The FDA approved 25 new biotech and biotech-derived medicines in 2003 – far above the 15 new therapies approved in 2002 and arguably biotech’s best year yet. It’s an impressive array of products, too – many of which are first-in-kind therapies that address unmet medical needs. Interestingly, biotech companies have come up with more small molecule drugs than biologics – a phenomenon we’ve seen for a number of years. In 1996, for instance, about half of the sector’s new therapeutics were drugs; in 2003, that number increased to 68 percent. It’s a trend that’s likely to continue, too – even though biologics will always play an exceedingly important role in the therapeutics arena.
All you have to do is pay attention to TV commercials to realize the impact that biotechnology has had on people’s lives. Ads for the red blood cell boosters Epogen and Procrit have become commonplace. The arthritis drugs Enbrel and Remicade are routinely touted over the airwaves. And the commercials for the newly approved erectile dysfunction (ED) drug Cialis – nicknamed “the weekend pill” – are hard to miss these days.
The first four products have all achieved blockbuster status, too: Epogen and Procrit have reaped multi-billion dollar sales for years, and Enbrel and Remicade have broken through the billion-dollar level. Cialis, which was approved by the FDA in November 2003, may reach those lofty heights, too: 2003 sales of Viagra, the first ED drug to reach the market, were nearly $1.9 billion.
But Cialis, developed by Lilly ICOS LLC, is only one of the many important therapies approved by the FDA in 2003. The agency also gave its blessing to three new AIDS drugs – Gilead Sciences Inc.’s Emtriva, a once-daily medication that should greatly reduce the burden of treatment for patients; Trimeris Inc.’s Fuzeon, the first drug to block HIV’s entry into immune cells; and Vertex Pharmaceuticals Inc.’s Lexiva, which offers patients a flexible dosing regimen.
Psoriasis patients got a real lift, too: Last year, the FDA approved not one, but two new medicines for treating this oft-debilitating immune disorder: Biogen Idec Inc.’s Amevive and Raptiva, which was developed by Xoma Ltd. and Genentech Inc. Very importantly, these are the first two biological therapies to address the underlying cause of psoriasis.
As well, there are two new cancer therapies now available that attack malignancy at the molecular level: Millennium Pharmaceuticals Inc.’s Velcade is a small molecule that inhibits the proteasome, a housekeeping enzyme complex present in all cells that plays an important role in numerous biological pathways, including the growth of cancer cells. And AstraZeneca plc’s Iressa inhibits the epidermal growth factor receptor (EGFR), thus blocking the signaling pathways that play a major role in solid tumor growth. Both drugs are first-in-class, too – and their approvals add to the still-short list of targeted cancer therapies (which includes Novartis AG’s rationally designed signal transduction inhibitor Gleevec).
All told, 2003 was a very good year for biotech products – whether they were sponsored by biotech firms per se or by pharmaceutical companies. The FDA granted first-time approvals to 25 biotech and biotech-related therapies last year. (See the tables for details).
That’s an improvement over 2002 – when the FDA granted its blessing to 15 new therapies – and 2001 – when 12 new therapies were approved. It’s also a better track record than 2000 – which saw the introduction of 16 new biotech and biotech-related medicines.
Moreover, the average time it took for the FDA to approve these products – from the time the BLA or NDA was filed to marketing approval – improved in 2003 as compared to the previous year. In 2002, the average approval time for all new therapies was 27.3 months; in 2003, the average approval time was 19.9 months. The drugs, however, were approved more rapidly than the biologics. (For more details concerning the approval times for drugs and biologics in recent years, and a comparison to approval times in 1996 -- which was a high point in the agency's product-approval history -- see the Signals article, “FDA’s New Initiatives Taking Off.”)
Of the 25 new therapies approved in 2003, 68 percent are drugs, while only 32 percent are biologics. That’s not surprising, for few biotech firms these days constrain their drug development programs to recombinant proteins or monoclonal antibodies alone. Small molecule drug development plays a major role in most companies’ efforts to create new products. Others focus on applying creative technologies to deliver already approved drugs – from chemotherapeutics to antibiotics – as a relatively rapid way to approval. And, more often than not, drugs are the choice for the many firms that have taken to in-licensing clinical-stage products as a means to cut product development time and bolster their pipelines.
