Parenteral Drugs: Tracking New Drug Approvals

By Patricia Van Arnum - DCAT Editorial Director

November 8, 2017

With the rise of increasingly complex active pharmaceutical ingredients (APIs), specifically biologics and poorly soluble small molecules, the number of parenteral drugs increases as well. Over the past three years, the percentage of parenteral new molecular entities approved by the FDA has increased. DCAT Value Chain Insights examines trends for parenteral drugs.

Parenteral drugs, which are administered by non-oral means, such as through injection or infusion, may be a small molecule or biologic. Increases in parenteral drug development is important for related manufacturing services and ingredients, such as excipients, used to develop and produce these drugs. DCAT Value Chain Insights looks at recent trends in parenteral-drug approvals.

Parenteral drugs: examining recent drug approvals

Parenteral drugs refer to drugs using non-oral means of administration by injecting the drug directly into the body typically through three common routes of administration: intramuscular, subcutaneous and intravenous.The percentage of parenteral drugs approved as new molecular entities (NMEs) by the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) has increased over the last three years.

Of the 22 NMEs approved in 2016, 11 or 50% were parenteral drugs. In 2015, 20 or 44% of the total 45 NME approvals were parenteral drugs, and in 2014, 16 or 39% of the total 41 NMEs approved were parenterals. Of the 35 NMEs approved as of October 31, 2017, 14 or 40% were parenteral drugs. (see Table I ).

Table I. Number of Parenteral Drugs in Relation to Total New Molecular Entity (NME) Approvals, 2014 to 2016, and 2017 to date (as of Oct. 31, 2017)
Year span> Number of New Molecular Entities (NMEs) Approved Number of parenteral drugs approved as new molecular entities Percentage of parenteral drugs approved as new molecular entities
2017 (as of Oct. 31, 2017) 35 NMEs approved 14 NME parenteral drugs approved 40%
2016 22 NMEs approved 11 NME parenteral drugs approved 50%
2015 45 NMEs approved 20 NME parenteral drugs approved 44%
2014 41 NMEs approved 16 NME parenteral drugs approved 39%

Note: Of the 22 new molecular entity approvals in 2016, 20 were for drugs (small molecules and biologics) and two NMEs were for radioactive diagnostic imaging agents. 

Note: Of the 41 NMEs approved in 2014, 40 were for drugs (small molecules and biologics) and one NME was a radioactive diagnostic imaging agent.

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

Parenteral drug approvals: 2017 to date

The large and/or mid-tier pharmaceutical companies have accounted for 10 of the 14 parenteral NMEs approved thus far in 2017. These include: Amgen’s Parsabiv (etelcalcetide) for treating secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis; AstraZeneca’s Imfinzi (durvalumab) for treating locally advanced or metastatic urothelial carcinoma (bladder cancer); Bayer’s Aliqopa (copanlisib) for treating relapsed follicular lymphoma; Johnson & Johnson’s (Janssen Biotech) Tremfya (guselkumab for treating moderate-to-severe plaque psoriasis; Merck KGaA’s and Pfizer’s Bavencio (avelumab) for treating metastatic Merkel cell carcinoma (a rare form of skin cancer); Mitsubishi Tanabe Pharma America’s Radicava (edaravone) for treating amyotrophic lateral sclerosis (i.e, Lou Gehrig’s disease); Roche’s Ocrevus (ocrelizumab) for treating relapsing forms of multiple sclerosis and primary progressive multiple sclerosis; Sanofi’s and Regeneron Pharmaceuticals’ Dupixent (dupilumab) for treating moderate-to-severe eczema; Sanofi’s Kevzara (sarilumab for treating rheumatoid arthritis); and Valeant Pharmaceuticals’ Siliq (brodalumab) for treating moderate-to-severe plaque psoriasis (see Table II at end of article).

Smaller pharmaceutical companies accounted for the remaining four parenteral drugs approved as NMEs thus far in 2017. These include: BioMarin Pharmaceutical’s Brineura (cerliponase alfa) for treating a specific form of Batten disease; Melinta Therapeutics’ Baxdela (delafloxacin) for treating acute bacterial skin infections (note: an oral formulation was also approved); Radius Health’s Tymlos (abaloparatide) for treating osteoporosis; and The Medicines Company’s Vabomere (meropenem and vaborbactam) for treating complicated urinary tract infections (see Table II at end of article).

Parenteral drug approvals: 2016

The large pharmaceutical companies accounted for the majority of new parenteral drug approvals over the past several years. Eight of the 11 parenteral drugs approved in 2016 were by leading pharma companies, and three were from smaller companies. In 2015, 12 of the 20 parenteral drugs approved were from major pharma companies, and eight were from smaller companies. For 2014 parenteral drug approvals, nine were from major pharma companies and seven were from smaller companies.

