published 02/09/2010

The first replacement therapy for von Willebrand disease. The first medicine developed specifically for peripheral T-cell lymphoma. The first therapy for treating the acute abdominal and facial attacks of hereditary angioedema. The first recombinant biologic manufactured in goats. The first vaccine manufactured in insect cell cultures. Indeed: 2009 was a great year for new product approvals – but they weren’t all “firsts.” The agency also gave the nod to therapies for rheumatoid arthritis, plaque psoriasis, renal cell carcinoma, and pulmonary hypertension (among others). As well, the line that separates biotech and specialty pharma companies on the one hand from traditional big pharma outfits on the other has nearly disappeared as the latter implement strategic shifts towards biopharmaceuticals and niche markets.

Those who subscribe to the notion that there’s a mounting backlog of drug applications at the FDA – and that the agency is missing most of its PDUFA dates – will be surprised to learn that the data support neither premise. Au contraire: The FDA granted first-time approvals to more biotech and biotech-derived biologics and drugs in 2009 than it had since at least 2000. Last year, 16 new biologics and 32 new drugs (48 in all) received the agency’s blessing – and almost all of the final approvals came on or within a day or two of the PDUFA date (by which the FDA is required to review and act on submissions and resubmissions of NDAs and BLAs).

Importantly, the number of new biologics approved in 2009 (16) was substantially higher than the number for 2008 (11) or 2007 (9) – reversing an alarming downward trend. On the other hand, the number of new drugs approved in 2009 (32) was about on par with those approved in 2008 (31) and 2006 (31), although the number dropped to 27 in 2007. (For a list of new product approvals in 2008, click here.)

On first glance, then, 2009 looks like a great year for new product approvals. But when we dig a little deeper, we see that many of these therapies are not absolutely new – even though they were approved under NDAs or BLAs rather than supplemental applications. In the FDA’s parlance, new new drugs -- known as new molecular entities (NMEs) or new chemical entities (NCEs) – are unique compounds that have never been included in any other drug application. The same logic applies to biologics: We designate those that are truly unique as new biologic entities (NBEs).

Under these definitions, nine of the 32 drugs approved in 2009 under NDAs were NCEs (designated with two asterisks in the tables that follow). The rest were new indications, new formulations, or new esters, salts and the like of already-approved drugs. On the other hand, 13 of the 16 biologics approved under BLAs in 2009 were NBEs (designated with triple asterisks in the tables).

Biotech And Biotech-Related Products Approved By FDA In 2009*

Product Name	Company (s) (Developer; Marketer)	Product Description	Indication	Approval (Date)
Adcirca (tadalafil)	United Therapeutics; Eli Lilly	Once-daily phosphodiesterase type 5 (PDE5) inhibitor; oral	Pulmonary arterial hypertension to improve exercise ability	5/09
Afinitor** (everolimus)	Novartis	Inhibits mTOR, a serine threonine kinase	Treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib	3/09
Agriflu	Novartis	Inactivated influenza virus surface antigen vaccine (seasonal flu)	Active immunization of adults 18 years of age and older against influenza caused by virus subtypes A and B	11/09
Arzerra*** (ofatumumab; HuMax-CD20)	Genmab; GlaxoSmithKline	Fully human monoclonal antibody that targets the CD20 molecule on B cells	Treatment of chronic lymphocytic leukemia that is refractory to previous therapies fludarabine and Campath	10/09
ATryn***	GTC Biotherapeutics; Ovation Pharmaceuticals	Recombinant human anti-thrombin produced in transgenic goats	Prevention of deep vein thrombosis and other thromboembolisms in patients with hereditary antithrombin deficiency	2/09
Bepreve** (bepotastine ophthalmic solution)	ISTA Pharmaceuticals	Non-sedating, highly selective antagonist of the histamine (H1) receptor	Eye drop treatment for ocular itching associated with allergic conjunctivitis in patients 2 years of age and older	9/09
Berinert*** (C1-IHN)	CSL Behring	C1-esterase inhibitor (human plasma-derived)	Treatment of acute abdominal and facial attacks of hereditary angioedema in adults and adolescents	10/09
Besivance** (besifloxacin ophthalmic solution)	Bausch & Lomb; InSite Vision	Broad-spectrum anti-infective drug formulated with InSite Vision’s DuraSite technology (synthetic polymer delivery vehicle)	Bacterial conjunctivitis in patients 1 year of age and older	5/09

* Includes first-time approval in the U.S. for drugs, biologics and vaccines developed by biotechnology and specialty pharma companies as well as biotech-derived products developed by pharmaceutical companies. **New chemical entity. *** New biologic entity.

