Solid Dosage Versus Parenterals: Which Leads in New Drug Development?

Solid dosage products are a mainstay of new drug development, but parenteral drug development is on the rise. So which product form leads in new drug development? DCAT Value Chain Insights (VCI) examines key trends.

The rise in biologic-based drug development is a contributing factor to the increase in the number of parenteral drugs under development and recently approved new molecular entities (NMEs). With recent highs in the number of NMEs approved in the US in 2015 and 2014, what is the report card on solid dosage and parenteral drugs? DCAT Value Chain Insights (VCI) looks at the number of approvals and drugs approved.;

NME watch: solid dosage versus parenterals
Last year was a banner year for approval of NMEs with 45 NMEs approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research, a recent high. Table I outlines the 45 NMEs approvals in 2015. Of the 45 NMEs approved, 32 were small molecules (new drug applications (NDAs)), one is an insulin analogue approved as a NDA, and 12 are biologics (biologics license applications (BLAs) (see Table I).

The small-molecule approvals in 2015 were: Actelion Pharmaceuticals’ Uptravi (selexipag); Alkmeres’ Aristada (aripiprazole lauroxil); Allergan’s (formerly Actavis) Viberzi (eluxadoline), Avycaz (ceftazidime-avibactam), Kybella (deoxycholic acid), and Vraylar (cariprazine); Amgen’s Corlanor (ivabradine); Asklepion Pharmaceuticals/Retrophin’s Cholbam (cholic acid); Astellas Pharma’s Cresemba (isavuconazonium); AstraZeneca’s Tagrisso (osimertinib) and Zurampic (lesinurad); Bristol-Myers Squibb’s Daklinza (daclatasvir); Daiichi Sankyo’s Savaysa (edoxaban); Eisai’s Lenvima (lenvatinib); Gilead Sciences’ Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide); Johnson & Johnson’s Yondelis (trabectedin); Merck & Co. ‘s Bridion (sugammadex); Novartis’ Farydak (panobinostat), Odomzo (sonidegib), and Entresto (sacubitril/valsartan); Otsuka Pharmaceutical’s Rexulti (brexpiprazole); Pfizer’s Ibrance (palbociclib); Roche’s Cotellic (cobimetinib) and Alecensa (alectinib); Sprout Pharmaceuticals’ Addyi (flibanserin) (Valeant Pharmaceuticals is acquiring Sprout Pharmaceuticals); Taiho Oncology’s Lonsurf (trifluridine and tipiracil); Tesaro’s Varubi (rolapitant); Takeda Pharmaceuticals’ Ninlaro (ixazomib); The Medicines Company’s Kengreal (cangrelor); Vertex Pharmaceuticals’ Orkambi (lumacaftor and ivacaftor); and Wellstat Therapeutics’ Xuriden (uridine triacetate).

Of these small molecules, seven are parenteral drugs (see Table I).These are: Alkmeres’ Aristada (aripiprazole lauroxil); Allergan’s Avycaz (ceftazidime-avibactam); Allergan’s Kybella (deoxycholic acid); Astellas Pharma’s Cresemba (isavuconazonium) (also delivered in capsule form orally); Johnson & Johnson’s Yondelis (trabectedin); Merck & Co.’s Bridion (sugammadex); and The Medicines Company’s Kengreal (cangrelor);

Twelve biologics were approved in 2015, all delivered parenterally (see Table I). These were: Alexion Pharmaceuticals’ Strensiq (asfotase alfa) and Kanuma (sebelipase alfa); Amgen’s Repatha (evolocumab); Boehringer Ingelheim’s Praxbind (idarucizumab); Bristol-Myers Squibb’s Empliciti (elotuzumab); Eli Lilly’s Portrazza (necitumumab); GlaxoSmithKline’s Nucala (mepolizumab); Johnson & Johnson’s Darzalex (daratumumab); Novartis’ Cosentyx (secukinumab); Sanofi/Regeneron Pharmaceuticals’ Praluent (alirocumab); Shire/NPS Pharmaceuticals’ Natpara (parathyroid hormone); and United Therapeutics’ Unituxin (dinutuximab). 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 (it was approved as a NDA and not as a BLA). Also, Astellas Pharma’s Cresemba (isavuconazonium) was approved in two separate dosage forms: capsule form, delivered orally and powder, delivered IV (infusion).

