Pharmabros, Designer Babies, And Other Final Words For 2015

Xconomy National — 

Every three months, Oxford Dictionaries releases its new entries, and modern language mavens everywhere have a field day.

A few of my favorites from the summer update: weak sauce, microaggression, cupcakery, and at the risk of perpetuating wholly unfair stereotypes about journalists, beer o’clock.

With that, I kick off my final column of 2015, a year-end smorgasbord—originally Swedish, entered the English language in the late 19th or early 20th century—of looks back and peeks ahead.

I’ll start with my nominee for the next update: pharmabro.

The term, of course, refers to Martin Shkreli, the perpetually attention-seeking now-former CEO of several companies who spent 2015 pissing off practically everyone, and vice versa, and ended the year out on a $5 million bond after his arrest on fraud charges.

He even got into it with the Wu-Tang Clan, whose one-of-a-kind album Once Upon A Time in Shaolin Shkreli bought at auction for $2 million. (When the rap supergroup learned he was the buyer, they donated “a significant portion” of the loot to charity, according to Bloomberg. Shkreli said they were just covering their, well, booties, as those hip-hop folks like to say.)

Shkreli the pharmabro—others around the Internet assigned him far less charitable neologisms—managed to give anger about drug prices a white-hot focal point: his own 32-year-old face, which, by live streaming himself on the Internet and keeping up constant Twitter patter, he helped project everywhere.

Going into 2015, I pinpointed drug pricing as one of five potential flashpoints for biopharma. This was far from rocket science; everyone following the business knew more public outrage was coming. Exactly one year ago, powerful drug purchasing agent Express Scripts (NYSE: ESRX) said that the newly launched Viekira Pak combination from AbbVie (NYSE: ABBV) and Enanta Pharmaceuticals (NASDAQ: ENTA) would be the only hepatitis C treatment it would buy for its customers. It was a slap-down of Gilead Sciences (NASDAQ: GILD), which once upon a time was the Shkreli of biopharma, thanks to the price tags for hepatitis C treatments sofusbuvir (Sovaldi) and its follow-on Harvoni: $84,000 and $94,500 per course, respectively.

Gilead CEO John Martin and his colleagues have never galvanized the haters quite like Shkreli, but one could argue they did no better than Shkreli winning over hearts and minds with two standard pro-pharma arguments: Drugs are expensive to make, so high prices help support more innovative R&D. (Shkreli tried to use that one about Daraprim, the anti-parasitic drug that helps saves the lives of people with HIV, after he jacked up the price from $13.50 to $750 a tablet.)

Also, the costs of caring for patients with chronic diseases are massive, therefore an exorbitant price for a relatively short course of a curative drug like sofosbuvir in fact saves money in the long run. (In the short run, however, what does it do to strained state budgets?)

As we pivot into 2016, will some of the outrage over drug prices be siphoned off, as Shkreli enters the pop-culture swamp where quasi-celebrity meets personal and legal train wreck? Will news coverage of his fraud trial—if and when he gets there—and the political circus of the presidential race detract from the real issue of unsustainable healthcare costs in the U.S., or will it amplify them?

I’ll do my small part here to stump for the real issues. First, keep in mind through the months to follow that drug prices account for less than 10 percent of total U.S. healthcare spending, according to 2013 data from the U.S. government. They’re a part of the healthcare cost problem, but only one small part.

Still, one way to bring down our drug costs is to let Medicare—the largest drug buyer in the world—negotiate prices. By law, it cannot do so. As I noted earlier this year when Shkreli first made himself a target with his Daraprim price-gouging, let’s not forget that our own lawmakers have allowed drug makers to gouge Medicare for a lot of old warhorse drugs, led by heartburn treatment omeprazole (Nexium). The top ten drugs Medicare bought in 2013 added up to $18 billion, or 17 percent of the program’s total spending that year.

Now we head into an election year. Democratic front-runner Hillary Clinton has vowed to fight price gouging and give Medicare negotiation rights. Some Republican candidates have at least paid lip service to alarmingly high drug costs.

Egregious tax dodges epitomized by Pfizer’s “inversion” acquisition of Irish-domiciled Allergan don’t seem to anger the public quite the same way, even though the executives involved are pulling a Shkreli: Exploiting what’s legal to do what’s unethical, then trotting out bromides of doing what’s best for shareholders and boosting innovation.

So it looks like industry critics need Pharmabro Numero Uno to do his thing, keep up the mugging and tweeting and primping (despite comments to the Wall Street Journal this week that he wants to lower his profile). For people who want big changes in the way the drug business does business, having Shkreli to rail against all year could be, well, just what the doctor ordered.