The biologics that were not NBEs include Extavia, Gammaplex and Agriflu. Novartis AG’s Extavia, a recombinant human interferon beta-1b, is the same medicinal product as Bayer Schering AG’s Betaseron. Novartis gained the rights to seek approval for its own branded version of the multiple sclerosis drug from Bayer in 2007. And Bio Products Laboratory’s Gammaplex, a human intravenous immune globulin (IVIG) approved for treating primary humoral immunodeficiency, is only one of a large number of IVIGs on the market and thus can’t be considered a unique product either.

Lastly, Novartis’ seasonal flu vaccine Agriflu is hardly unique – although it appears to be the only one approved under a full BLA in 2009. Last year’s other flu vaccines – both seasonal and those directed against the 2009 H1N1 virus -- were approved under supplemental BLAs since they use the same manufacturing processes as earlier versions of flu vaccines and have a long history of safety.

A number of the NBEs approved in 2009 address rare or orphan diseases, most of which are genetic. Octapharma USA’s Wilate, for instance, is the first and only replacement therapy developed specifically for von Willebrand disease (VWD), an hereditary bleeding disorder that results from the body’s inability to make the blood clotting protein von Willebrand factor.

The FDA approved two biological therapies for hereditary angioedema (HAE), a rare and serious genetic disorder that can cause considerable swelling in various body tissues. These attacks are unpredictable and usually occur spontaneously. In October, Berinert, a C1-esterase inhibitor (C1-INH) developed by CSL Behring, became the first and only replacement therapy for treating the acute abdominal and facial attacks associated with HAE. In December, the agency approved Kalbitor, Dyax Corp.’s plasma kallikrein inhibitor, as a subcutaneous treatment for acute attacks of HAE regardless of their location in the body.

Biotech And Biotech-Related Products Approved By FDA In 2009*

Product Name	Company (s) (Developer; Marketer)	Product Description	Indication	Approval (Date)
Byetta (exenatide)	Amylin Pharmaceuticals; Eli Lilly and Co.	GLP-1 receptor agonist	For use as an adjunct to diet and exercise to improve glycemic control in adults with Type II diabetes	10/09
Caldolor (formerly Amelior)	Cumberland Pharmaceuticals	IV formulation of ibuprofen	Treatment of pain and fever, primarily in hospitalized patients who are unable to receive oral therapy	6/09
Cervarix*** (human papillomavirus vaccine; AS04 adjuvant-adsorbed)	GlaxoSmithKline	Vaccine for cervical cancer; human papillomavirus (HPV) bivalent (types 16 and 18) vaccine, recombinant	Prevention of cervical cancer and precancerous lesions associated with oncogenic HPV types 16 and 18 for use in girls and young women (aged 10-25 years)	10/09
Creon (pancrelipase)	Solvay Pharmaceuticals	Pancreatic enzyme; contains a mixture of digestive enzymes from pig pancreas (delayed-release capsules)	Treatment of exocrine pancreatic enzyme insufficiency due to cystic fibrosis or other conditions	4/09
Dysport*** (formerly Reloxin; abobotulinumtoxinA)	Medicis; Ipsen	Botulinum toxin type A, an acetylcholine release inhibitor and a neuromuscular blocking agent	Treatment of cervical dystonia in adults. Also for the temporary improvement in the appearance of wrinkles in adults younger than 65.	4/09
Edluar (formerly Sublinox; zolpidem tartrate)	Orexo Pharma; Meda	Non-benzodiazepine sedative hypnotic (sublingual tablets)	Short-term treatment of insomnia characterized by difficulties with sleep initiation	3/09
Extavia (Interferon beta-1b)	Novartis	Recombinant human interferon	Relapsing forms of multiple sclerosis; also indicated for patients who have experienced a first clinical episode of MS	8/09
Fanapt** (iloperidone)	Vanda Pharmaceuticals; Novartis	Atypical antipsychotic; a mixed dopamine D2/serotonin 5HT2A receptor antagonist	Acute treatment of adults with schizophrenia	5/09

* Includes first-time approval in the U.S. for drugs, biologics and vaccines developed by biotechnology and specialty pharma companies as well as biotech-derived products developed by pharmaceutical companies. **New chemical entity. *** New biologic entity.

