Despite a roiling political environment on both sides of the Atlantic and what Science called "epic estrangement" between the U.S. president and the scientific community, the biopharma industry produced dazzling clinical breakthroughs in 2017 while U.S. regulators logged record nods, including the first for gene therapy. But not all was well in the industry. States joined federal lawmakers in seeking to curtail soaring drug prices – the likes of which drew rebukes even from the FDA's top dog – and lawsuits began to target the catastrophe of opioid abuse. Add to the mix a sea change in U.S. tax law at the tail end of the year – too late for its impact to be felt in 2017 – and the biopharma world could look very different this time next year.


At long last, the FDA gave the green light to gene therapy, signaling at the same time that the space might move into the fast lane.

The historic move came in August when the agency approved the chimeric antigen receptor T-cell (CAR T) immunotherapy Kymriah (tisagenlecleucel, Novartis AG) to treat children and young adults with B-cell acute lymphoblastic leukemia. FDA Commissioner Scott Gottlieb called the approval "an important milestone in a long journey we've been on to transform clinical medicine by using modern advances in genomics." The price tag: $475,000 for a one-time treatment, although officials at Basel, Switzerland-based Novartis committed to work with payers on outcomes-based pricing, in which treatment is reimbursed only when patients respond to therapy. (See BioWorld, Aug. 31, 2017.)

Weeks later, the FDA gave a similar nod to Kite Pharma Inc.-developed CAR T Yescarta (axicabtagene ciloleucel, Gilead Sciences Inc.) to treat certain types of non-Hodgkin lymphoma (NHL). Gilead, of Foster City, Calif., listed the one-time therapy in the U.S. at $373,000 but without outcomes-based pricing. (See BioWorld, Oct. 20, 2017.)

Both CAR T therapies were approved under the FDA guidance for human somatic cell therapy and gene therapy on the basis of modifying the genetic material of living cells. And the agency's receptivity to gene therapy didn't stop there. In December, its nod for Luxturna (voretigene neparvovec-rzyl, Spark Therapeutics Inc.) marked the first U.S. gene therapy to target an inherited disease, caused by mutations in a specific gene. The treatment was approved to treat children and adults with confirmed biallelic RPE65 mutation-associated retinal dystrophy, an ultra-rare progressive disease that leads to vision loss and may cause blindness. (See BioWorld, Dec. 20, 2017.)

Spark's more "traditional" gene therapy delivers a normal copy of the RPE65 gene directly to retinal cells, using a naturally occurring adeno-associated virus, modified using recombinant DNA, as the delivery vehicle. The Philadelphia-based company plans to disclose pricing in early January but maintained that its one-time treatment "is worth in excess of $1 million."

Gottlieb described Luxturna's approval as "another first in the field of gene therapy – both in how the therapy works and in expanding the use of gene therapy beyond the treatment of cancer to the treatment of vision loss" and predicted gene therapy "will become a mainstay in treating, and maybe curing, many of our most devastating and intractable illnesses." In 2018, the FDA plans to offer a suite of disease-specific guidance documents on the development of gene therapy products that will be part of what Gottlieb called "a modern, comprehensive framework for how we'll help advance the field of gene therapy while making sure new products meet the FDA's standards for safety and benefit."

With the gene therapy window wide open in the U.S., the land grab for assets began in earnest with Gilead's $11.9 billion acquisition of Kite, weeks before Yescarta's approval, as partnering deals for CAR T and other gene therapies ramped up. (See BioWorld, Aug. 29, 2017.)

Expect more of the same in 2018. Cortellis Competitive Intelligence cites more than 1,000 gene therapy candidates in development, including 600 CAR T assets. Many are moving to the clinic directly from academic institutions, and not all are advancing in the U.S. Although the U.S. holds the edge in CAR T development, with 117 registered trials, China is running 93 trials, according to Cortellis. The U.S. also is leading overall gene therapy development, with more than 3,800 registered trials, followed by Japan with more than 1,100 and China with nearly 900.