Biotech And Biotech-Related Drugs Approved In 2003*: First-Time Approvals
|
Product Name
|
Company (s) (Developer; Marketer)
|
Product Description
|
Indication
|
Approval Date
|
|
Aloxi
(palonosetron HCl)
|
MGI Pharma; Helsinn Healthcare
|
5-HT3 receptor antagonist
|
Prevention of acute and delayed nausea and vomiting caused by emetogenic
cancer chemotherapy
|
7/03
|
|
Cialis
(tadalafil)
|
Lilly ICOS LLC (Icos; Lilly JV)
|
PDE5 (phosphodiesterase) inhibitor
|
To improve erectile function up to 36 hours after dosing
|
11/03
|
|
Cubicin
(formerly Cidecin; daptomycin for injection)
|
Cubist Pharmaceuticals (Lilly); Chiron
|
Antibiotic (acidic lipopeptide)
|
Complicated skin and skin structure infections caused by Gram-positive
organisms (including S. aureus)
|
9/03
|
|
Emtriva
(formerly Coviracil; emtricitabine)
|
Gilead Sciences (Triangle Pharmaceuticals)
|
Nucleoside reverse transcriptase inhibitor
|
HIV infection (used in combination with other antiretroviral drugs;
one capsule, once-daily medication)
|
7/03
|
|
Estrasorb
(17-beta-estradiol)
|
Novavax, King Pharmaceuticals
|
Uses micellar nanoparticles to deliver natural hormone 17-beta-estradiol
through the skin (cream)
|
Topical estrogen replacement therapy for short-term use in reducing
vasomotor symptoms (hot flashes) in menopausal women
|
10/03
|
|
Factive
(gemifloxacin mesylate)
|
GeneSoft Pharmaceuticals; LG Life Sciences
|
Fluoroquinolone antibiotic
|
Mild-to-moderate community-acquired pneumonia and acute bacterial exacerbation
of chronic bronchitis
|
4/03
|
|
Fuzeon
(enfuvirtide; formerly T-20)
|
Trimeris; Hoffmann-La Roche
|
HIV fusion inhibitor; blocks virus from entering cells; 36-amino acid
peptide (binds to HIV surface protein gp41)
|
HIV-1 infection in patients with drug-resistant HIV (combination therapy
with other antiretroviral agents) (subcutaneous injection, twice daily)
|
3/03
|
|
Iressa
(gefitinib)
|
AstraZeneca Pharmaceuticals
|
Epidermal growth factor receptor-tyrosine kinase inhibitor (blocks
signaling pathways that play major role in solid-tumor growth)
|
Advanced non-small cell lung cancer in patients who have failed at
least two chemotherapy agents (3rd-line therapy) (once-daily oral tablet)
|
5/03
|
|
Lexiva
(fosamprenavir calcium; formerly
GW433908, 908 and VX-175)
|
Vertex Pharmaceuticals; GlaxoSmithKline
|
HIV protease inhibitor (prodrug of amprenavir [Agenerase])
|
HIV infection (once-daily and twice-daily dosing, with or without food
or water restrictions); used in combination with other antiretroviral
drugs
|
10/03
|
|
Namenda
(memantine HCl)
|
Neurobiological Technologies; Forest Laboratories; Merz + Co.
|
Small molecule NMDA receptor antagonist that blocks the abnormal effects
of glutamate
|
Moderate-to-severe Alzheimer’s disease
|
10/03
|
|
Plenaxis
(formerly Abarelix Depot)
|
Praecis Pharmaceuticals
|
Synthetic peptide that acts as a gonadotropin-releasing hormone antagonist
|
Palliative treatment of advanced symptomatic prostate cancer
|
11/03
|
|
Rebetol Oral Solution and Capsules
(ribavirin)
|
Schering-Plough; Valeant Pharmaceuticals International (Ribapharm)
|
Synthetic nucleoside analog (new formulation)
|
For use in combination with Intron A (interferon alpha-2b) to treat
chronic HCV infection in patients 3 years of age and older with compensated
liver disease previously untreated with alpha interferon
|
7/03
|
|
Risperdal Consta
(risperidone; long-acting injection)
|
Alkermes, Janssen Pharmaceutica Products (Johnson & Johnson)
|
Long-acting formulation of Risperdal that uses Alkermes' Medisorb drug-delivery
technology
|
Management of schizophrenia (twice-monthly injection)
|
10/03
|
|
Somavert
(pegvisomant)
|
Pfizer (Pharmacia; Sensus Drug Development); Nektar Therapeutics
|
PEGylated analog of human growth hormone that has been structurally
altered to act as a growth hormone (GH) receptor antagonist
|
Acromegaly
|
3/03
|
|
Striant
(testosterone buccal system)
|
Columbia Laboratories; Quintiles Transnational
|
Testosterone (delivered through a tablet adhered to the gums)
|
Hormone replacement in males
|
6/03
|
|
Velcade
(bortezomib; formerly MLN341, LDP-341 and PS-341)
|
Millennium Pharmaceuticals (LeukoSite, ProScript)
|
Proteasome inhibitor; small molecule drug that blocks the enzyme complex
(proteasome) that exists in all cells and plays an important role in
numerous biological pathways, including growth of cancer cells
|
Relapsed and refractory multiple myeloma
|
5/03
|
|
Zavesca
(OGT 918; miglustat)
|
Celltech Group (Oxford GlycoSciences); Actelion
|
Small molecule inhibitor of glycosyltransferase (inhibits glycolipid
formation)
|
Adults with type I Gaucher disease for whom enzyme replacement therapy
is not an option (oral administration)
|
8/03
|
* Includes drugs developed by biotechnology companies as well as those developed by pharmaceutical companies that are considered relevant to the industry.
However, biologics will always remain an essential component of the physician’s armamentarium. We’ve already mentioned the wide use of Epogen, Procrit, Enbrel and Remicade – and these important therapies are far from the only biologics on the market. (For a list of some of the other big sellers, click here.)
And many of the biologics approved in 2003 should find rapid acceptance by the medical community, too. These certainly include Amevive and Raptiva. As well, Xolair -- the new biological therapy for allergic asthma developed by Genentech, Tanox Inc. and Novartis – addresses a very large population of sufferers (about 500,000 in the U.S. alone).
