Following two consecutive years of high numbers in new molecular entity (NME) approvals by the US Food and Drug Administration’s Center for Drug Evaluation and Research, NME approvals in 2016 dropped to a six-year low. So what drugs passed regulatory hurdles and what are their market potential?

In 2016, the number of NME approvals fell to 22 (which includes 20 drugs and two radioactive diagnostic imaging agents) from the 45 NMEs approved in 2015, a recent high. In the mix between biologics and small-molecule drugs NME approvals, the percentage of NME approvals for biologics relative to overall NME approvals reached a recent high at 32% of all NMEs approved in 2016. Among the major pharmaceutical companies, Roche, Eli Lilly and Company, Merck & Co., and Biogen led with two NME approvals each.

2016 NME approvals slow
In 2016, the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) approved 22 NMEs (see Table I at end of article), which was a 51% drop compared with the 45 NMEs approved in 2015 and the lowest total on NME approvals since 2010 when 21 NMEs were approved (see Table II). From 2011 to 2015, NME approvals had been on an upward trajectory (with the exception of 2013) with 30 NMEs approved in 2011 and 39 in 2012. The exception was in 2013, which had a decline to 27 NMEs, but levels jumped again to 41 NMEs in 2014 and peaked at a recent high of 45 approvals in 2015 (see Table II).

On a molecule basis, the 22 NME approvals in 2016 consisted of 13 small-molecule drugs, seven biologics, and two radioactive diagnostic imaging agents (see Tables I [at end of article] and II). The percentage of biologic-based drugs approved relative to all NME approvals reached a recent high in 2016, accounting for 32% of all NMEs approved, compared to the prior two years in which biologics accounted for 27% of total NME approvals in 2014 and 2015. (see Table II). With the approval of the seven biologics and two radioactive diagnostic imaging agents in 2016, the percentage of small-molecule drug NME approvals hit a recent low in 2016, accounting for 59% of total NME approvals. The recent high was in 2013 when 81% of NME approvals were small molecules. (see Table II).

In 2016, the large pharmaceutical companies accounted for 13 of the 22 NME approvals, which included eight small-molecule drugs and six biologics. Smaller companies accounted for the remaining eight NME approvals in 2016, which included five small-molecule drugs, one biologic, and two radioactive diagnostic imaging agents.

Of the 13 small-molecule drugs approved as NMEs in 2016, the large pharmaceutical companies accounted for eight small-molecule NME approvals (see Table III), and other companies accounted for five NME approvals.The small-molecule drug NME approvals in 2016 by the large pharma companies were: AbbVie/Roche’s Venclexta (venetoclax), a drug to treat leukemia; Biogen’s Spinraza (nusinersen), a drug for treating the rare disease of spinal muscular atrophy; Gilead Sciences’ Epclusa (sofosbuvir and velpatasvir), a combination hepatitis C drug; Merck & Co.’s Zepatier (elbasvir and grazoprevir), a combination hepatitis C drug; Pfizer’s Eucrisa (crisaborole), a drug to treat eczema; Sanofi’s Adlyxin (lixisenatide), a drug to treat Type II diabetest; Shire’s Xiidra (lifitegrast ophthalmic solution), a drug to treat dry-eye disease; and UCB’s Briviact (brivaracetam), an anti-epilepsy drug (see Table III).

Smaller companies accounted for the remaining five small-molecule NME approvals in 2016 (see Table III). The five small-molecule NME approvals in 2016 by smaller companies were: Acadia Pharmaceuticals’ Nuplazid (pimavanserin), a drug for treating symptoms of psychosis of Parkinson’s disease; Clovis Oncology’s Rubraca (rucaparib) for treating ovarian cancer; Intercept Pharmaceuticals’ Ocaliva (obeticholic acid), a liver-disease drug; Jazz Pharmaceuticals’ Defitelio (defibrotide) for treating liver conditions following hematopoietic stem-cell transplantation; and Sarepta Therapeutics’ Exondys (eteplirsen), for treating a genetic muscle disorder (see Table III). .

In addition to the small-molecule drugs, two smaller companies received NME approvals for radioactive diagnostic imaging agents: Advanced Accelerator Applications’ Netspot (gallium Ga 68 dotatate injection) and Blue Earth’s Axumin (fluciclovine F 18) (see Table I at end of article).

On the biologics side, the large pharmaceutical companies accounted for six NME approvals in 2016 and smaller companies one NME approval (see Table IV). The six biologics approved as NMEs from the large pharmaceutical companies were: Biogen’s Zinbryta (daclizumab), a multiple sclerosis drug; two biologics from Eli Lilly and Company—Lartruvo (olaratumab) for treating soft-tissue sarcoma and Taltz (ixekizumab), a psoriasis drug—; Merck & Co.’s Zinplava (bezlotoxumab), an anti-infective; Roche’s Tecentriq (atezolizumab) for treating bladder cancer; and Teva Pharmaceutical Industries’ Cinqair (reslizumab), an anti-asthma drug (see Table IV).