In a year of U.S. governance laden with superlatives, 2017 can honestly be called the biggest year yet for the FDA. Through Dec. 21, the agency had approved 46 new molecular entities (NMEs), ticking past the highest number on record – 45 in 2015 – and improving significantly on the 2016 count of 21 NMEs approved. The agency may not be done yet. In past years, the regulator has added new approvals straight through the last weekday of the year. (See related story in this issue.)

The big batch of innovative medicines included first-ever nods in some indications while others raised eyebrows. Among the year's highlights were the three groundbreaking gene therapies, Kymriah, Yescarta and Luxturna; the first treatment designated as an extended adjuvant therapy in patients with early stage, HER2-positive disease, Nerlynx (neratinib, Puma Biotechnology Inc.); the first FDA-approved multiple sclerosis (MS) drug that provided benefit to patients with primary progressive MS, Ocrevus (ocrelizumab, Genentech/Roche Holding AG); and the first therapy for children with the rare and fatal neurodegenerative condition ceroid lipofuscinosis type 2, Brineura (cerliponase alfa, Biomarin Pharmaceutical Inc.). The year also yielded the highest number of generic medicine approvals in FDA history, according to Commissioner Scott Gottlieb. (See BioWorld Today, March 30, 2017, April 28, 2017, and July 19, 2017.)

Across the Atlantic, recommended approvals carried on closer to their typical pace. The EMA's Committee for Human Medicinal Products closed out 2017 having recommended approval of 30 new non-orphan drugs and 19 orphan drugs. That tally was marginally ahead of the previous year, when the CHMP backed 28 new non-orphan drug approvals and 18 new orphan drug approvals.


Although the opioid epidemic comes in at No. 3 on the BioWorld list of top biopharma news stories, it arguably was the top public health concern in the U.S. in 2017 as policymakers struggled to curb its rising toll.

Opioid addiction was recognized as the leading cause of unintentional death in the U.S., outpacing the number of deaths due to shootings and vehicle accidents combined. That statistic resulted in an all-hands-on-deck response, with the federal government seeking to change how opioids are prescribed, beef up prevention programs, and encourage better emergency and long-term treatments.

President Donald Trump created the President's Commission on Combating Drug Addiction and the Opioid Crisis and charged it with recommending commonsense solutions. He later declared opioid addiction a national public health emergency. (See BioWorld, Oct. 27, 2017.)

When Scott Gottlieb took the helm of the FDA this year, he made the opioid epidemic the most immediate priority on his to-do list. One of his first steps was to direct the agency to rethink the safety of abuse-deterrent formulations. Consequently, the FDA asked Endo Pharmaceuticals Inc., of Malvern, Pa., to remove its abuse-deterrent Opana ER (oxymorphone hydrochloride) from the market due to the public health consequences of abuse. (See BioWorld Today, April 6, 2017.)

Gottlieb also put the development and approval of generic versions of addiction and overdose treatments on the front burner to make them more affordable through competition. Meanwhile, the NIH funded research into safer ways of treating chronic pain and developing nonaddictive alternatives to opioids.

Since January, the U.S. government has allocated more than $1 billion to fund prevention programs, treatment, monitoring programs, and other care in communities, inpatient settings and correctional systems. Lawmakers continue to request money to help their states fight the problem.

The epidemic spilled over into Canada, where Health Canada is working with manufacturers to update the labeling of 508 prescription opioid products to include more risk information. Canada's Minister of Health Ginette Petitpas Taylor called on regulators to identify additional measures to address what she said is a crisis "unlike any other public health crisis we have experienced in recent years."

As the epidemic spreads, opioid manufacturers are facing lawsuits from shareholders and federal, state and tribal governments. Some legal experts predict such action could result in a mass settlement akin to the 1998 Tobacco Master Settlement Agreement, which cost the big tobacco companies more than $200 billion.


U.S. prescription drug prices ranked among the top biopharma news stories for the third year in a row. The outrage about list drug prices escalated from last year's campaign rhetoric to become Americans' top priority for congressional action in 2017.

In a news conference just days before taking office in January, Trump said drug companies were "getting away with murder." The president softened his tone a few weeks later in a preface to a private meeting with the Pharmaceutical Research and Manufacturers of America (PhRMA) and the heads of several major U.S. drug companies, but he reiterated that drug prices must come "way down." (See BioWorld Insight, Jan. 23, 2017, and BioWorld Today, Feb. 1, 2017.)