Biotech And Biotech-Related Biologics Approved In 2003*: First-Time Approvals
|
Product Name
|
Company (s) (Developer; Marketer)
|
Product Description
|
Indication
|
Approval Date
|
|
ADVATE
(antihemophilic factor [recombinant], plasma/albumin-free method)
(rAHF-PFM)
|
Baxter Healthcare
|
Recombinant Factor VIII produced without added human or animal plasma
proteins or albumin
|
Prevention and control of bleeding episodes in patients with hemophilia
A
|
7/03
|
|
Aldurazyme
(laronidase)
|
BioMarin Pharmaceutical, Genzyme
|
Recombinant human alpha-L-iduronidase
|
Enzyme replacement therapy for patients with Hurler syndrome (mucopolysaccharidosis;
MPS I)
|
4/03
|
|
Amevive
(alefacept)
|
Biogen
(now Biogen Idec)
|
Fusion protein; human LFA-3 IgG1 fusion protein (a.k.a., LFA3TIP) (targets
CD45RO+ T cells)
|
Treatment of adult patients with moderate-to-severe chronic plaque
psoriasis who are candidates for systemic or phototherapy (IV or IM)
|
1/03
|
|
Bexxar
(tositumomab and iodine I 131 tositumomab)
|
Corixa (Coulter Pharmaceutical); GlaxoSmithKline
|
Murine monoclonal antibody against CD20 antigen on B cells, conjugated
to I-131
|
Patients with CD20-positive non-Hodgkin’s lymphoma, with and without
transformation, whose disease is refractory to rituximab and has relapsed
following chemotherapy
|
6/03
|
|
Fabrazyme
(agalsidase beta)
|
Genzyme
|
Recombinant human alpha-galactosidase A
|
Enzyme replacement therapy for patients with Fabry disease
|
4/03
|
|
FluMist
(influenza virus vaccine live, intranasal)
|
MedImmune (Aviron); Wyeth-Lederle Vaccines
|
Attenuated, cold-adapted live virus vaccine (intranasal)
|
To prevent influenza in healthy people between the ages of 5 and 49
|
6/03
|
|
Raptiva
(formerly Xanelim; efalizumab)
|
Genentech; Xoma; Serono
|
Humanized MAb targeted to T cells (anti CD11a); reversibly blocks activation,
reactivation and trafficking of T cells
|
Chronic moderate to severe plaque psoriasis (once-weekly subcutaneous
injection)
|
10/03
|
|
Xolair
(a.k.a. Anti-IgE, rhuMAb-E25; omalizumab)
|
Genentech, Tanox, Novartis Pharmaceuticals
|
Recombinant humanized anti-IgE monoclonal antibody
|
Moderate to severe persistent allergic asthma in adults and adolescents
whose symptoms are inadequately controlled with corticosteroids
|
6/03
|
* Includes recombinant proteins, monoclonal antibodies and vaccines developed by biotechnology companies as well as biotech-derived products developed by pharmaceutical companies.
Moreover, there are now three new medications for individuals afflicted with rare genetic disorders – and two are enzyme replacement regimens that represent the first real therapies for these diseases. BioMarin Pharmaceutical Inc. and Genzyme Corp.’s Aldurazyme treats Hurler syndrome (mucopolysaccharidosis); and Genzyme’s Fabrazyme treats the potentially fatal lipid storage disorder Fabry disease. As well, patients suffering from the genetic disorder hemophilia A (about 13,500 in the U.S.) can now use Baxter International Inc.’s recombinant factor VIII product Advate, which has been produced without added human or animal plasma proteins or albumin, thus increasing the drug’s safety profile.
The third product treats patients with Gaucher disease who are not eligible for enzyme replacement therapy. Developed by Oxford GlycoSciences plc (which was acquired by Celltech Group plc in July 2003), Zavesca is a small molecule inhibitor of glycosyltransferase.
Also joining the roster of new biologics are Corixa Corp.’s non-Hodgkin’s lymphoma therapy Bexxar and MedImmune Inc.’s intranasal flu vaccine FluMist – both of which suffered excruciatingly long journeys through the FDA's approval process.
Last year also saw the approval of the first NMDA receptor antagonist for treating Alzheimer’s disease. Importantly, Namenda (developed by Merz + Co., Neurobiological Technologies Inc. and Forest Laboratories Inc.) is the only approved drug for treating moderate-to-severe Alzheimer’s – the most difficult stages of this terrible affliction.
In the greater scheme of things, the FDA approved a total of 35 new medicines (drugs and biologics) in 2003, according to the Pharmaceutical Research and Manufacturers of America (PhRMA). And biotech companies’ therapeutics constituted 50 percent of them, according to this organization’s tally. That’s an impressive gain over 2002, when biotech firms’ therapeutics constituted about one-quarter of newly approved medicines listed on PhRMA’s annual roster. (This 50 percent figure may be a little off, since PhRMA – which clearly states that its information may not be comprehensive – cited 17 biotech-related products while we found 25. Conversely, we don’t track the vast majority of big pharma-sponsored drug approvals. Nonetheless, the basic fact remains: Biotech-derived therapeutics have become a major component of all new medicines.)
Of the 17 new biotech products included on PhRMA’s list, most drugs and biologics were sponsored by biotech firms per se (please refer to the tables), but two of the biologics sponsored by big pharma actually came from biotech firms.