One smaller company had a biologic NME approved in 2016, which was Anthim (obiltoxaximab), an anti-anthrax drug by Elusys Therapeutics, a Pine Brook, New Jersey-based biopharmaceutical company focused on infectious diseases.

Roche, Lilly, Merck & Co., and Biogen lead 2016 NME approvals
Among the pharmaceutical majors, Roche, Lilly, Merck & Co., and Biogen led the pack in 2016 NME approvals with each company having two NME approvals, with some projected by some analysts for blockbuster status.

Roche. Roche scored two NME approvals in 2016: Tecentriq (atezolizumab), an anti-bladder-cancer drug, and Venclexta (venetoclax), a drug for treating chronic lymphocytic leukemia. Tecentriq, a programmed death (PD)-1/PD-L1 inhibitor, is the first (PD)-1/PD-L1 inhibitor to be approved for urothelial carcinoma, the most common type of bladder cancer, according to the FDA. Tecentriq represents Roche’s first commercial entry for a PD-1/PD-L1 inhibitor, an important new class of immuno-oncology drugs, and is forecast by some analysts to reach blockbuster status. In January 2017, the FDA accepted a supplemental biologics license application from Roche for an additional indication for Tecentriq for treating a certain type of advanced bladder cancer and also granted priority review for this indication.

Tecentriq will join the two leading commercial  (PD)-1/PD-L1 inhibitors, which are indicated for other types of cancer: Bristol-Myers Squibb’s Opdivo (nivolumab) and Merck & Co.’s Keytruda (pembrolizumab). Some analysts project that Opdivo and Keytruda, which respectively had 2015 sales of $942 million and $566 million, will reach blockbuster status. Other late-stage (PD)-1/PD-L1  inhibitors by pharmaceutical majors include Merck KGaA’s avelumab and AstraZeneca’s durvalumab, which is also being developed to treat bladder cancer

The other NME approval by Roche in 2016 drug was Venclexta, which is also pegged by some analysts for blockbuster status. The drug is manufactured by AbbVie and jointly commercialized in the US by AbbVie and Roche, through its Genentech subsidiary. AbbVie is commercializing the drug outside the US.

Lilly. Lilly received two NME approvals in 2016, both biologics: Taltz (ixekizumab), for treating moderate-to-severe plaque psoriasis, and Lartruvo (olaratumab), for treating certain types of soft tissue sarcoma in combination with another anti-cancer drug, doxorubicin. Taltz joins Amgen’s Enbrel (etanercept) and AbbVie’s Humira (adalimumab), both blockbuster drugs for the same indication. Enbrel, which is marketed by Amgen in the US and Canada and by Pfizer outside of those regions, had 2015 sales of $5.36 billion for Amgen in the US and Canada and sales of $3.33 billion for Pfizer outside the US and Canada. AbbVie’s Humira had 2015 global sales of $14 billion. Lartruvo join Lilly’s oncology franchise, which had $3.5 billion in 2015 sales.

Merck & Co. Merch & Co. received two NME approvals in 2016: Zepatier (elbasvir and grazoprevir), a small-molecule combination drug regimen for treating hepatitis C, and Zinplava (bezlotoxumab), an anti-bacterial biologic for treating Clostridium difficile infection. Zepatier is a contender in the hepatitis C market, which had another NME approval in 2016: Gilead’s hepatitis C combination drug, Epclusa (sofosbuvir and velpatasvir). These drugs join other drugs to treat hepatitis C: Gilead’s Sovaldi, which posted 2015 sales of $5.3 billion, and Gilead’s Harvoni (sofosbuvir and ledipasvir), which had 2015 sales of $13.9 billion. Other competitors among the large pharmaceutical companies in the hepatitis C market include: AbbVie’s Technivie (ombitasvir, paritaprevir and ritonavir), which is approved for use in combination with ribavirin for treating hepatitis C virus (HCV), AbbVie’s Viekira Pak (veruprevir, ritonavir, ombitasvir, and dasabuvir), an all-oral regime, and Bristol-Myers Squibb’s Daklinza (daclatasvir) for use with sofosbuvir to treat hepatitis C virus genotype 3 infections.

The other NME approval in 2016 for Merck & Co. was Zinplava, which joins Merck’s anti-infectives portfolio. Bezlotoxumab was developed by researchers at the University of Massachusetts Medical School’s MassBiologics Laboratory in conjunction with Medarex (now part of Bristol-Myers Squibb) and was licensed to Merck & Co. in 2009.