With the need to reduce drug prices as one of the only areas of bipartisan agreement in Washington, drug companies refrained from the hefty price increases of the past, but they didn't roll back prices and new drugs continued to launch at budget-busting prices. (See BioWorld Today, March 2, 2017.)

The $89,000 list price Marathon Pharmaceuticals LLC set for its newly approved Duchenne muscular dystrophy drug Emflaza (deflazacort), which was available outside the U.S. as a generic, whipped up such a firestorm that the drug company immediately paused its commercialization plans. A month later, Marathon, of Northbrook, Ill., sold the drug to PTC Therapeutics Inc., of South Plainfield, N.J., for $140 million. (See BioWorld Today, Feb. 13, 2017, Feb. 15, 2017, and March 17, 2017.)

Other drug company "shenanigans," as the FDA's Gottlieb called them, included efforts to game the patent and regulatory systems to protect or extend brand monopolies. The most egregious move of the year, in congressional opinion, was Allergan plc's transfer of six patents protecting dry-eye drug Restasis (cyclosporine) to the Saint Regis Mohawk Tribe to shield the patents from inter partes review challenges. (See BioWorld, Sept. 20, 2017.)

Meanwhile, Congress held numerous hearings to investigate drug prices and explore solutions such as allowing direct government negotiations, importing cheaper drugs from Canada and value-based pricing. While drug companies continue to push for value-based pricing, changes to Canada's Patented Medicines Regulations intended to make prescription drugs more affordable in that country could increase congressional interest in importation. (See BioWorld, Dec. 7, 2017.)

As Congress continued to discuss drug prices, states took action, passing laws requiring transparency and justification of certain price increases. Touting its new law as the way forward for the nation, California passed one of the most comprehensive state transparency laws, which is now being challenged by PhRMA as unconstitutional. (See BioWorld, Oct. 10, 2017.)


It's now 457 days until Brexit and – despite the first phase of negotiations concluding – the industry faces a fog of uncertainty and impossible demands in 2018.

Most keenly, the EMA's edict that companies proceed on the basis that the U.K. becomes a third party on March 30, 2019 – completely outside the fold of European medicines regulation – is a deadline impossible to meet. (See BioWorld Today, May 2, 2017.)

In large part, that is because the EMA itself will not have the capacity to handle the bureaucratic overhead, given the volume of paperwork which will be generated, and the fact that the agency will be embroiled in relocating from London to Amsterdam. (See BioWorld, Oct. 2, 2017.)

The requirement for companies to replicate physical infrastructure, in the shape of validated labs to carry out batch release and quality control of drugs, also will be difficult to meet, given the timeline.

Then there is the issue of the loss of the U.K. Medicines and Healthcare products Regulatory Agency's (MHRA) expertise. The EMA insouciantly stated it has "developed a methodology for the redistribution of the work," currently done by MHRA. But again, there is simply not enough time to train enough people and to fill the mega hole left in terms of MHRA's contribution to scientific committees and its leadership in pharmacovigilance, not to mention the huge contribution of the U.K.'s National Institute for Biological Standards and Control to the development of assays and regulatory science.

On top of all of that, the EMA has set itself what Steve Bates, chief executive of the U.K. BIA, described as an "undeliverable timetable" for its removal to Amsterdam, not least because its new office building will still be under construction.

One bit of clarity on the divorce terms emerging at the conclusion of phase one of the negotiations was that both sides agree there should be a transition period after the Brexit date of March 29, 2019, during which the rules will stay the same. The length of the transition is expected to be decided by March 2018. Once agreed, the EMA may stretch the timetable it has set for companies, though the question of whether the U.K. becomes a third party will be subject to subsequent negotiations.

Adding to the continuing uncertainty about the U.K.'s standing vis-à-vis the EMA and drug regulation, positions on trade, the EU single market and potential imposition of tariffs on medicines remain completely up in the air. The U.K. government has said it will leave the customs union and the single market while maintaining a close trading relationship, the nature of which remains shrouded in the "strategic ambiguity" surrounding the negotiations.

