Market Watch: Parenteral Drugs on the Rise

By Patricia Van Arnum - DCAT Editorial Director

February 1, 2017

With the rise of biologic-based drug development, the number of parenteral drugs under development and receiving approval is poised to increase, so what do the numbers show?.

Parenteral drugs, whether a small-molecule or biologic-based drug substance, has increased their share of the overall drug market although solid-dosage products still prevail. DCAT Value Chain Insights examines recent approvals of new molecular entities to see which parenteral drugs are making the mark

New molecular approvals in 2016.
In 2016, the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) approved 22 new molecular entities (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) (1).

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) (1). 

Table II: Small Molecule and Biologics New Molecular Entities Approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research, 2010 to 2016.
Year Number of New Molecular Entities (NMEs) Approved Percentage relative to total NME approvals and number of small molecules and biologics approved as NMEs
2010 21 NMEs approved 71% small molecules (15 NMEs)
29% biologics (6 NMEs)
2011 30 NMEs approved

77% small molecules (23 NMEs) 
20% biologics (6 NMEs)
Plus 1 NME radioactive diagnostic imaging agent)*

2012 39 NMEs approved

79% small molecules (31 NMEs)
15% biologics (6 NMEs)
Plus 2 NME radioactive diagnostic imaging agents)**

2013 27 NMEs approved

81% small molecules (22 NMEs) 
11% biologics (3 NMEs)
Plus 2 NME radioactive imaging agents)***

2014 41 NMEs approved

71% small molecules (29 NMEs)
27% biologics (11 NMEs)
Plus 1 NME radioactive diagnostic imaging agent)****

2015     45 NMEs approved* 71% small molecules (32 NMEs) and 1 insulin analog NME approved as a new drug application)*****
27% biologics (12 NMEs)
2016 22 NMEs approved**

59% small molecules (13 NMEs)
32% biologics (7 NMEs)
Plus 2 NME radioactive diagnostic imaging agents)******

*In 2011, 23 small-molecule drugs and 1 radioactive diagnostic imaging were approved as new drug applications (NDAs)
**In 2012, 31 small-molecule drugs and 2 radioactive diagnostic imaging agents were approved as NDAs
***In 2013, 22 small-molecule drugs and 2 radioactive diagnostic imaging agents were approved as NDAs
****In 2014, 29 small-molecule drugs and 1 radioactive diagnostic imaging agent were approved as NDAs
*****In 2015, 32 small-molecule drugs were approved as NDAs and one insulin analog, Novo Nordisk's Tresiba (insulin degludec injection), a long-acting basal human insulin analog produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification was approved as a NDA, not as a biologics license application.
******In 2016, 13 small-molecule drugs and 2 diagnostic imaging agents were approved as NDAs.

Source: US Food and Drug Administration's Center for Drug Evaluation and Research and company information.


Of these 22 NME approvals, 13, or 59%, of the NMEs approved, were parenterals (11 parenteral drugs and two diagnostic agents), seven, or 32%, were oral drugs, and two or 8% were other (one a topical drug and one;ophthalmic; (see Table I at the end of article). Among the large pharmaceutical drugs, the parenteral drugs approved as NMEs in 2016 were: Biogen’s Spinraza (nusinersen), a drug for treating the rare disease of spinal muscular atrophy; Biogen’s Zinbryta (daclizumab), a multiple sclerosis drug; Eli Lilly and Company’s Taltz (ixekizumab) for treating moderate-to-severe plaque psoriasis; Lilly’s Lartruvo (olaratumab) for treating certain types of soft tissue sarcoma; Merck & Co.s Zinplava (bezlotoxumab), an anti-bacterial biologic for treating Clostridium difficile infection; Roche's Tecentriq (atezolizumab), an anti-bladder-cancer drug; Sanofi’s Adlyxin (lixisenatide) for improving glycemic control in patients with Type II diabetes; and Teva’s Cinqair (reslizumab) for treating severe asthma;

Biogen received two NME approvals in 2016 that were parenteral drugs: 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 (1).

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.