Baxter’s Advate, for instance, contains the same recombinant Factor VIII that was originally developed by Genetics Institute Inc. and approved for marketing in December 1992 as Recombinate. (In fact, Baxter markets Recombinate.) And the NDA for Pfizer Inc.’s PEGylated human growth hormone analog Somavert was already filed by its developer, Sensus Drug Development Corp., when Pfizer (Pharmacia at the time) acquired the company in March 2001.
As well, the PhRMA survey says that the FDA approved an additional 51 medicines for new indications – bringing the total to 86 approvals in 2003.
Biotech and biotech-related products also constituted a significant proportion of the marketed medicines that garnered approvals in new indications: 13 therapies won further approvals in 2003.
§ Avonex. Biogen Idec’s multiple sclerosis (MS) therapy (recombinant interferon beta-1a) was approved in February for treating patients after their first attack. First approved in May 1996, the product could only be prescribed after a patient had experienced at least two attacks. The new label, however, allows physicians to initiate therapy at an earlier stage in the disease’s progression. Avonex can now be bought in a prefilled syringe, too, an approval that came in May.
§ Betaseron. Chiron Corp.’s MS therapy (recombinant interferon beta-1b) also won further approval: In March, the FDA approved expanded labeling that allows the product’s use to reduce the frequency of clinical exacerbations in patients with relapsing MS. In October, the FDA approved a prefilled diluent syringe, making it easier for patients to prepare their medication.
§ Eligard. Atrix Laboratories Inc.’s prostate cancer drug was approved in February in a four-month sustained-release version. The product was first approved in January 2002 in a one-month sustained-release formulation and then in a three-month formulation in July 2002.
§ Enbrel. The market for Amgen Inc.’s breakthrough product for treating rheumatoid arthritis (RA) keeps on expanding. In July 2003, Enbrel was approved for improving physical function in patients with moderately to severely active RA. In August, the FDA approved Enbrel for inhibiting the progression of structural damage in patients with psoriatic arthritis. And in July, Enbrel was approved for treating ankylosing spondylitis, a rheumatic disease that affects the spine. To top it off, in October the FDA approved a once-weekly formulation of Enbrel, which can be used across all indications.
§ Factive. GeneSoft Pharmaceuticals Inc. won first-time approval for its antibiotic to treat pneumonia and bronchitis in April 2003. The FDA also approved the drug for treating community acquired pneumonia caused by multidrug-resistant strep in July.
§ Ganite. Genta Inc. received marketing approval for Ganite, for treating cancer-related hypercalcemia, in September 2003. However, the product was already approved for marketing when Genta acquired a patent portfolio of gallium-containing compounds from Relgen LLC in April 2000. Genta re-manufactured the drug, re-activated the NDA in January and re-launched the product.
Biotech And Biotech-Related Products Under FDA Review 2003*
|
Product Name
|
Company (s)
(Developer; Marketer)
|
Product Description
|
Indication (Sought)
|
Submission Type
(Date)
|
Current Review Status
|
|
Actiza
(clindamycin phosphate foam, 1%)
|
Connetics
|
New foam formulation of antibiotic clindamycin
|
Topical treatment for acne
|
NDA
(12/03)
|
------
|
|
Angiomax
(bivalirudin)
|
The Medicines Co.
|
Synthetic thrombin inhibitor based on hirudin (natural anticoagulant
secreted by leeches)
|
Percutaneous coronary intervention (label amendment)
|
sNDA
(8/03)
|
------
|
|
Anidulafungin
|
Vicuron Pharmaceuticals
|
Anti-fungal agent (echinocandin)
|
Esophageal candidiasis
|
NDA
(4/03)
|
PDUFA date extended by 90 days, to 5/25/04
(1/04)
|
|
ARILVAX
|
Acambis; Chiron Vaccines
|
Live attenuated vaccine derived from the 17D yellow fever virus strain
|
Vaccine to prevent yellow fever
|
BLA
(12/03)
|
------
|
|
Avastin
(bevacizumab)
|
Genentech
|
Humanized antibody to vascular endothelial growth factor (VEGF)
|
First-line treatment of metastatic colorectal cancer (used with IFL
chemotherapy regimen)
|
Rolling BLA
(completed 9/03)
|
BLA accepted for filing and granted priority review
(12/03)
|
|
Calcitonin Nasal Spray
|
Nastech Pharmaceutical
|
Salmon calcitonin
|
Osteoporosis
|
ANDA
(12/03)
|
------
|
|
Campath
(alemtuzumab)
|
Ilex Oncology; Berlex Laboratories (Schering AG)
|
Humanized monoclonal antibody against CD52 antigen on T and B cells
|
To incorporate long-term efficacy and safety data in label on approved
product
|
sBLA
(5/02)
|
------
|
|
Cinacalcet HCl
|
NPS Pharmaceuticals; Amgen
|
Small molecule that modulates the behavior of the calcium-sensing receptor
