Another year, another round of approvals, mixed reviews and high-profile failures. We look back on which medicines made the headlines.
In November, the US Food and Drug Administration (FDA) approved the first oral disease-modifying drug for rheumatoid arthritis in more than a decade. Pfizer’s twice-daily pill—which works by blocking enzymes, called Janus kinases, that are involved in joint inflammation—is also being tested as a treatment for psoriasis, colitis and other diseases.
A new class of agents directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism, is moving into the last stage of clinical development. In phase 2 trials reported this year, experimental PCSK9 inhibitors from Amgen, Pfizer and Regeneron Pharmaceuticals (in partnership with Sanofi) each reduced low-density lipoprotein levels by 40–60%, on average, in various patient populations.
The first drug designed to treat the underlying cause of cystic fibrosis won approval in 2012 from both European and US regulators. Although the approved therapy will only benefit those 4% of cystic fibrosis sufferers who have a specific genetic defect known as the G551D mutation, Vertex Pharmaceuticals reported interim data this year showing that the drug, marketed as Kalydeco, helped improve lung function in people with the most common mutation associated with the disease when administered in combination with an experimental agent called VX-809.
European regulators in November approved the first gene therapy product to be used in the Western world. UniQure’s Glybera relies on an adeno-associated viral vector to deliver a functional copy of the gene that is deficient in individuals with a rare lipid-processing disease called lipoprotein lipase deficiency, which affects around one in a million people worldwide.
Aubagio (teriflunomide) and BG-12 (dimethyl fumarate)
People with multiple sclerosis now have a second oral drug option—and a third could be just around the corner. In September, the FDA approved Sanofi’s once-a-day tablet Aubagio for the treatment of relapsing forms of the disease. A week later, Biogen Idec posted positive phase 3 trial data for its own oral agent, BG-12. Both pills face competition from Novartis’s Gilenya (fingolimod), which hit the market in 2010.
T-DM1 (trastuzumab emtansine)
In November, the FDA granted priority-review designation to an antibody-drug conjugate developed in a partnership between Roche and ImmunoGen. Earlier in the year, phase 3 data showed that the therapy—a combination of the monoclonal antibody Herceptin (trastuzumab) linked to the cytotoxic agent mertansine—prolonged median survival by about six months longer than standard therapy did among women with advanced HER2-positive breast cancer.
Truvada (enofovir/emtricitabine) and Stribild
Gilead’s combination antiretroviral pill Truvada received the blessing of US authorities in July as a strategy for reducing the risk of HIV infection among adults at high risk of sexually acquired infection. A month later, Gilead scored another FDA blessing for its four-in-one drug Stribild, which packages Truvada together with two newer ingredients, elvitegravir and cobicistat, to combat the virus in HIV-positive individuals who have not received prior treatment.
In July, Merck announced an early close to a 16,000-person clinical trial of odanacatib after a review of early results reportedly showed that the experimental osteoporosis drug significantly reduced the risk of bone fractures among post-menopausal women. Phase 2 data released this year similarly demonstrated that the investigational cathepsin K inhibitor increased bone mineral density by significantly more than standard therapy. Merck plans to file for regulatory approval early next year.
Elelyso (taliglucerase alfa)
The first pharmaceutical manufactured using genetically engineered plant cells, an enzyme replacement therapy for the treatment of Gaucher’s disease from Protalix BioTherapeutics and Pfizer, won approval this year from regulators in both the US and Israel. Yet the European Medicines Agency (EMA) rejected the drug in November because a competing agent from Shire has orphan market exclusivity in the EU until 2020.
Belviq (lorcaserin) and Qsymia (phentermine/topiramate)
For the first time in over a decade, the FDA approved new weight-loss pills: Belviq, a serotonin receptor activator from Arena Pharmaceuticals and Eisai, and Qsymia, a combination of an appetite suppressant and an anticonvulsant from Vivus. Across the Atlantic, however, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended against approving Vivus’s agent, citing potential cardiovascular and central nervous system effects. Analysts expect a similar negative decision from the European panel regarding Belviq.