Lilly received two NME approvals in 2016, both biologic-based parenterals: 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 2016 global sales of $16 billion. Lartruvo join Lilly’s oncology franchise, which had $3.5 billion in 2015 sales (1).

Zinplava 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 (1).

Roche’s Tecentriq represents the company’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 (1).

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 (1).

Reference
1. F. Mirasol, “2016 NME Drug Approvals Drop After Recent High,”DCAT Value Chain Insights (January 2017).

Table I: 2016 New Molecular Entities (New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) Approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research.
Company Property name (active ingredient); application type Indication Dosage form; route of administration
AbbVie and Roche* Venclexta (venetoclax); NDA Chronic lymphocytic leukemia in patients with a specific chromosomal abnormality Tablet; oral
Acadia Pharmaceuticals Nuplazid (pimavanserin); NDA Hallucinations and delusions associated with psychosis experienced by some people with Parkinson’s disease Tablet; oral
Advanced Accelerator Applications Netspot (gallium Ga 68 dotatate injection); NDA Diagnostic imaging agent to detect rare neuroendocrine tumors Powder; intravenous
Biogen** Spinraza (nusinersen); NDA Spinal muscular atrophy Solution; intrathecal
Biogen Zinbryta (daclizumab); BLA Multiple sclerosis Injectable;injection
Blue Earth Axumin (fluciclovine F 18); NDA Diagnostic imaging agent to detect recurrent prostate cancer Solution; intravenous
Clovis Oncology Rubraca (rucaparib); NDA Certain types of ovarian cancer Tablet; oral
Eli Lilly and Company Lartruvo (olaratumab); BLA Certain types of soft tissue sarcoma Injectable;injection
Eli Lilly and Company Taltz (ixekizumab); BLA Moderate-to-severe plaque psoriasis Injectable;injection
Elusys Therapeutics Anthim (obiltoxaximab); BLA Inhalational anthrax in combination with appropriate antibacterial drugs Injectable;injection
Gilead Sciences Epclusa (sofosbuvir and velpatasvir); NDA All six major forms of hepatitis C virus Tablet; oral
Intercept Pharmaceuticals Ocaliva (obeticholic acid); NDA Rare, chronic liver disease Tablet; oral
Jazz Pharmaceuticals*** Defitelio (defibrotide sodium); NDA Hepatic veno-occlusive disease Solution; IV (infusion)
Merck & Co. Zepatier (elbasvir and grazoprevir); NDA Chronic hepatitis C virus, genotypes 1 and 4 Tablet; oral
Merck & Co. Zinplava (bezlotoxumab); BLA Clostridium difficile infection for patients 18 years of age or older Injectable;injection
Pfizer**** Eucrisa (crisaborole); NDA Mild-to-moderate eczema (atopic dermatitis) for patients two years of age and older Ointment; topical
Roche Tecentriq (atezolizumab) BLA Urothelial carcinoma, the most common type of bladder cancer Injectable;injection
Sanofi Adlyxin (lixisenatide); NDA Type 2 diabetes for improving blood-sugar levels Solution; 

subcutaneous

Sarepta Therapeutics Exondys 51 (eteplirsen); NDA Duchenne muscular dystrophy Solution; iV (infusion)
Shire Xiidra (lifitegrast ophthalmic solution); NDA Dry-eye disease Solution/drops; ophthalmic
Teva Pharmaceuticals Cinqair (reslizumab); BLA Severe asthma Injectable; injection
UCB Briviact (brivaracetam); NDA; Partial onset seizures in patients age 16 years and older with epileps Tablet; oral

* Venclexta (venetoclax) is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the US and commercialized by AbbVie outside of the US.
** Spinraza (nusinersen) is marketed by Biogen and was developed by Ionis Pharmaceuticals of Carlsbad, California.
*** Jazz Pharmaceuticals acquired Gentium in 2014 and with it, Defitelio (defibrotide sodium).
**** Pfizer acquired Anacor Pharmaceuticals in 2016, and with it, Eucrisa (crisaborole).

Source: US Food and Drug Administration's Center for Drug Evaluation and Research and company information.