Biogen. Biogen received two NME approvals in 2016: Spinraza (nusinersen), a small-molecule drug for treating the rare disease of spinal muscular atrophy (SMA), and Zinbryta (daclizumab), a biologic for treating multiple sclerosis. Biogen is partnered with Ionis Pharmaceuticals, a Carlsbad, California-based pharmaceutical company, for Spinraza. Biogen teamed with Ionis (formerly Isis Pharmaceuticals) in 2012 to develop Spinraza in a deal worth $299 million. Spinraza is projected by some analysts to be a blockbuster drug as it is approved for use across a range of SMA patients and is the first drug approved for this rare genetic disease, according to the FDA.

For Zinbryta, Biogen is sharing co-promotion activities with AbbVie in the US, European Union, and Canada. Biogen is solely responsible for commercialization of the drug in the rest of the world. Biogen is responsible for manufacturing and research and development activities. Zinbryta joins Biogen’s multiple sclerosis franchise, which is the company’s leading product area, which had 2015 revenues of $8.58 billion, representing 93% of the company’s total revenues.

Other 2016 NME approvals by pharma majors
Other pharmaceutical majors that scored NME approvals by FDA’s CDER in 2016 were Pfizer, Sanofi, Gilead Sciences, Shire, Teva Pharmaceutical Industries, and UCB, with some of these drugs with blockbuster potential, according to analysts. 

Pfizer received approval for Eucrisa (crisaborole), a small-molecule drug for treating eczema. Some analysts expect that Eucrisa will have blockbuster status. Pfizer gained the drug through its $5.2 billion-acquisition of Anacor Pharmaceuticals in 2016.

Sanofi received approval for its small-molecule anti-diabetes drug, Adlyxin (lixisenatide) for improving glycemic control in patients with Type II diabetes. The drug is an addition to the company’s diabetes franchise, which is the company’s leading product area with 2015 revenues of EUR 7.58 billion ($8.03 billion). Sanofi’s diabetes franchise has been facing generic competition for its top-selling product, Lantus (insulin-glargine), which had 2015 sales of EUR 6.39 billion ($6.77 billion). Adlyxin is a glucagon-like peptide-1 (GLP-1) receptor agonist, which is a hormone that helps normalize blood sugar levels. Adlyxin will join other GLP-1 receptor agonists already on the market, which include Novo Nordisk’s Victoza (liraglutide recombinant) and Lilly’s Trulicity (dulaglutide). Victoza and Trulicity had 2015 sales of DKK 18 billion ($2.56 billion) and $248 million, respectively.

Gilead Sciences received FDA approval for a new combination hepatitis C drug, Epclusa (sofosbuvir and velpatasvir), an all-oral, pan-genotypic, single tablet regimen for treating a broad genotype range of chronic HCV infection, and is poised by some analysts for blockbuster status. The drug had sales of $640 million in the third quarter of 2016, its first full quarter on the market. Epclusa uses the active ingredient, sofosbuvir, also the active ingredient in Gilead’s blockbuster HCV drug, Sovaldi, which posted 2015 sales of $5.3 billion. Sofosbuvir is also a key ingredient in Gilead’s other combination HCV therapy, Harvoni (ledipasvir and sofosbuvir), another blockbuster drug that posted 2015 sales of $13.9 billion.

Other large pharma companies that received NME approvals in 2016 were Shire, Teva, and UCB. Shire received approval for Xiidra (lifitegrast ophthalmic solution), a small-molecule drug for treating dry-eye disease. Some analysts have pegged Xiidra to be a potential blockbuster. Xiidra is expected to compete with Allergan’s dry-eye disease product, Restasis (cyclosporine ophthalmic emulsion), which had 2015 sales of approximately $1.05 billion. Teva received an NME approval for a biologic, Cinqair (reslizumab), to treat severe asthma, and UCB received approval for Briviact (brivaracetam), a small-molecule drug for treating epilepsy.

NME approvals by other companies
Smaller companies accounted for the remaining six NMEs approved in 2016, which includes five small-molecule drugs and one biologic.

 The remaining five small-molecule drug NME approvals in 2016 were: Clovis Oncology’s Rubraca (rucaparib), a poly ADP-ribose polymerase (PARP) inhibitor for treating ovarian cancer; Intercept Pharmaceuticals’ Ocaliva (obeticholic acid) for treating a rare, chronic liver disease known as primary biliary cholangitis in combination with a bile acid; Sarepta Therapeutics’ Exondys 51 (eteplirsen) for treating Duchenne muscular dystrophy, a rare genetic disorder; Jazz Pharmaceuticals’ Defitelio (defibrotide sodium) for treating hepatic veno-occlusive disease in patients following a stem-cell transplant from blood or bone marrow; and Acadia Pharmaceuticals’ Nuplazid (pimavanserin), for treating hallucinations and delusions experienced by some patients with Parkinson’s disease.

The one biologic approved by a smaller company was Elusys Therapeutics’ Anthim (obiltoxaximab), a monoclonal antibody for treating a rare disease, inhalation anthrax, in combination with other appropriate anti-bacterial drugs.