on the parathyroid gland (calcimimetic)
|
Treatment of secondary hyperparathyroidism in patients with chronic
kidney disease
|
NDA
(9/03)
|
------
|
|
Clofarabine
|
ILEX Oncology; Bioenvision
|
Next-generation purine nucleoside antimetabolite
|
Refractory or relapsed acute lymphoblastic leukemia in children
|
Rolling NDA
(10/03 – 1H04E)
|
------
|
|
DepoMorphine
|
Endo Pharmaceuticals; SkyePharma
|
Sustained-release liposome injection of morphine sulfate
|
Epidural analgesic for pain relief after surgery
|
NDA
(7/03)
|
NDA accepted for filing
(9/03)
|
|
Diquafosol
(a.k.a. INS365)
|
Inspire Pharmaceuticals; Allergan
|
P2Y2 receptor agonist (dinucleotide) that activates receptors on the
surface and inner lining of the eyelid
|
Dry eye
|
NDA
(6/03)
|
Approvable letter requesting an additional clinical study (12/03);
FDA reiterated its requirement for a new trial (1/04)
|
|
Dynepo
(gene-activated EPO)
|
Transkaryotic Therapies; Aventis Pharma
|
Human erythropoietin produced via gene activation (inserts DNA sequences
into human cells, thus activating the endogenous human gene to stimulate
EPO production)
|
Anemia in patients with chronic renal failure (both dialysis and non-dialysis
patients)
|
BLA
(8/00)
|
FDA did not accept BLA for filing (11/00); Aventis has not yet submitted
new BLA, due to patent litigation with Amgen, which is still ongoing
|
|
Enbrel
(etanercept)
|
Amgen (Immunex); Wyeth
|
Dimeric fusion protein; recombinant soluble p75 tumor necrosis factor
receptor (TNFr) linked to Fc portion of human IgG1
|
Moderate to severe plaque psoriasis
|
sBLA
(7/03)
|
------
|
|
Erbitux
(cetuximab)
|
ImClone Systems; Bristol-Myers Squibb
|
IgG1 chimeric monoclonal antibody to the epidermal growth factor receptor
(EGFR)
|
Combination therapy with irinotecan for treating patients with EGFR-expressing
irinotecan-refractory metastatic colorectal cancer
|
BLA (new)
(8/03)
|
BLA accepted for filing and review
(10/03)
|
* Includes drugs and biologics developed by biotechnology companies as well as biotech-derived products developed by pharmaceutical companies.
§ Gleevec. Novartis’ oral cancer drug garnered an additional approval in May 2003. The FDA approved Gleevec for use in pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML). This is the fourth indication for Gleevec: The FDA initially approved the drug in May 2001 for treating patients with advanced stages of CML. In 2002, Gleevec was approved for treating inoperable and/or metastatic gastrointestinal stromal tumors (February) and as a first-line therapy for patients with newly diagnosed CML (December).
§ Gliadel Wafer. Guilford Pharmaceuticals Inc. finally won approval in February to sell its implantable chemotherapy wafer as a first-line therapy for patients with newly diagnosed brain cancer. The product was first approved in September 1996 for use as an adjunct to surgery to prolong survival in patients with recurrent brain cancer.
§ Photofrin. Axcan Pharma Inc. acquired this photodynamic therapy from QLT Inc. in June 2000. The product gained its first FDA approval in November 1995 -- for treating esophageal cancer -- and its newest in August 2003 – for the ablation of high grade dysplasia in Barrett’s esophagus patients.
§ Remicade. This monoclonal antibody to tumor necrosis factor-alpha, developed by Centocor (a Johnson & Johnson company), garnered yet one more approval in 2003. In April, Remicade was approved for long-term use in fistulizing Crohn’s disease using 8-week maintenance dosing. The FDA initially approved the product in August 1998 for treating Crohn’s disease; it was also approved in November 1999 for reducing the signs and symptoms of RA in patients who have had an inadequate response to methotrexate; in January 2001 as a combination therapy with methotrexate for inhibiting the progression of structural damage in RA patients; in February 2002 for use in combination with methotrexate to improve physical function in patients with RA; and in July 2002 to reduce and maintain clinical remission in Crohn’s disease patients.
§ Synagis: MedImmune won an expanded label for its anti-respiratory syncytial virus (RSV) therapy in September 2003. The product can now be used in children with congenital heart disease to prevent hospitalization caused by RSV infection. Synagis was originally approved in June 1998 for preventing the infection in high-risk pediatric patients.
§ Rebif. Serono S.A. got the nod in May 2003 to add additional efficacy and product stability information to the label for Rebif, its interferon beta-1a therapy which was first approved in March 2002 for treating relapsing remitting MS.
§ Zorbtive. Serono’s recombinant human growth hormone, which is already sold as Serostim for treating AIDS wasting, was approved in December as a therapy for short bowel syndrome.