All right, so I predicted in January that drug pricing would remain a hot topic all year. Big whoop. What about my other big questions for 2015? Let’s have a look.

—“What happens when cell-based cancer immunotherapy has its first big setback?” I asked that question as the immunotherapy frenzy was helping the entire biotech sector make its best bull run ever. Since then, the markets have deflated. Juno Therapeutics (NASDAQ: JUNO), Kite Pharma (NASDAQ: KITE), and Novartis, whose clinical programs for a form of cell therapy known as CAR-T had already shown early promise, made more progress in 2015. Novartis was the first to report Phase 2 data from a CAR-T program, for example. There were no big setbacks, but there was acknowledgment that patients with blood-borne cancers will likely do better with an extra dose of chemotherapy before receiving CAR-T therapy. Other obstacles for CAR-T, such as large scale manufacturing or making the leap to treat solid tumors such as breast, lung, and ovarian cancers, have yet to be solved, as my colleague Ben Fidler reported in September.

Investors hate negative surprises, and there weren’t any whoppers in the CAR-T field this year. One positive surprise came from Cellectis (NASDAQ: CLLS), a French drug developer that established a U.S. beachhead in New York this year. Using its version of gene editing called TALEN, the company has created “off the shelf” T cells to treat blood cancer. The DNA of a donor’s T cells are snipped with molecular scissors to make them friendly to a recipient’s immune system. When the cells are infused into the recipient, they attack the cancer, not the patient’s healthy cells. That is the goal, at least: Cellectis’s first product, UCART19, has not been approved yet for clinical trials.

Then news emerged in November that an infant in desperate straits with leukemia was treated with UCART19. It was a special request from her parents, not part of a trial. UCART19 helped bring the baby girl, Layla Richards, back from the brink and allowed doctors to try again a bone marrow transplant, which hadn’t worked previously. As of November, Layla had recovered. In other words, it worked, but it wasn’t part of a trial, and other factors were involved. The halo around Cellectis’s stock wore off quickly. Just like the shares of Juno, Kite, and Bellicum Pharmaceuticals (NASDAQ: BLCM), all making personalized, self-donated “autologous” CAR-T products, Cellectis’s shares tumbled in early December around the year’s big hematology conference.

To see if Layla’s recovery is a fluke or part of a promising therapeutic future for others, Cellectis will have to watch from the sidelines. Next year, two larger companies, Servier and Pfizer (NYSE: PFE), will take UCART19 into clinical trials, because Cellectis sold Servier the global rights in 2014, which in turn sold U.S. rights to Pfizer last month. The first trial could start in the U.K. soon.

Other CAR-T programs to watch include those from Novartis, Kite, and Juno, in pivotal trials for children and adults with acute lymphoblastic leukemia, or ALL, meaning the data could be enough to spur an FDA approval in 2016 or 2017. “ALL is really the low-hanging fruit of CAR-T,” says independent investor Brad Loncar, who has created a stock index of companies developing CAR-T and other forms of cancer immunotherapy.

After ALL come weightier challenges. Kite is also aiming for pivotal data next year in non-Hodgkins lymphoma. Another program to watch is CAR-T against multiple myeloma, the second most prevalent blood cancer. Bluebird Bio (NASDAQ: BLUE) could have a cell therapy in the clinic in 2016, while the NIH continues a Phase 1 trial with an earlier version of Bluebird’s therapy.

Also proving more challenging to treat with CAR-T are solid tumors, such as breast, ovarian, and pancreatic, but 2016 should bring the first significant data sets from early trials in a few indications.

—“Is it time to stop worrying and love the IPO window?” After I asked that question, eight more months passed before the public markets slowed. From January 1 to August 31, about 40 life sciences companies went public in the U.S. Since September 1, 19 have debuted, according to I ask you: Is that the popping of a bubble, or the slow descent of a feather on a windless day? Contemplating that metaphor is like being at a Zen retreat, except you’re reading a column on the Internet.

Biomedical scientists and investors are always wary of changes in regulation and policy. Those risks have been reduced in what one might call “the Hamburg Era.” Peggy Hamburg took the reins of the FDA in 2009 and presided over a drug approval boom. In her final full year, 2014, the agency approved 41 new and novel drugs, the highest total since 1996 and a big leap over the years before Hamburg took the post. Hamburg has handed the baton to Rob Califf, a Duke University cardiologist whose ties to industry have been a point of contention. So far in 2015, the FDA has approved 45.