Then there’s Ilaris, which is approved for treating children and adults with cryoporin-associated periodic syndromes (CAPS), a number of rare and serious auto-inflammatory diseases caused by a genetic mutation that leads to overproduction of interleukin-1 (IL-1) beta. Developed by Novartis, Ilaris is a fully human monoclonal antibody that rapidly and selectively blocks IL-1 beta.

CSL Behring garnered FDA approval for a second rare-disease therapy in January 2009. This product, RiaSTAP, is a fibrinogen concentrate made from human plasma that became the first and only approved treatment for acute bleeding episodes in patients with congenital fibrinogen deficiency, a potentially life-threatening bleeding disorder.

Moreover, the agency also approved a new therapy for the rare clotting disorder hereditary antithrombin deficiency, which puts afflicted individuals at high risk of developing blood clots during surgery and childbirth. Developed by GTC Biotherapeutics Inc., ATryn is designed to prevent blood clots in these individuals. It also claims a number of “firsts:” ATryn is the first FDA-approved recombinant protein-based therapy manufactured in goats as well as the first associated with a New Animal Drug Application, which regulates genetically engineered animals.

And, for the first time, there’s a medicine specifically for peripheral T-cell lymphoma (PTCL), an often aggressive type of non-Hodgkin’s lymphoma and another rare disease. The drug Folotyn, developed by Allos Therapeutics Inc. and its first approved product, is a targeted anti-folate compound designed to accumulate preferentially in cancer cells. It garnered accelerated approval in September, and is indicated for treating patients with relapsed or refractory PTCL.

Biotech And Biotech-Related Products Approved By FDA In 2009*

Product Name	Company (s) (Developer; Marketer)	Product Description	Indication	Approval (Date)
Feraheme (ferumoxytol)	AMAG Pharmaceuticals	Superparamagnetic iron oxide particles with a semi-synthetic carbohydrate coating	Treatment of iron deficiency anemia in adult patients with chronic kidney disease	6/09
Folotyn (pralatrexate)	Allos Therapeutics	Targeted antifolate designed to accumulate preferentially in cancer cells	Treatment of patients with relapsed or refractory peripheral T-cell lymphoma	9/09
Gammaplex	Bio Products Laboratory	Immune globulin IgG (human)	Treatment of patients with primary humoral immunodeficiency	9/09
Hiberix*** (Haemophilus b Conjugate Vaccine [Tetanus Toxoid Conjugate])	GlaxoSmithKline	Vaccine against Haemophilus influenza type b (Hib), which can cause meningitis	For use as a booster dose in children 15 months through 4 years of age to prevent invasive disease caused by H. influenzae type b	8/09
Ilaris*** (formerly ACZ885, canakinumab)	Novartis	Fully human monoclonal antibody that rapidly and selectively blocks IL-1 beta	Treatment of children and adults with cryopyrin-associated periodic syndromes (CAPS), a number of rare, serious life-long auto-inflammatory disorders caused by a single gene mutation that leads to overproduction of interleukin-1 beta	6/09
Istodax** (romidepsin)	Gloucester Pharmaceuticals; Fujisawa Pharmaceutical	Histone deacetylase inhibitor (small molecule drug)	Treatment of cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy	11/09
Ixiaro***	Intercell; Novartis	Purified inactivated virus vaccine for active immunization against  viral infections of Japanese encephalitis	Prevention of disease caused by Japanese encephalitis virus in individuals 17 years of age and older	3/09
Kalbitor*** (DX-88; ecallantide)	Dyax; Research Corporation Technologies	Small recombinant protein; inhibits plasma kallikrein	Acute attacks of hereditary angioedema in patients 16 years of age and older	11/09

* Includes first-time approval in the U.S. for drugs, biologics and vaccines developed by biotechnology and specialty pharma companies as well as biotech-derived products developed by pharmaceutical companies. **New chemical entity. *** New biologic entity.