Biotech And Biotech-Related Products Under FDA Review 2003*
|
Product Name
|
Company (s)
(Developer; Marketer)
|
Product Description
|
Indication (Sought)
|
Submission Type
(Date)
|
Current Review Status
|
|
Estorra
|
Sepracor
|
Eszopiclone (oral, non-benzodiazepine hypnotic)
|
Transient and chronic insomnia
|
NDA
(1/03)
|
PDUFA date extended for 90 days, to 2/29/04
(11/03)
|
|
Extina
(ketoconazole 2%)
|
Connetics
|
Foam formulation of antifungal drug
|
Seborrheic dermatitis
|
NDA
(7/03)
|
------
|
|
Fortical
|
Unigene Laboratories; Upsher-Smith Laboratories
|
Calcitonin nasal spray
|
Osteoporosis
|
NDA
(3/03)
|
Approvable letter requesting additional information and data
(1/04)
|
|
Fortigel
(formerly Tostrex; testosterone gel)
|
Cellegy Pharmaceuticals; PDI
|
Testosterone gel
|
Transdermal testosterone replacement therapy for male hypogonadism
|
NDA
(6/02)
|
Non-approvable letter
(7/03)
|
|
Fosrenol
(formerly Foznol)
|
AnorMED; Shire Pharmaceuticals Group
|
Lanthanum carbonate
|
To treat high phosphate levels in the blood of patients undergoing
dialysis as a result of chronic kidney failure
|
NDA
(4/02)
|
Approvable letter requesting additional data and analysis
(3/03)
|
|
Genasense
(oblimersen sodium)
|
Genta; Aventis
|
Antisense oligonucleotide that directly targets apoptosis pathway;
inhibits production of Bcl-2
|
Advanced malignant melanoma (in combination with chemotherapy)
|
Rolling NDA
(9/03 – 12/03)
|
------
|
|
Hemopure
(hemoglobin glutamer -250 [bovine])
|
Biopure
|
Chemically stabilized bovine hemoglobin formulated in balanced salt
solution
|
Treatment of signs and symptoms of acute anemia in adult patients undergoing
orthopedic surgery; to eliminate, delay or reduce the need for red blood
cells in these patients
|
BLA
(7/02)
|
FDA completed review and requested additional information (but not
more trials)
(8/03);
agency raised additional issues and will determine if more trials are
needed
(1/04)
|
|
Humira
(formerly D2E7; adalimumab)
|
Cambridge Antibody Technology; Abbott Laboratories (Knoll/BASF)
|
Fully human monoclonal antibody to tumor necrosis factor-alpha
|
To improve physical function in patients with moderately to severely
active rheumatoid arthritis
|
sBLA
(10/03)
|
------
|
|
Hylaform
(hylan-B gel)
|
Genzyme; Inamed
|
Hyaluronic acid-based cosmetic dermal filler
|
Soft tissue contour deficiencies (wrinkles)
|
PMA
(8/03)
|
General and Plastic Surgery Devices Panel voted 6-3 to recommend approval
(11/03)
|
|
InductOs
(rhBMP-2/ACS)
|
Wyeth (Genetics Institute)
|
Recombinant human bone morphogenetic protein-2 (rhBMP-2) applied to
an absorbable collagen sponge (ACS)
|
Treatment of open long-bone fractures
|
PMA
(12/00)
|
Medical Devices Advisory Committee recommended approval, with conditions
(11/02)
|
|
Istalol
(timolol)
|
ISTA Pharmaceuticals, Senju Pharmaceutical Co.
|
New formulation of timolol (non-selective beta adrenergic receptor
blocking agent, a.k.a. beta blocker)
|
Glaucoma (once-daily topical formulation)
|
NDA
(9/02)
|
Approvable letter
(7/03)
|
|
Kineret
(anakinra)
(formerly Antril, Synergen)
|
Amgen
|
Recombinant interleukin-1 receptor antagonist
|
To inhibit the progression of structural damage in adult patients with
moderately to severely active rheumatoid arthritis
|
sBLA
(10/02)
|
------
|
|
LeuTech
|
Palatin Technologies, Mallinckrodt
|
Radiolabeled monoclonal antibody that binds specifically to white blood
cells; for in vivo imaging of infection sites
|
Diagnosis of appendicitis in patients with equivocal signs and symptoms
|
BLA
(11/99)
|
Company started filing BLA amendments in 1H03 and anticipates completing
the process in 1Q04 (9/03)
|
* Includes drugs and biologics developed by biotechnology companies as well as biotech-derived products developed by pharmaceutical companies.
In 2003, biotech companies also won approvals for four HIV assays, one in vitro diagnostic for Hepatitis B virus, one assay for predicting the risk of coronary heart disease and two products for filling wrinkles.
§ OraQuick Rapid HIV-1. This rapid (20 minute) point-of-care test that detects antibodies to HIV-1 in fingerstick whole blood was developed by OraSure Technologies. It was first approved in November 2002 for use by certified labs. In January 2003, the test garnered a CLIA waiver to allow its use in a broad setting, including clinics, doctor’s offices and counseling centers. In September, the assay was also approved for detecting the antibodies in venipuncture whole blood.
§ Uni-Gold Recombigen HIV Test. Developed by Trinity Biotech plc, this immunoassay is even more rapid than OraQuick, delivering results in 10 minutes. In December, the FDA approved its use for detecting antibodies to HIV in serum, plasma or whole blood.
§ ViroSeq. Celera Diagnostics’ HIV-1 genotyping system was initially cleared for marketing in December 2002 for use as an aid in monitoring and treating HIV infection. The in vitro diagnostic sequencing-based test detects mutations in the HIV genome that confer drug resistance. In 2003, Celera gained two more approvals for the test: It can now be used by mid-sized reference labs (along with Applied Biosystems’ mid-sized DNA analyzer; approved in January) as well as by the largest clinical testing labs (when paired with ABI’s large-scale, high throughput DNA analyzer; approved in June).
§ HbsAg Assays. Bio-Rad Laboratories Inc. won approval in April for its immunoassays for the screening and confirmation of HBV in the donor blood supply (Genetic Systems HbsAg EIA 3.0 and HbsAg Confirmatory Assay 3.0).
§ PLAC Test. Developed by diaDexus Inc., this immunoassay measures the level of lipoprotein-associated phospholipase A2 in blood. It was cleared for marketing in July for use as an aid in predicting an individual’s risk for heart disease.