Pharma and biotech officials, health care professionals and patient advocacy groups across Europe have presented a single voice in making a case for trade in medicines to be the first priority in the second phase of negotiations, highlighting the degree of interdependence across supply chains and the real risk of drug shortages if the U.K. falls outside the EU system. While the EMA appears to be tin-eared, Bates is convinced the unified voice is having an impact with health ministries and the European Commission. (See BioWorld, July 13, 2017, July 18, 2017, and Dec. 12, 2017.)

The U.K.'s life sciences sector also has made access to the best talent a key priority. The conclusion of phase one of the negotiations gave some assurance to EU-27 nationals currently living in the U.K., promising all rights will be maintained. However, questions of future immigration controls and the ease of bringing new recruits into the U.K. remain to be settled. (See BioWorld Today, April 5, 2017, and June 22, 2017.)

If the Brexit timetable is to be met, terms of the divorce need to be agreed by the end of October 2018, giving the European Council, the European Parliament and national governments time to ratify the deal. So with luck, there are only 279 more days of fog and obfuscation to go.


How long does it take a nation to overhaul its outdated regulatory framework, going from a system geared toward generics and me-too drugs to one that encourages risky but more effective new drugs? In China, the answer is about two years. The policy reforms promised by the State Council back in 2015 became a reality in 2017.

In July, the CFDA set the industry abuzz when it agreed to align the country's drug regulations with those of the world's developed markets: the U.S., EU and Japan. By October, the central government issued its "Final Opinion": a comprehensive list of new rules that includes opening up early stage clinical trials to foreign and local players, accepting data packages from overseas clinical trials for market approval and moving to a patent linkage system that protects innovators. (See BioWorld, June 28, 2017, and Oct. 10, 2017.)

Those game-changing regulations were hotly anticipated. But in their absence, Chinese biotechs kept busy strategizing cross-border arrangements to keep momentum. Beigene Ltd., of Beijing, was the year's big winner. The company licensed ex-China rights to its PD-1 candidate in a deal valued at $1.4 billion – the biggest out-licensing deal ever for a domestic firm – to Celgene Corp., of Summit, N.J., and handily took control of Celgene's ready-made China commercial operation to boot. (See BioWorld, July 7, 2017.)

Beigene also is one of a trio of clinical-stage biotechs with unicorn status, obtaining billion dollar-plus valuations after going public on Nasdaq this year, along with Hutchison Medipharma Ltd., or Chi-Med, and Zai Labs Ltd., both of Shanghai (and both sharing the same founder in Samantha Du, currently the CEO of Zai).

This year also saw the CFDA start to make up for lost time. According to a recent McKinsey report, 110 new drug entities were approved to enter the clinic in 2017, up from 88 the year before. Big pharma multinational corporation (MNC) players also are benefiting: as of October, they had 34 drug launches in China compared to just three the year prior. That sense of urgency will help along the 800 innovative molecules said to be in China's pipeline from preclinical to late-stage development.

Peering closer into that pipeline shows that China's fast-follower tendencies are still hard to shake but they are often following in the most promising areas and, as is also frequently the case, looking to leapfrog. China has proved to be a hotbed of development in immuno-oncology, with more than 70 anti-PD-1 or PD-L1 trials and nearly as many CAR T studies underway as in the U.S., although so far none of those agents is CFDA approved.

China could jump ahead in genomics; it has the big data from its large population and analytics from its cheap programmers, along with government support. That promise was reflected in the genomics firm, Wuxi Nextcode Inc., which raised $260 million in September for the biggest venture raise of the year. (See BioWorld, Sept. 11, 2017.)

But with all that optimism, 2018 may bring a late-stage reckoning. Currently, 70 to 80 molecules are in late-stage trials. If any candidates from top firms fail, in the clinic or commercially – as is bound to happen – investors and the government will have their nerves tested and the industry may find its bubble burst. The dark side to China's regulatory reforms is a growing concern that most hospitals lack experience in conducting first-in-human studies and are ill-equipped to handle the influx of trials coming their way. Another challenge is the possibility of a U.S.-China trade war looming on the horizon, which could complicate the plans of leading Chinese biotechs that rely on the U.S. for clinical studies, financing or talent.