Indeed, 2009 was a year of firsts. The first therapy manufactured in insect cell cultures (rather than cultures of bacterial or yeast cells) garnered the FDA’s approval in October. This product, GlaxoSmithKline plc’s cervical cancer vaccine Cervarix, can be prescribed to girls and young women 10-25 years of age for preventing cervical cancer and precancerous lesions associated with human papillomavirus (HPV) types 16 and 18. However, Cervarix isn’t the first cervical cancer vaccine on the market. That honor belongs to Merck & Co. Inc.’s HPV vaccine Gardasil, which garnered its first approval in June 2006.

The agency also approved several already-marketed products that heretofore weren’t required to undergo formal regulatory approval. The first of these was Creon, Solvay Pharmaceuticals Inc.’s pancrelipase for treating exocrine pancreatic enzyme insufficiency due to cystic fibrosis or other conditions.

The second was Zenpep, a pancrelipase developed by Eurand N.V. and approved for the same indication as Creon. Under the FDA’s new regulations, by April 2010 all pancreatic enzymes must have approved NDAs (even though they are biologics) and they must be manufactured under new guidelines. In fact, Zenpep was developed specifically to meet the new guidelines, whereas Solvay had been marketing Creon well before the current regulations came about.

Although a different sort of drug, the active ingredient in NeurogesX Inc.’s Qutenza patch for treating postherpetic neuralgia also has a long history of non-regulated use. Qutenza consists of capsaicin, the substance found in chili peppers.

Like many newly approved pharmaceuticals, Creon and Zenpep come with a Risk Evaluation and Mitigation Strategy (REMS), which is intended to ensure that the drug’s benefits outweigh its risks. The FDA now requires drug sponsors to develop REMs for drugs (and biologics) they deem risky before those products are approved for marketing. The REMS includes medication guides, patient package inserts, a communication plan for healthcare providers, and various requirements to ensure safe use.

The agency has been authorized to require REMS since 2007, but as the years go by it seems that more and more therapies fall into this category. Critics claim that the FDA is overstepping its boundaries, treading on territory that used to belong to pharmaceutical companies themselves and, in many cases, to prescribing physicians. Proponents see the policy as a logical extension of the agency’s mandate, which is to "promote and protect the public health by helping safe and effective products reach the market in a timely way, and monitoring products for continued safety after they are in use."

Biotech And Biotech-Related Products Approved By FDA In 2009*

Product Name	Company (s) (Developer; Marketer)	Product Description	Indication	Approval (Date)
Lamictal ODT	Eurand; GSK	Orally disintegrating tablet formulation of lamotrigine (uses Eurand’s Microcaps taste-masking and AdvaTab technologies)	Long-term treatment of Bipolar I Disorder in patients 18 years or older who have been treated for mood episodes with other medicine	5/09
Lysteda (formerly XP12B)	Xanodyne Pharmaceuticals	Tranexamic acid, an oral therapy that acts as a competitive plasmin inhibitor to prevent fibrinolysis	Treatment of heavy menstrual bleeding	11/09
Metozolv ODT (metoclopramide)	Salix Pharmaceuticals	Dopamine receptor antagonist; orally disintegrating tablets	Acute and recurrent diabetic gastroparesis and for symptomatic gastroesophageal reflux disease	9/09
Nexterone (amiodarone HCl)	Prism Pharmaceuticals; CyDex Pharmaceuticals	Cosolvent-free formulation of the antiarrhythmic agent Amiodarone IV	Treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia	1/09
Omeprazole	Santarus	Immediate-release tablet formulation of omeprazole, a proton pump inhibitor, combined with dual buffers	Treatment of heartburn and other symptoms associated with gastroesophageal reflux disease	12/09
Onsolis (formerly BEMA Fentanyl; fentanyl buccal soluble film)	BioDelivery Sciences International; Meda	Dissolvable polymer delivery system, formulated with fentanyl (an opioid narcotic), for application to the buccal membranes	Management of breakthrough pain in patients with cancer, 18 years of age and older, who are already receiving and who are tolerant to opioid therapy	7/09
Pennsaid (diclofenac sodium)	Nuvo Research; Covidien	Topical non-steroidal anti-inflammatory drug; uses Nuvo’s skin-penetrating technologies for topical delivery	Osteoarthritis of the knee	11/09
Qutenza (NGX-4010)	NeurogesX	High-concentration synthetic capsaicin in a dermal patch	Management of neuropathic pain due to post-herpetic neuralgia	11/09

