US FDA approves 24 NMEs/novel biologicals in 2008

The USFDA's drugs centre (CDER) approved 21 new molecular entities and three novel biologicals in 2008, a 33% increase over its prior-year total of 18 and the highest level of novel medicine approvals since 2004. The centre also surpassed its 2007 totals for all original NDA and BLA approvals, with approximately 93 in 2008, up from 78 in the prior year.

(Editor's Note: this is an updated analysis of US NME and novel biological approvals for the full year. An article analysing the 12-month period of November 2007-October 2008 appears in the Scrip 100 special issue).

The increase in novel medicine approvals came despite missed user fee deadlines and other delays resulting from new requirements under the FDA Amendments Act. The FDA also continues to hear complaints that it has become too conservative in its approval decisions, an assertion that high-level CDER officials vigorously dispute. Nevertheless, the agency declined to approve such drugs as Schering-Plough's anaesthesia reversal agent Bridion (sugammadex) and Merck & Co's cholesterol-lowering medicine Cordaptive (niacin extended-release plus laropiprant).

NME breakdown

Four of the 21 NMEs were diagnostic imaging agents, accounting for the largest category of approvals. Three NMEs were for oncology indications:Cephalon's Treanda (bendamustine) for chronic lymphocytic leukaemia;Ferring Pharmaceuticals' degarelix for prostate cancer; andGenzyme's Mozobil (plerixafor), a haematopoietic stem cell mobiliser.

2008 saw the approval of two platelet boosters for patients with chronic immune (idiopathic) thrombocytopenic purpura –Amgen's injectable biological Nplate (romiplostim) was licensed in August, followed three months later by GlaxoSmithKline's Promacta (eltrombopag), an oral agent. The FDA approved two epilepsy medicines –Eisai's Banzel (rufinamide) and UCB's Vimpat (lacosamide) – with suicidality label warnings and medication guides even before the agency finalised plans for a similar class warning on all anti-epileptic products. Only one HIV medicine,Johnson & Johnson's Intelence (etravirine), made the cut last year.

FDAAA's provisions on risk evaluation and mitigation strategies (REMS) and mandatory postmarketing study requirements under Section 505(o) of the FD&C Act took effect on March 25th. The agency struggled throughout the year to interpret and apply the new safety authorities to pending applications. Several novel products that were ultimately approved, including Nplate, Promacta and Adolor/GSK's bowel function recovery drug Entereg (alvimopan), saw their user fee dates pass while the agency and sponsors navigated their way through the new regulatory scheme.

Among the 20 NMEs and new biologicals approved by the drugs centre after March 25th, eight had REMS and 13 had mandatory study requirements under Section 505(o) (see Table 1).

Table 1: 2008 US NME and new biological approvals by CDER

Product	Substance	Indication	Company	Date	REMS	Sec 505(o) studies
AdreView	lobenguane l 123	imaging agent	GE Healthcare	19/9/08	No	No
Arcalyst	rilonacept	cryopyrin-associated periodic syndromes	Regeneron	27/2/08	No*	No*
Banzel	rufinamide	Lennox-Gastaut syndrome seizures	Eisai	14/11/08	Yes	Yes
Cimzia	certolizumab pegol	Crohn's disease	UCB	22/4/08	Yes	Yes
Cleviprex	clevidipine	hypertension	The Medicines Company	1/8/08	No	No
N/A^†	degarelix	prostate cancer	Ferring Pharmaceuticals	24/12/08	No	Yes
Durezol	difluprednate	ocular surgery inflammation and pain	Sirion Therapeutics	23/6/08	No	No
Entereg	alvimopan	GI recovery following bowel surgery	Adolor/GlaxoSmithKline	20/5/08	Yes	Yes
Eovist	gadoxetate disodium	imaging agent	Bayer Healthcare	3/7/08	No	Yes
Intelence	etravirine	HIV	Tibotec (Johnson & Johnson)	18/1/08	No*	No*
Lexiscan	regadenoson	imaging agent	CV Therapeutics(licensed toAstellas)	10/4/08	No	Yes
Lusedra	fospropofol	monitored anaesthesia care sedation	Eisai	12/12/08	No	Yes
Mozobil	plerixafor	haematopoietic stem cell mobiliser	Genzyme	15/12/08	No	Yes
Nplate	romiplostim	thrombocytopenia	Amgen	22/8/08	Yes	Yes
Pristiq	desvenlafaxine	major depressive disorder	Wyeth	29/2/08	No*	No*
Promacta	eltrombopag	thrombocytopenia	GlaxoSmithKline	20/11/08	Yes	Yes
Rapaflo	silodosin	benign prostatic hyperplasia	Watson Pharmaceuticals(licensed fromKissei Pharmaceutical)	8/10/08	No	No
Relistor	methylnaltrexone	opioid-induced constipation	Progenics/Wyeth	24/4/08	No	No
N/A^†	tapentadol	moderate to severe acute pain	Johnson & Johnson	20/11/08	Yes	No
Toviaz	fesoterodine	overactive bladder	Pfizer(licensed from Schwarz Pharma/UCB)	31/10/08	No	No
Treanda	bendamustine	chronic lymphocytic leukaemia	Cephalon (licensed from Astellas)	20/3/08	No*	No*
Vasovist	gadofosveset	imaging agent	Epix Pharmaceuticals (licensed to Bayer Schering Pharma until March)	22/12/08	No	Yes
Vimpat	lacosamide	epileptic seizures	Schwarz Biosciences (UCB)	28/10/08	Yes	Yes
Xenazine	tetrabenazine	Huntington's disease chorea	Prestwick Pharmaceuticals (Biovail)	15/8/08	Yes	Yes
*approved prior to March 25th effective date of FDAAA drug safety provisions; ^†trade name not available

The agency's biologicals centre (CBER) approved four novel therapeutic products, the same number as last year, including Lev Pharmaceuticals' (nowViroPharma) Cinryze (C1 esterase inhibitor (human)) for prevention of attacks in patients with hereditary angioedema (see Table 2). CBER licensed three new vaccines in 2008, equalling its 2007 output (see Table 3).

Table 2: 2008 US new therapeutic biological approvals by CBER

Product	Substance	Indication	Company	Date	REMS	Sec 505(o) studies
Artiss	fibrin sealant (human)	skin graft attachment in burn patients	Baxter Healthcare	19/3/08	No*	No*
Cinryze	C1 esterase inhibitor (human)	hereditary angioedema	Lev Pharmaceuticals (ViroPharma)	10/10/08	No	Yes
Recothrom	thrombin topical (recombinant)	aid to haemostasis	Zymogenetics	17/1/08	No*	No*
Xyntha	antihaemophilic factor (recombinant) plasma/albumin free	haemophilia A	Wyeth Pharmaceuticals	21/2/08	No*	No*
* approved prior to March 25th effective date of FDAAA drug safety provisions

Table 3: 2008 US vaccine approvals

Product	Indication	Company	Date	REMS	Sec 505(o) studies
Kinrix	diphtheria/tetanus/pertussis/polio	GlaxoSmithKline	24/6/08	No	No
Pentacel	diphtheria/tetanus/pertussis/polio/Haemophilus influenzae type B	Sanofi Pasteur	20/6/08	No	No
Rotarix	rotavirus	GlaxoSmithKline	3/4/08	No	Yes