Although drug pricing has become a talking point, the U.S. political apparatus is squarely (and, if you’re a critic, disturbingly) aligned with getting more drugs to market faster. That won’t change with the blockbuster legislative package known as “21st Century Cures.” It includes FDA reform and more NIH funding, and it passed through the House of Representatives this summer but has since stalled in a Senate committee. According to committee chair Lamar Alexander (R-TN), speaking on C-SPAN, one hang-up is whether the NIH funding should be guaranteed for several years or determined year to year. At the start of 2015, the bill’s backers hoped to have President Obama sign it into law before 2016. That now looks unlikely.

But winds continue to favor biomedical research; the new budget passed earlier this month actually boosted NIH funding by 6.6 percent, the biggest bump in 12 years. I still contend it would take another external shock to grind the biopharma financing gears to a halt.

—“A bigger question, perhaps, is whether the healthcare field starts to pivot from pharmaceutical approaches to more holistic approaches.” Just before 2014 turned into 2015, Danish drug maker Novo Nordisk got FDA approval for a weight-loss injection—a higher-dose version of Novo’s diabetes drug liraglutide, rebranded as Saxenda. It was yet another old drug recast to grab a piece of the anti-obesity market. Previous drugs of recent vintage had not gained much traction. One year later, the pressure to solve problems like epidemic obesity with something other than drugs is even greater. The four drugs on the market still haven’t made much impact. And a possible new entrant in the field, beloranib, has been suspended by the FDA after two patients died in a Phase 3 trial to treat the rare genetic disease Prader-Willi Syndrome, which causes uncontrollable hunger. Even if beloranib is eventually successful in Prader-Willi, the deaths have damaged Zafgen’s chances of expanding it to a more general population.

American obesity rates have recently moved slightly in the right direction among preschoolers, but overall obesity is still a crisis, affecting more than a third of all adults and 17 percent of children. In May, I asked whether we should count on drugs—as we have with HIV and cancer—to make a dent in our massive societal weight problem.

Many say that drugs will remain necessary, which is hard to argue with when it comes to extreme cases like Prader-Willi. But a confluence of factors could continue to push back against the pharmaceutical solution. Backlash against drug prices is one; better diet practices, like getting sodas out of schools, is another; and ever-growing digital health solutions, either without drugs or combined with drugs, is a third.

It wasn’t among my new year’s predictions—shame on me—but gene editing captured the world’s imagination nearly as much as Shkreli. Work continued apace in academic labs to make new and better tools, as well as in small and large companies alike to make new therapies. Nothing is close to becoming an approved medicine; the most advanced is an HIV treatment—immune cells edited with a system called zinc fingers from Richmond, CA-based Sangamo Biosciences (NASDAQ: SGMO)—in Phase 2 trials. The T cells that helped cure Layla Richards were edited with a system called TALEN and will start clinical trials soon.

But the speed at which the the gene editing system called CRISPR-Cas9 has developed and spread means CRISPR-edited therapies could be tested in humans sooner than we think. Editas Medicine CEO Katrine Bosley said her company aims to start a clinical trial for a rare form of blindness in 2017. Will that be the first time humans have their genes edited with CRISPR? Don’t be surprised if someone moves even faster. There are many hurdles to jump to make that happen, but CRISPR developments, such as new “scissors” other than the Cas9 enzyme, or a wider range of guides for those scissors, or more accurate editing, seem to issue forth every day.

The biggest development in the CRISPR world in 2015, however, was the work of Chinese scientists, published in April, that they edited non-viable human embryos—those that would not have led to a live birth—with CRISPR scissors. The scientists reported that the experiment, to change the genetic defect that causes the blood disorder beta-thalassemia, did not go well.

But it underlined the possibility of genetically altered humans passing down their traits, a scenario that some say could lead to parents designing their babies for looks and skills, and others say could wipe out terrible inherited diseases. (These possibilities aren’t mutually exclusive.)

Scientists, bioethicists, and others gathered in Washington, D.C., to debate those scenarios and discuss guidelines. The summit’s organizers, chaired by Nobel Prize winning biologist David Baltimore, issued a strong statement against the modification of human eggs, sperm, and embryos—the germline—in ways that allow genetic traits to be passed from one generation to another, but they declined to call for a ban or moratorium. They also approved of human germline editing in basic research settings, as long as viable fetuses aren’t being produced.

It seems inevitable, though, that someone will flout the recommendation, perhaps in a country where the rules are lax, perhaps not. Will it be 2016? My prediction is yes—or at least a scientist will claim to have done so, even if it lands him or her in hot water. After all, what we’ve seen in 2015 with Shkreli (and in 2005 with Woo Suk Hwang, and many times before and after) is that the ego can help an ambitious person crash through all kinds of boundaries, not the least of which is good judgment.

Happy holidays. See you in 2016.