes in the Hong Kong Stock Exchange rules that allow biotech companies without a product to file IPOs, numerous international biotechs are looking to that exchange as a potential option to raise funds.
#7. CRISPR. Earlier this month, He Jiankui, a researcher from the Southern University of Science and Technology of China announced that a set of twins had been born in which he had used CRISPR gene editing to modify the embryos. He made this announcement at the Second International Summit on Human Genome Editing held at the University of Hong Kong. He Jiankui modified the CCR5 gene, which should make the babies less susceptible to HIV infection. This was met with resounding condemnation and the launch of various investigations by the Chinese government, Southern University, Rice University and the U.S. National Institutes of Health (NIH). It’s unlikely that this story is over.
And on the broader topic of CRISPR, there are several legitimate and well-regulated clinical trials ongoing in Europe, the U.S. and China, that use CRISPR to treat specific diseases in adult patients. In addition, the CRISPR techniques and approaches are being developed. For example, researchers at UC San Francisco recently published research in the journal Science describing their use of a modified version of CRISPR gene editing to stimulate the activity of certain genes, resulting in the prevention of severe obesity in mice who had a genetic predisposition to extreme weight gain.
Of particular importance was that this long-lasting weight control occurred without edits to the genome.
The story of He Jiankui and the sets of twins is likely to continue into 2019, but expect other CRISPR stories to float to the top as well.
“诺华公司选择收费的方式以及政府和保险公司的反应将对生物技术具有惊人的重要性，” STAT 写道。“如果SMA基因疗法被证明是一种商业上的失败，那么对于那些在类似项目上投资数十亿美元的公司来说，这将是一个不祥之兆。”
但“成功”带来了许多挑战，不仅仅是进入市场，而且一旦药物进入市场就会盈利。 STAT 指出，“我们一次又一次地看到生物技术公司在临床开发和FDA批准方面的竞争，在商业化的前几个月将其股价一路上涨，因为市场营销的现实消除了投资者”乐观。”
Steifel的分析师保罗· 马蒂斯（Paul Matteis）在11月份告诉STAT ，管理期望“可能是生物技术公司从第三阶段过渡到商业阶段所面临的最大挑战之一。如果你是一家公司，你必须走平衡。“
＃5。阿片类药物。阿片类药物危机尚未结束。今年是州和地方政府针对阿片类药物制造商提起的一系列诉讼。这场危机导致近年来每年死亡人数超过7万人，但政府和执法部门的努力似乎没有发生重大变化。11月，FDA批准了一种名为Dsuvia的新型强效阿片类止痛药，由 AcelRx Pharmaceuticals生产，据报道它比吗啡强1000倍。这引起了公众的批评，美国食品和药物管理局（FDA）专员 Scott Gottlieb 辩护说，该机构需要考虑批准任何满足医疗需求的新型阿片类止痛药，无论疫情如何。
STAT 写道，“但值得重新审视2015年的方面...... 当时的IPO也很丰富，但股价的低迷导致中位数的负回报，投资者购买生物技术的意愿下降。2016年的生物技术IPO数量是前一年的一半，投资者在随后的12个月内从该行业中撤出约65亿美元。“
也就是说， Gossamer Bio 刚刚申请 IPO筹集2.645亿美元资助其免疫学临床项目。而且由于改变在香港联交所的规则，允许生物技术公司没有产品上市文件，众多国际生物技术公司正在寻找这种交流为筹集资金潜在的选项。
在更广泛的CRISPR主题上，欧洲，美国和中国正在进行一些合法且监管良好的临床试验，这些临床试验使用CRISPR治疗成人患者的特定疾病。此外，正在开发CRISPR技术和方法。例如，加州大学旧金山分校的研究人员最近 在“ 科学 ” 杂志上发表研究，描述他们使用修饰版的CRISPR基因编辑来刺激某些基因的活动，从而预防具有极端遗传倾向的小鼠的严重肥胖体重增加。