§ CosmoDerm/CosmoPlast. Inamed Corp.’s products, which contain Advanced Tissue Sciences Inc.’s human-based collagen, were approved in March for use as dermal fillers for facial wrinkles and other soft tissue contour deficiencies.
There’s no question that some of the therapies approved in 2003 will become best-sellers in time. These are bound to include Amevive, Raptiva, Xolair, Cialis and Namenda – all of which address the needs of large patient populations.
But there’s also plenty of reason to be excited about some of the products still under review. For instance, everyone’s waiting for the FDA to approve Genentech’s cancer therapy Avastin, a humanized antibody to vascular endothelial growth factor (VEGF). It’s the first-in-class of a new type of targeted cancer therapy – one that cuts off the blood supply to tumors – and demonstrated stunningly positive results (when used in combination with chemotherapy) in a Phase III clinical trial in metastatic colorectal cancer.
Biotech And Biotech-Related Products Under FDA Review 2003*
|
Product Name
|
Company (s)
(Developer; Marketer)
|
Product Description
|
Indication (Sought)
|
Submission Type
(Date)
|
Current Review Status
|
|
Loteprednol etabonate and tobramycin ophthalmic suspension
|
Pharmos; Bausch & Lomb
|
Corticosteroid (anti-inflammatory) -antibiotic combination
|
Patients with steroid-responsive inflammatory ocular conditions who
have or who are at risk of developing bacterial ocular infections
|
NDA
(NA)
|
NDA accepted for filing
(11/03)
|
|
Luveris
(lutropin alpha)
|
Serono
|
Recombinant form of luteinizing hormone
|
Stimulation of follicular development in infertile women with profound
luteinizing hormone deficiency
|
BLA
(2001)
|
Reproductive Health Drugs Advisory Committee voted 11-3 to support
follicular indication but split on indication of ovulation induction
(9/03)
|
|
Onco TCS
|
Inex Pharmaceuticals; Enzon Pharmaceuticals
|
Liposome- encapsulated vincristine (transmembrane carrier system)
|
Relapsed aggressive non-Hodgkin’s lymphoma
|
Rolling NDA
(9/03 – 1Q04E)
|
------
|
|
Metvix PDT
(methyl aminolevulinate)
|
PhotoCure; Galderma
|
Photodynamic therapy
|
Basal cell carcinoma
|
NDA
(2/03)
|
Dermatologic and Ophthalmic Drugs Advisory Committee voted 9-3 against
recommending approval
(9/03)
|
|
MS-325
|
EPIX Medical; Schering AG
|
Imaging contrast agent (in vivo binding of contrast agent to proteins
and other key receptor molecules)
|
Magnetic resonance angiography (imaging to detect vascular disease)
|
NDA
(12/03)
|
------
|
|
MT-100
|
Pozen
|
Metoclopramide HCl combined with naproxen sodium
|
First-line therapy for acute treatment of migraine (oral)
|
NDA
(7/03)
|
NDA accepted for filing
(10/03)
|
|
MT-300
|
Pozen; Xcel Pharmaceuticals
|
Dihydroergotamine mesylate
|
Long-lasting pain relief for migraine (injection)
|
NDA
(12/02)
|
Not approvable letter
(10/03)
|
|
Nabi-HB
|
Nabi Biopharmaceuticals
|
Hepatitis B immune globulin (human)
|
To prevent liver transplant patients from becoming re-infected with
HBV (intravenous injection)
|
BLA
(11/02)
|
Complete response letter, requesting additional information
(6/03);
NABI submitted supplemental data
(8/03)
|
|
Nascobal Nasal Spray
(cyanocobalamin)
|
Questcor Pharmaceuticals; Nastech Pharmaceutical
|
Vitamin B-12
|
Vitamin B-12 deficiency
|
NDA
(12/03)
|
------
|
|
Orathecin
(rubitecan)
|
SuperGen
|
Topoisomerase I inhibitor extracted from bark and leaves of Camptotheca
acuminate tree
|
Pancreatic cancer refractory to available therapies (oral)
|
Rolling NDA
(12/02 – 1/04)
|
------
|
|
ORTHOVISC
(sodium hyaluronate)
|
Anika Therapeutics; Ortho Biotech
|
Highly purified, high molecular weight naturally derived hyaluronic
acid
|
Osteoarthritis of the knee (viscosupplementation and pain relief)
|
Rolling PMA
(NA – 6/03)
|
Approvable letter, subject to successful FDA inspection of manufacturing
facility
(12/03)
|
|
Oxymorphone ER
and
Oxomorphone IR
|
Endo Pharmaceuticals; Penwest Pharmaceuticals
|
Opioid analgesic (extended-release tablets and immediate-release tablets)
|
Relief of moderate-to-severe pain
|
NDAs
(12/02)
|
Approvable letters requesting additional trials
(10/03)
|
|
Oxyprim
(oxypurinol)
|
Cardiome Pharma
|
Xanthine oxidase inhibitor (inhibits formation of uric acid)
|
Allopurinol-intolerant hyperuricemia (gout)
|
NDA
(12/03)
|
------
|
* Includes drugs and biologics developed by biotechnology companies as well as biotech-derived products developed by pharmaceutical companies.
People are also curious to learn how the FDA will view the newly submitted clinical data on ImClone Systems Inc.’s anti-EGFR therapy Erbitux. The company, the CEO, and the product itself gained infamy several years ago and none has managed to avoid the spotlight since. Yet, Erbitux has been approved in Switzerland -- ImClone’s European partner Merck KGaA garnered marketing approval for the drug in December 2003 – and ImClone’s incorporated Merck’s clinical trial results into its BLA.