Still, China became the world's second-largest drug market with only 30 percent of the drugs that are available in other markets while shackled with an outdated regulatory framework. If all goes according to plan, it shouldn't take long for the country's biopharma industry to zoom ahead.


In May, Keytruda (pembrolizumab, Merck & Co. Inc.) became the first drug to be approved based solely on the presence of a molecular biomarker without regard to tumor location. The tissue-agnostic approval "for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options" was a milestone for both the drug and the FDA. (See BioWorld Today, May 25, 2017.)

Such tumors have extremely high mutational loads, even compared to tumors with other types of DNA repair deficiency, and thus provide a buffet of neoantigens that immune cells can target after being activated by checkpoint blockers.

The approval, and the clinical data it was based on, provided the strongest support yet for the idea that the molecular makeup of tumors can be more important for determining drug response than their anatomical origin. It was also the biggest success to date of so-called basket trials, a relatively new trial design where patients with the same mutation but different anatomical locations are enrolled into the same trial. Loxo Oncology Inc. has also been successful with its basket trial of tropomyosin receptor kinase, or TRK, fusion inhibitor larotrectinib (LOXO-101). (See BioWorld Today, June 7, 2017.)

But overall, much remains to be learned about the relationship between mutation and location. Several other basket trials, including the SUMMIT trial of Puma Biotechnology Inc.'s Nerlynx (neratinib) and a trial of Zelboraf (vemurafenib, Roche Holding AG) in nonmelanoma patients with the V600E mutation have shown that the same driver mutation can respond to the same drug very differently in different anatomical sites.


Platform companies came into their own in 2017, proving that grand promises – often given on behalf of technologies as well as drug candidates in the failure-strewn biotech industry – can become real.

RNA interference-based Alnylam Pharmaceuticals Inc., of Cambridge, Mass., completed at year-end its rolling NDA for patisiran, a candidate targeting transthyretin (TTR) for the treatment of adults with hereditary TTR-mediated amyloidosis. The company asked for priority review and already had won fast track and breakthrough therapy designations from U.S. regulators, along with expanded orphan drug status. Alnylam based its submission on positive phase III data from the 225-patient Apollo phase III study. (See BioWorld, Sept. 21, 2017.)

Another winner in late-stage clinical trials was Ablynx NV, of Ghent, Belgium, which in early October reported positive results from the phase III study of caplacizumab in the treatment of rare blood coagulation disorder acquired thrombotic thrombocytopenic purpura (aTTP). Caplacizumab, which neutralizes the blood glycoprotein von Willebrand factor (vWF), is wholly owned by Ablynx. The company chose aTTP as the in-house route to validating its bispecific nanobody approach, and phase III data demonstrated that by blocking the interaction of vWF precursors with platelets, patients are protected from severe effects while the underlying autoimmune surge resolves. Patients treated with caplacizumab showed a statistically significant reduction in time taken to restore platelet count (p<0.01), and there was a 74 percent reduction in the percentage of patients who suffered either aTTP-related death, recurrence of an episode of aTTP or at least one major thromboembolic event, compared to placebo. (See BioWorld Today, Oct. 3, 2017.)

Notching an approval of an antibody based on its technology was Planegg, Germany-based Morphosys AG, which saw Johnson & Johnson (J&J), of New Brunswick, N.J., win FDA clearance in July for Tremfya (guselkumab) in plaque psoriasis. Although Tremfya moved into a crowded therapeutic space, it was the first approved biologic that selectively blocks interleukin-23. In its second pivotal trial, Tremfya outperformed North Chicago-based Abbvie Inc.'s Humira (adalimumab). Built with Morphosys' Hucal technology, the candidate also delivered significant improvement for patients who had an inadequate response to J&J's Stelara (ustekinumab). (See BioWorld Today, March 6, 2017, and July 14, 2017.)

The liquid biopsy quest made significant news in 2017, too, following the historic approval a year earlier of a blood-based test to detect a gene mutation associated with the most common type of lung cancer as a companion diagnostic for the cancer drug Tarceva (erlotinib, Roche Holding AG). (See BioWorld, Aug. 18, 2017.)