On a comparative basis, 20 NMEs approved in 2015 were parenteral drugs (includes Astella’s Cresemba in parenteral form and Novo Nordisk’s Tresiba) compared with 26 NME solid dosage products (includes Astella’s Cresemba in solid dosage form), keeping solid dosage products as the leading product form with 56% of all NME approvals in 2015. This is up from 2014, when 46% of the NMEs approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research were solid dosage products, but down from 2013, when 63% of the NMEs approved were solid dosage products.

Table I: 2015 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
Actelion Pharmaceuticals Uptravi (selexipag); NDA Pulmonary arterial hypertension Tablet; oral
Alexion Pharmaceuticals Strensiq (asfotase alfa); BLA Perinatal, infantile, and juvenile-onset hypophosphatasia Solution; injection
Alexion Pharmaceuticals Kanuma (sebelipase alfa); BLA Lysosomal acid lipase deficiency Injectable; injection
Alkermes Aristada (aripiprazole lauroxil) extended-release injection; NDA Schizophrenia Suspension; extended-release intramuscular
Allergan Viberzi (eluxadoline); NDA Irritable bowel syndrome with diarrhea Tablet; oral
Allergan Avycaz (ceftazidime-avibactam); NDA Complicated intra-abdominal infections in combination with metronidazole, and complicated urinary tract infections, including kidney infections Powder: IV (infusion)
Allergan/Forest Laboratories Vraylar (cariprazine); NDA Schizophrenia and bipolar disorder in adults. Capusle; oral
Allergan/Kythera Biopharmaceuticals Kybella (deoxycholic acid); NDA Moderate-to-severe fat below the chin Solution; subcutaneous
Amgen Corlanor (ivabradine): NDA To reduce hospitalization from worsening heart failure Tablet; oral
Amgen Repatha (evolocumab); BLA For some patients who are unable to get their low-density lipoprotein (LDL) cholesterol under control with current treatment options Injectable; injection
Asklepion Pharmaceuticals/Retrophin Cholbam (cholic acid); NDA Pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects and for patients with peroxisomal disorders Capsule; oral
Astellas Pharma Cresemba (isavuconazonium; NDA Invasive aspergillosis and invasive mucormycosis Capsule; oral and also as Powder; IV (nfusion)
AstraZeneca Tagrisso (osimertinib); NDA Advanced non-small cell lung cancer in patients whose tumors have a specific epidermal growth factor receptor (EGFR) mutation (T790M) and whose disease has gotten worse after treatment with other EGFR-blocking therapy Tablet; oral
AstraZeneca Zurampic (lesinurad); NDA To treat high levels of uric acid in the blood (hyperuricemia) associated with gout Tablet; oral
Boehringer Ingelheim Praxbind (idarucizumab); BLA In patients who are taking the anticoagulant Pradaxa (dabigatran) during emergency situations when there is a need to reverse Pradaxa’s blood-thinning effects. Injectable; injection
Bristol-Myers Squibb Empliciti (elotuzumab); BLA In combination with two other therapies to treat people with multiple myeloma who have received one to three prior medications Injectable; injection
Bristol-Myers Squibb Daklinza (daclatasvir); NDA For use with sofosbuvir to treat hepatitis C virus genotype 3 infections Tablet; oral
Daiichi Sanyko Savaysa (edoxaban); NDA Reduce the risk of stroke and dangerous blood clots in patients with atrial fibrillation that is not caused by a heart valve problem. Tablet; oral
Eisai Lenvima (lenvatinib); NDA; orphan drug Progressive, differentiated thyroid cancer whose disease progressed despite receiving radioactive iodine therapy Capsule; oral
Eli Lilly and Company Portrazza (necitumumab); BLA In combination with two forms of chemotherapy to treat patients with advanced (metastatic) squamous non-small cell lung cancer who have not previously received medication specifically for treating their advanced lung cancer Injectable; intra-articular, intramuscular, intravitreal
GlaxoSmithKline Nucala (mepolizumab); BLA With other asthma medicines for the maintenance treatment of asthma in patients age 12 years and older Injectable: subcutaneous lyophilized powder