* Includes first-time approval in the U.S. for drugs, biologics and vaccines developed by biotechnology and specialty pharma companies as well as biotech-derived products developed by pharmaceutical companies. **New chemical entity. *** New biologic entity.

Despite the long list of newly approved therapies for rare or orphan diseases, the FDA also gave the nod to a number of medicines for common, widespread diseases. These included two new products from Johnson & Johnson subsidiary Centocor Ortho Biotech: Simponi, a next-generation human TNF-alpha monoclonal antibody for treating rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis; and Stelara, a human monoclonal antibody that binds to interleukins 12 and 23 and can be prescribed for moderate-to-severe plaque psoriasis.

Another antibody-based therapy that gained approval last year was Arzerra, Genmab A/S’ fully human anti-CD20 monoclonal antibody and the company’s first approved drug. Developed in collaboration with GlaxoSmithKline, Arzerra was granted accelerated approval for treating chronic lymphocytic leukemia that is refractory to previous therapies fludarabine and Campath.

The FDA also approved three more drugs for kidney cancer in 2009. In March, Novartis’ Afinitor, a small molecule that targets mTOR kinase, won the agency’s blessing as a treatment for patients with advanced renal cell carcinoma (RCC) after failure of treatment with Sutent or Nexavar. In August, Roche’s anti-VEGF monoclonal antibody Avastin was approved as a combination therapy with interferon alpha-2a for metastatic RCC (its fifth disease indication). And in October GlaxoSmithKline’s Votrient, a tyrosine kinase inhibitor that targets VEGFR, PDGFR and c-Kit, became the sixth drug approved for treating kidney cancer since 2005.

As well, the agency approved Istodax, a histone deacetylase inhibitor for treating cutaneous T-cell lymphoma (CTCL) that was developed by Gloucester Pharmaceuticals Inc. The approval was a pivotal event for the company: Not only was Istodax the firm’s first drug to pass muster with the FDA but also it grabbed the attention of Celgene Corp., which decided to acquire Gloucester a month later for $340 million in cash and up to $300 million in milestones. Istodax was a perfect addition to Celgene’s portfolio of therapies for blood cancers, especially because the drug has also received orphan drug designation for CTCL and peripheral T-cell lymphoma (PTCL) as well as Fast Track status in PTCL.

Other approvals (not shown in the tables) in 2009 included two collagen-based products: Collagen Matrix Inc.’s collagen dental membrane, which consists of highly purified types I and III collagen derived from bovine dermis, was approved in October for use in oral surgeries involving guided tissue and bone regeneration. A month later, the FDA approved Kensey Nash Corp.’s Medeor Matrix, a porcine-based dermal extracellular matrix designed to act as a biological scaffold, for use in general surgery for the reinforcement and repair of soft tissue.

As well, Genzyme Corp.’s Synvisc-One garnered the FDA’s approval in February 2009. This product, which is an elastoviscous biopolymer derived from hyaluronic acid, is a new formulation of the firm’s original viscosupplement Synvisc, which has been on the market for 16 years as a treatment to relieve the pain associated with osteoarthritis of the knee. The difference? Patients need only inject Synvisc-One once every six months, while Synvisc requires three injections.