In May, Roche announced plans to discontinue development of its cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib after an interim review of the company’s phase 3 trial failed to show any signs of clinically meaningful efficacy. Pfizer similarly pulled the plug on its own CETP blocker torcetrapib in 2006. But others are forging ahead with drugs in the same class, which are all designed to raise levels of so-called ‘good’ cholesterol or high-density lipoprotein. For example, Merck’s anacetrapib and Eli Lilly’s evacetrapib are still in active development.
The world’s most advanced vaccine against dengue fever proved safe and 60–90% effective against three of the four genetic forms of the dengue virus, scientists reported in September. However, in the trial of 4,000 schoolchildren in Thailand, the Sanofi product offered no protection from the most common dengue strain circulating in the country at the time.
Tresiba (insulin degludec) and Ryzodeg (insulin degludec/insulin aspart)
Novo Nordisk’s ultra-long-acting insulins, Tresiba and Ryzodeg, won approval from Japanese regulators and received positive reviews from Europe’s CHMP and an FDA advisory committee this year. Both basal insulin analogs, one of which also includes a bolus insulin boost, have been shown to reduce rates of severe hypoglycemia. However, they have also been linked to an increased risk of heart disease, which led the FDA panel to vote unanimously in favor of Novo conducting further cardiovascular outcome studies.
Vyndaqel (tafamidis meglumine)
The FDA rejected Pfizer’s rare-disease drug in June and asked for another trial to demonstrate that the selective stabilizer of the transthyretin protein helps patients with a neurodegenerative disease known as transthyretin familial amyloid polyneuropathy, which affects an estimated 8,000 people worldwide. European regulators had previously approved the drug in November 2011.
Injury lawsuits began to mount this year against Boehringer Ingelheim’s blood thinner Pradaxa (dabigatran), although the FDA said in November that rates of gastrointestinal bleeding and brain hemorrhage were no higher in people taking the drug than in those on warfarin. Meanwhile, Xarelto (rivaroxaban), marketed by Johnson & Johnson and Bayer and approved since 2011 for stroke prevention, can now be used to prevent blood clots in the legs and lungs, but not to treat acute coronary syndrome, the FDA ruled this year. All the while, Pfizer and Bristol-Myers Squibb are still awaiting a regulatory decision from the FDA on Eliquis (apixaban), which was twice delayed and is now expected in March 2013.
Bristol-Myers Squibb halted development of this hepatitis C drug in August after a trial participant died of heart failure following drug administration. The company acquired the nucleotide polymerase inhibitor just seven months earlier in a $2.5 billion buyout of Inhibitex. The discontinued agent was estimated to make up around 70% of Inhibitix’s total value.
Bapineuzumab and solanezumab
Two antibody drugs designed to target the amyloid-β plaques in the brains of people with Alzheimer’s disease both flunked in late-stage trials this year. Neither bapineuzumab nor solanezumab significantly slowed overall cognitive and functional decline in study subjects with the neurodegenerative disease. Johnson & Johnson and Pfizer halted development of bapineuzumab. Eli Lilly spun the news on solanezumab favorably by touting a secondary analysis that hinted that the drug might help with milder forms of the condition.
A kinase inhibitor designed to target the tau deposits associated with Alzheimer’s disease also flopped this year. In a 306-person, phase 2 study, tideglusib, a glycogen synthase kinase 3 inhibitor from Madrid-based Noscira, failed to improve cognitive decline or meet other secondary trial endpoints after six months of treatment in people with mild-to-moderate forms of the disease.
In October, doctors involved in testing a new chronic kidney disease therapy from Abbott Laboratories and Reata Pharmaceuticals received an email telling them to contact their patients and tell them to stop taking the drug. The trial stoppage came after an independent monitoring committee had linked bardoxolone—which protects against oxidant and inflammatory stress by inducing the nuclear factor (erythroid-derived 2)-like 2 pathway—to a high rate of serious side effects, including death.
AstraZeneca’s and BTG’s experimental sepsis agent became the latest in a long line of drugs to prove no better than placebo in human testing. In a 300-person study announced in August, the tumor necrosis factor-α–targeting antibody did not yield improvements in ventilator-free days, the primary endpoint, or in other measures such as mortality. The companies ceased further development.
A version of this article appears in the December print issue of Nature Medicine.