In 2016, major pharma companies led with eight parenteral drugs approvals. These drugs included: Biogen’s Spinraza (nusinersen sodium) for treating muscular atrophy and Zinbryta (daclizumab), a multiple sclerosis drug; Eli Lilly and Company’s Lartruvo (olaratumab) for treating soft-tissue sarcoma, and Taltz (ixekizumab) for treating moderate-to-severe plaque psoriasis; Merck & Co.’s Zinplava (bezlotoxumab) for treating Clostridium difficile infection; Roche’s Tecentriq (atezolizumab), a bladder-cancer drug; Sanofi’s Adlyxin (lixisenatide), a diabetes drug; and Teva Pharmaceutical Industries’ Cinqair (reslizumab), an asthma drug (See Table III at the end of article at end of article).

The three parenteral drugs by smaller companies approved in 2016 included: Elusys Therapeutics’ Anthim (obiltoxaximab) for treating inhalation anthrax; Jazz Pharmaceuticals’ Defitelio (defibrotide sodium) for treating hepatic veno-occlusive disease; and Sarepta Therapeutics’ Exondys 51 (eteplirsen) for treating Duchenne muscular dystrophy (See Table III at the end of article at end of article).

Parenteral drug approvals: 2015

For 2015, 12 parenteral drugs approved were from leading pharma companies. These included: Amgen’s Repatha (evolocumab), an anti-cholesterol drug; Astellas Pharma’s Cresemba (isavuconazonium sulfate), an anti-fungal for treating invasive aspergillosis and invasive mucormycosis (note: Cresamab was also approved in an oral dosage form); Boehringer Ingelheim’s Praxbind (idarucizumab), a blood coagulant for reversing the effects of blood-thinning medication; Bristol-Myers Squibb’s Empliciti (elotuzumab) for treating multiple myeloma; Eli Lilly and Company’s Portrazza (necitumumab), a lung-cancer drug; GlaxoSmithKline’s Nucala (mepolizumab), an asthma therapy; Janssen Biotech’s Darzalex (daratumumab) for treating multiple myeloma; Janssen Products’ Yondelis (trabectedin) for treating specific soft tissue sarcomas; Merck & Co.’s Bridion (sugammadex), an anti-neuromuscular-blocker drug; Novartis’ Cosentyx (secukinumab), a plaque psoriasis drug; Novo Nordisk’s Tresiba (insulin degludec injection), a diabetes treatment; and Sanofi’s and Regeneron Pharmaceuticals’ Praluent (alirocumab), an anti-cholesterol drug.

The remaining eight parenteral drug approvals in 2015 were from smaller companies. These included: Alexion Pharmaceuticals’ Kanuma (sebelipase alfa) for treating lysosomal acid lipase deficiency, and Strensiq (asfotase alfa) for treating hypophosphatasia; Alkermes’ Aristada (aripiprazole lauroxil), an anti-schizophrenia drug; Cerexa’s Avycaz (ceftazidime-avibactam), an anti-infective; Kythera Biopharmaceuticals’ Kybella (deoxycholic acid), for treating moderate-to-severe fat below the chin (note Kythera was acquired by Allergan in 2015); NPS Pharma’s Natpara (parathyroid horomone), a hypoparathyroidism therapy (note: NPS Pharma was acquired by Shire in 2015); The Medicines Company’s Kengreal (cangrelor), an anti-blood clotting drug; and United Therapeutics’ Unituxin (dinutuximab), for treating neuroblastoma.

Parenteral drug approvals: 2014

In 2014, nine parenteral drugs were approved from major pharma companies. These drugs included Amgen’s Blincyto (blinatumomab), a leukemia drug; Biogen’s (peginterferon beta-1a), a multiple sclerosis drug; Bristol-Myers Squibb’s Opdivo (nivolumab), an anti-cancer drug; GlaxoSmithKline’s Tanzeum (albiglutide), an anti-diabetes drug; Eli Lilly and Company’s Cyramza (ramucirumab), a stomach cancer drug and Trulicity (dulaglutide), an anti-diabetes drug; Janssen Biotech’s Sylvant (siltuximab) for treating multicentric Castleman’s disease; Merck & Co.’s Keytruda (pembrolizumab), an anti-cancer drug; and Takeda Pharmaceutical’s Entyvio (vedolizumab) for treating ulcerative colitis and Crohn’s disease.

Smaller companies accounted for the remaining seven parenteral drug approvals in 2014. These included: Amylin Pharmaceuticals’ Myalept (metreleptin for injection) for treating leptin deficiency; BioCryst Pharmaceuticals’ Rapivab (peramivir) for treating influenza; Biomarin Pharmaceuticals’ Vimizim (elosulfase alfa) for treating mucopolysaccharidosis; Cubist Pharmaceuticals’ Sivextro (tedizolid phosphate), an antibacterial drug (note: Merck & Co. acquired Cubist Pharmaceuticals in 2015); Durata Therapeutics’ Dalvance (dalbavancin), an antibacterial drug; The Medicines Company’s Orbactiv (oritavancin), an antibacterial drug; and Spectrum Pharmaceuticals’ Beleodaq (belinostat), an anti-cancer drug.