Biotech And Biotech-Related Products Approved By FDA In 2009*

Product Name	Company (s) (Developer; Marketer)	Product Description	Indication	Approval (Date)
Renvela (sevelamer carbonate)	Genzyme	Second-generation buffered form of Renagel; non-calcium, non-metal non-absorbed phosphate binder; powder packets	Control of serum phosphorus in patients with chronic kidney disease on dialysis	8/09
RiaSTAP***	CSL Behring	Fibrinogen (Factor I) concentrate made from pooled human plasma	Acute bleeding episodes in patients with congenital fibrinogen deficiency	1/09
Sabril** (vigabatrin)	Lundbeck (Ovation Pharmaceuticals)	Irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T); tablets and oral solution	Monotherapy for pediatric patients 1 month to 2 years of age with infantile spasms; also for use as an adjunctive therapy for adult patients with refractory complex partial seizures who have inadequately responded to alternative treatments; in both patient populations, for use when potential benefits outweigh the potential risk of vision loss	8/09
Savella** (milnacipran)	Cypress Bioscience; Laboratoires Pierre Fabre; Forest Laboratories	Dual-reuptake inhibitor (preferentially blocks the reuptake of norepinephrine with higher potency than serotonin)	Treatment of fibromyalgia syndrome	1/09
Simponi*** (Golimumab; CNTO 148)	Johnson & Johnson (Centocor); Schering-Plough; Mitsubishi Tanabe	Next-generation human anti-TNF-alpha monoclonal antibody; targets and neutralizes both the soluble and membrane-bound forms of TNF-alpha; delivered as a monthly subcutaneous injection	Treatment of rheumatoid arthritis (in combination with methotrexate), psoriatic arthritis (alone or in combination with methotrexate), and ankylosing spondylitis in adults	4/09
Stelara*** (ustekinumab; CNTO 1275)	Johnson & Johnson (Centocor Ortho Biotech); Medarex	Human Mab that binds to IL-12 and IL-23	Moderate-to-severe plaque psoriasis	9/09
Sumavel DosePro (sumatriptan)	Zogenix	Needle-free delivery system for subcutaneous sumatriptan (drug/device combo)	Treatment of acute migraine, with or without aura, and cluster headache	7/09
Tyvaso (treprostinil)	United Therapeutics (Lung Rx)	Inhaled formulation of approved drug Remodulin	Pulmonary arterial hypertension	7/09

* Includes first-time approval in the U.S. for drugs, biologics and vaccines developed by biotechnology and specialty pharma companies as well as biotech-derived products developed by pharmaceutical companies. **New chemical entity. *** New biologic entity.

Developing an approved therapy for additional indications is a tried and true way for companies to bolster sales and grow product franchises. And there was ample proof of this strategy in 2009 – during which the FDA approved 18 supplemental BLAs and 12 supplemental NDAs.

The biologics that garnered supplemental approvals in 2009 include (but are not limited to):

• Avastin: Genentech Inc., a wholly owned member of the Roche Group, won two more approvals for its anti-VEGF cancer therapy in 2009. In April, Avastin was approved for treating glioblastoma patients with progressive disease following prior therapy. In August, as we mentioned earlier, it was approved as a combination therapy with interferon alpha-2a for treating metastatic renal cell carcinoma. First approved in February 2004 for treating metastatic colorectal cancer, Avastin is now cleared for use in five different types of cancer.
• Cimzia: Developed by Celltech Group plc (which was acquired by UCB S.A. in August 2004), Cimzia was approved in May for treating active rheumatoid arthritis in adults. The product, a PEGylated fragment of an anti-TNF alpha antibody, won its first approval in April 2008 for treating moderate-to-severe active Crohn’s disease.
• Gardasil: The FDA approved Merck & Co.’s human papillomavirus (HPV) vaccine Gardasil for preventing genital warts caused by HPV types 6 and 11 in boys and young men (ages 9 to 26) in October. The vaccine was first approved in June 2006 for preventing cervical cancer, pre-cancerous and low-grade lesions and genital warts caused by HPV types 6,11,16 and 18 in girls and young women (ages 9 to 26). It is also approved for preventing vulvar and vaginal cancers in girls and young women.
• Zevalin: In September, the FDA approved an expanded label for Spectrum Pharmaceuticals Inc.’s CD20-directed radiotherapeutic antibody Zevalin. First approved in February 2002 for treating low grade or follicular, relapsed or refractory, CD20-positive, B-cell non-Hodgkin's lymphoma and rituximab-refractory follicular NHL, Zevalin can now be used as a first-line therapy in patients with follicular non-Hodgkin’s lymphoma.

The FDA is off to a good start in 2010 – and there are plenty of new, still-experimental therapies waiting for their day in the sun this year.