Among the companies active in the field, Menlo Park, Calif.-based Grail Inc. raised more than $900 million in March through the first close of its series B round, putting it on the path to develop a blood-based test for cancer screening. In its series A round, Grail pulled down about $100 million from the likes of Bill Gates, Bezos Expeditions and Sutter Hill Ventures. In May, the company entered a definitive agreement to combine with Cirina Ltd., of Hong Kong, a privately held company also focused on early detection of cancer. (See BioWorld Today, March 2, 2017.)


It was a tale of two halves for shares of biopharmaceutical companies on the capital markets this year. For the first six months of 2017, the BioWorld Biopharmaceutical Index recorded a 9 percent jump in value, but with just a few trading days before year-end the index has recorded a 1 percent drop in value since July. (See BioWorld Today, April 18, 2017, July 10, 2017, and Nov. 7, 2017.)

Despite that prevailing subpar performance, public biopharmaceutical companies had no difficulty attracting capital. In fact, the total raised from follow-on financings and IPOs, at $31.5 billion, ranks second all time behind the almost $50 billion raised by global biopharmas during 2015. It has also been a successful year for the biotech IPO market. After coming off a slow third quarter, where 10 biopharma companies completed their IPOs in the U.S., collectively raising just over $1 billion, the market picked up again. Approaching the end of the fourth quarter, 12 biopharma companies have graduated to the public ranks on U.S. exchanges, collectively raising more than $1.2 billion. That brings the total of 2017 U.S. biotech IPOs to 41, with $4.2 billion generated. (See BioWorld, July 17, 2017, and Dec. 5, 2017.)

Private financings also went on a tear. The $10.5 billion raised established a record for the industry, eclipsing the previous 2015 record of $10.3 billion. (See BioWorld Today, May 12, 2017.)

In all, the biopharma industry raised a massive $51 billion in 2017 – well short of the almost $69 billion that was raised in 2015 but a total that firmly places it in second place in terms of totals raised. In the past five years the global biopharma industry has generated $216 billion from its fundraising activities.


Just a few short years ago, the prospect of therapeutic applications of human germline editing seemed remote. Even if the scientific and technological barriers to engineering early stage embryos or gametes have been falling, there remained a sense, at least among the vast majority of scientists who conform to the ethical norms of their trade, that germline editing was strictly verboten.

But everything changed in 2017. In February, the U.S. National Academies of Sciences and Medicine published an authoritative report, Human Genome Editing: Science, Ethics, and Governance, which reset the terms of the debate. Scientists now have permission – even if it's highly qualified and couched in highly cautious language – to start thinking the unthinkable. Although it's still quite some distance from human clinical trials, engineering the human genome is now on the agenda, and the means of doing so is increasingly evident. (See BioWorld Today, Feb. 15, 2017.)


No list of the top biopharma stories for 2017 would be complete without mentioning the havoc drug companies suffered in the wake of hurricanes and a cyberattack. Hurricane Harvey and the extensive flooding that followed it temporarily interrupted biomedical research in Texas shortly before Irma and Maria slammed into Puerto Rico. With the island's power, communication, water and transportation systems crippled by the hurricanes, Puerto Rico's drug manufacturing industry struggled with backup generators to maintain some production and protect inventories. More than 300 clinical trials were affected by the hurricanes, and the FDA worked with the biopharma industry to address shortages caused by the extended devastation. (See BioWorld, Sept. 27, 2017.)

A global cyberattack in June disrupted Merck & Co. Inc.'s worldwide operations, including manufacturing, research and sales. The Notpetya malware attack forced the Kenilworth, N.J., company to prioritize production of medicines and vaccines considered life-saving or medically significant while it spent several months bringing its systems back online.

As a result of the hurricane damage and the cyberattack, industry players, regulators and relief agencies began to rethink security, contingency plans and relief efforts.

BioWorld staffers Anette Breindl, Shannon Ellis, Michael Fitzhugh, Nuala Moran, Randy Osborne, Marie Powers, Mari Serebrov, Cormac Sheridan and Peter Winter contributed to this report.

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