Impact on ingredient supply

Increased development of parenteral drugs impacts the supply of ingredients and related services. For example, the market for specialty excipients in the parenteral segment is expected to grow at 7.5% annually in the US and Europe combined in the next five years, according to a recent analysis, Specialty Excipients for Parenteral Pharmaceuticals: Market Analysis and Opportunities, by Kline and Company, a Parsippany, New Jersey business intelligence firm.

“There is no doubt that oral route continues to be the major market for excipients globally due to their high patient compliance and competitive manufacturing costs; however, injectable is a much faster growing segment," said Shilpi Mehrotra, the report's manager, in commenting on the report. "With the emergence of increasingly complex APIs, notably large biologics, and poorly soluble small molecules, the parenteral pharmaceuticals segment is creating new opportunities for excipients suppliers."

North America and Europe together make up more than 80% of the market of specialty parenteral excipients. Liquid solutions is the largest formulation market for parenteral excipients while market shares vary by volume and value due to their prices, according to the Kline study. Certain excipients have very high prices, which leads to a high value share despite low-volume consumption.

Dextrose is the most widely used specialty excipient in the parenteral formulations segment by both volume and value, according to the Kline study. The wide use of dextrose and sodium chloride is primarily because they are used as tonicity-adjusting agents crucial for parenteral formulations, which must be isotonic with blood, notes the study. Polysorbate-80 is expected to witness the highest growth as it is one of the most used surfactants in parenteral formulations in lyophilized, liquid solutions, and suspensions.

Table II: Parenteral Drugs Approved as New Molecular Entities--New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) in 2017 by the US Food and Drug Administration’s Center for Drug Evaluation and Research (as of October 31, 2017).
Company Brand name (active ingredient); application type Indication
Amgen Parsabiv (etelcalcetide); NDA Secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis
AstraZeneca Imfinzi (durvalumab); BLA Locally advanced or metastatic urothelial carcinoma (bladder cancer)
Bayer Aliqopa (copanlisib); NDA Relapsed follicular lymphoma
BioMarin Pharmaceutical Brineura (cerliponase alfa); BLA A specific form of Batten disease
Johnson & Johnson (Janssen Biotech) Tremfya (guselkumab); BLA Moderate-to-severe plaque psoriasis
Melinta Therapeutics Baxdela (delafloxacin); NDA Acute bacterial skin infections
Merck KGaA and Pfizer Bavencio (avelumab); BLA Metastatic Merkel cell carcinoma (a rare form of skin cancer)
Mitsubishi Tanabe Pharma America Radicava (edaravone); NDA Amyotrophic lateral sclerosis (Lou Gehrig’s disease)
Radius Health Tymlos (abaloparatide); NDA Osteoporosis
Roche Ocrevus (ocrelizumab); BLA Relapsing forms of multiple sclerosis and primary progressive multiple sclerosis
Sanofi and Regeneron Pharmaceuticals Dupixent (dupilumab); BLA Moderate-to-severe eczema (atopic dermatitis)
Sanofi Kevzara (sarilumab); BLA Rheumatoid arthritis
The Medicines Company Vabomere (meropenem and vaborbactam); NDA Complicated urinary tract infections
Valeant Pharmaceuticals Siliq (brodalumab); BLA Moderate-to-severe plaque psoriasis

Melinta Therapeutics’ Baxdela (delafloxacin) was also approved in an oral dosage form.

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

 

Table III: Parenteral Drugs Approved as New Molecular Entities--New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) in 2016 by the US Food and Drug Administration’s Center for Drug Evaluation and Research.
Company Brand name (active ingredient); application type Indication
Biogen Spinraza (nusinersen); NDA Spinal muscular atrophy
Biogen Zinbryta (daclizumab); BLA Multiple sclerosis
Eli Lilly and Company Lartruvo (olaratumab); BLA Certain types of soft tissue sarcoma
Eli Lilly and Compny Taltz (ixekizumab); BLA Moderate-to-severe plaque psoriasis
Elusys Therapeutics Anthim (obiltoxaximab); BLA Inhalational anthrax in combination with appropriate antibacterial drugs
Jazz Pharmaceuticals Defitelio (defibrotide sodium); NDA Hepatic veno-occlusive disease
Merck & Co. Zinplava (bezlotoxumab); BLA Clostridium difficile infection, for patients 18 years of age or older
Roche Tecentriq (atezolizumab); BLA Urothelial carcinoma (i.e., bladder cancer)
Sanofi Adlyxin (lixisenatide); NDA Type 2 diabetes, for improving blood sugar levels
Sarepta Therapeutics Exondys 51 (eteplirsen); NDA Duchenne muscular dystrophy
Teva Pharmaceutical Industries Cinqair (reslizumab); BLA Severe asthma

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 June 2016, and with it, Eucrisa (crisaborole).

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