Gilead Sciences Genvoya (a fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide); NDA HIV-1 infection in adults and pediatric patients 12 years of age and older Tablet; oral
Johnson & Johnson (Janssen Biotech) Darzalex (daratumumab); BLA To treat patients with multiple myeloma who have received at least three prior treatments Injectable; injection
Johnson & Johnson (Janssen Products) Yondelis (trabectedin); NDA Specific soft tissue sarcomas, liposarcoma and leiomyosarcoma, that cannot be removed by surgery or is advanced Powder; IV (infusion)
Merck & Co. Bridion (sugammadex); NDA To reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide Solution; intravenous
Novartis Farydak (panobinostat); NDA; orphan drug Multiple myeloma Capsule; oral
Novartis Cosentyx (secukinumab); BLA Moderate-to-severe plaque psoriasis Injectable; injection
Novartis Odomzo (sonidegib); NDA Locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or for patients who are not candidates for surgery or radiation therapy Capsule; oral
Novartis Entresto (sacubitril/valsartan); NDA Chronic heart failure Tablet; oral
Novo Nordisk Tresiba (insulin degludec injection); NDA To improve blood sugar (glucose) control in adults with diabetes mellitus. Solution; subcutaneous
NPS Pharmaceuticals/Shire Natpara (parathyroid horomone); BLA Control hypocalcemia (low blood calcium levels) in patients with hypoparathyroidism Injectable; injection
Otsuka Pharmaceutical Rexulti (brexpiprazole); NDA Adults with schizophrenia and as an add-on treatment to an antidepressant medication to treat adults with major depressive disorder Tablet; oral
Pfizer Ibrance (palbociclib); NDA Metastatic breast cancer Capsule; oral
Relypsa Veltassa (patiromer sorbitex calcium); NDA Hyperkalemia (high potassium levels) Powder; oral
Roche/Genentech Cotellic (cobimetinib); NDA In combination with vemurafenib to treat advanced melanoma that has spread to other parts of the body or can’t be removed by surgery, and that has a certain type of abnormal gene (BRAF V600E or V600K mutation) Tablet; oral
Roche/Genentech Alecensa (alectinib); NDA Advanced ALK-positive non-small cell lung cancer Capsule; oral
Sanofi/Regeneron Pharmaceuticals Praluent (alirocumab); BLA For certain patients with high cholesterol Injectable; injection
Sprout Pharmaceuticals Addyi (flibanserin); NDA Acquired, generalized hypoactive sexual desire disorder in premenopausal women Tablet; oral
Taiho Oncology Lonsurf (trifluridine and tipiracil) NDA Advanced colorectal cancer Tablet; oral
Takeda Pharmaceuticals Ninlaro (ixazomib); NDA In combination with two other therapies to treat people with multiple myeloma who have received at least one prior therapy. Capsule; oral
Tesaro Varubi (rolapitant); NDA To prevent delayed phase chemotherapy-induced nausea and vomiting Tablet; oral
The Medicines Company Kengreal (cangrelor); NDA  Anticoagulant for adult patients undergoing percutaneous coronary intervention Powder; IV (infusion)
United Therapeutics Unituxin (dinutuximab); BLA; First-line therapy for pediatric patients with high-risk neuroblastoma Injectable; intravenous
Vertex Pharmaceuticals Orkambi (lumacaftor and ivacaftor); NDA Cystic fibrosis in patients who have two copies of a specific mutation Tablet; oral
Wellstat Therapeutics Xuriden (uridine triacetate); NDA Hereditary orotic aciduria, a rare metabolic disorder Granule; oral

Actavis changed its corporate name to Allergan in June 2015.
Allergan acquire Kythera Biopharmaceuticals in 2015.
Novo Nordisk’s Tresiba (insulin degludec injection) is a long-acting basal human insulin analog produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification. It was approved as a new drug application not as a biologics license application.
Retrophin agreed to acquire Chobalm from Asklepion Pharmaceuticals in January 2015 and exercised a purchase agreement in March 2015.
Shire acquired NPS Pharmaceuticals in February 2015.
Valeant Pharmaceuticals agreed to agree Sprout Pharmaceuticals in August 2015.
Source: US Food and Drug Administration’s Center for Drug Evaluation and Research and company information.


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