Avastin and Erbitux are among the 56 product submissions pending at the FDA at the end of 2003. In the new year, two of those applications have already received the agency’s blessing: Cephalon Inc.’s marketed narcolepsy drug Provigil was approved in January for improving wakefulness in patients with sleep apnea and shift work sleep disorder, too. And Anika Therapeutics Inc.’s hyaluronic acid-based product Orthovisc was approved in early February for treating osteoarthritis of the knee.
But, as evidenced by the tables in this article, there are still 34 NDAs, 9 BLAs, 4 PMAs and 6 supplemental applications (sNDA, sBLA, and ANDA) in the final stages of review. If even half of those get approved in 2004, it will be another outstanding year for biotech.
Biotech And Biotech-Related Products Under FDA Review 2003*
|
Product Name
|
Company (s)
(Developer; Marketer)
|
Product Description
|
Indication (Sought)
|
Submission Type
(Date)
|
Current Review Status
|
|
PolyHeme
|
Northfield Laboratories
|
Chemically modified hemoglobin derived from outdated donor blood
|
Oxygen-carrying blood substitute for treating severely injured trauma
patients before they reach a hospital
|
BLA
(8/01)
|
Company cleared to proceed with trial
(3/03)
|
|
Prestara
(formerly Aslera; GL701)
(prasterone)
|
Genelabs Technologies; Watson Pharmaceuticals; Tanabe Seiyaku
|
Adrenal hormone (dehydroepiandrosterone [DHEA])
|
To limit bone loss in women with mild to moderate systemic lupus erythematosus
who are taking low-dose glucocorticoids
|
Rolling NDA
(5/00-9/00)
|
Confirmatory trial requested by FDA still ongoing
(9/03)
|
|
Provigil
(modafinil)
|
Cephalon
(Group Lafon)
|
Synthetic compound that is thought to affect alpha-adrenergic receptors
in the brain
|
To improve wakefulness in patients with excessive sleepiness associated
with obstructive sleep apnea and shift work sleep disorder
|
sNDA
(12/02)
|
Approved for marketing
(1/04)
|
|
Ranexa
(ranolazine)
|
CV Therapeutics
(product acquired from Syntex)
|
Partial fatty acid oxidation (pFOX) inhibitor
|
Chronic angina
|
NDA
(12/02)
|
Cardiovascular and Renal Drugs Advisory Committee evaluated drug but
did not vote; committee indicated more trials are needed
(12/03)
|
|
Replagal
(agalsidase alfa)
|
Transkaryotic Therapies; Sumitomo Pharmaceuticals
|
Recombinant human alpha galactosidase A
|
Enzyme replacement therapy for Fabry disease
|
BLA
(6/00)
|
TKT announced that it is ending its efforts to seek US approval of
this product
(1/04)
|
|
Rifaximin
|
Salix Pharmaceuticals
|
Non-systemic, gastrointestinal site-specific antibiotic
|
Travelers’ diarrhea
|
NDA
(12/01);
amendment to NDA
(11/03)
|
Amendment to NDA is considered a complete response; PDUFA goal date
is 5/26/04
(12/03)
|
|
Riquent
|
La Jolla Pharmaceutical
|
Toleragen (an epitope-presenting carrier molecule) that binds to the
surface of B cells and reduces levels of antibodies to dsDNA
|
Treatment of patients with systemic lupus erythematosus at risk of
renal disease
|
NDA
(12/03)
|
------
|
|
RSR13
(efaproxiral)
|
Allos Therapeutics
|
Radiation sensitizer; synthetic small molecule that sensitizes oxygen-deprived
tumor tissue
|
Treatment of brain metastases in patients with breast cancer (adjunct
to whole brain radiation therapy)
|
Rolling NDA
(8/03 – 12/03)
|
NDA accepted for filing under priority review
(2/04)
|
|
Sodium hyaluronate
|
Savient Pharmaceuticals
|
High molecular weight formulation of hyaluronate for viscosupplementation
|
Treatment of pain associated with osteoarthritis of the knee
|
PMA
(5/01)
|
Approvable letter
(10/03)
|
|
Symlin
(pramlintide acetate)
|
Amylin Pharmaceuticals
|
Synthetic version of human hormone amylin
|
Adjunctive therapy to insulin for treating people with Type I and insulin-using
type II diabetes
|
NDA
(12/00):
amendment to NDA
(6/03)
|
FDA issued second approvable letter, but requested additional clinical
data
(12/03)
|
|
TAXUS Express2
|
Angiotech Pharmaceuticals; Boston Scientific
|
Polymer-based, paclitaxel-eluting coronary stent
|
To reduce coronary restenosis
|
Rolling PMA
(2/03 – 6/03)
|
Circulatory System Devices Advisory Panel unanimously recommended approval
(11/03)
|
|
Trospium
|
Indevus Pharmaceuticals
|
Muscarinic receptor antagonist (anticholinergic compound that relaxes
smooth muscles)
|
Overactive bladder
|
NDA
(4/03)
|
NDA accepted for review
(6/03)
|
|
Vidaza
(azacitidine)
|
Pharmion
|
Azacitidine (demethylating agent that reactivates suppressor genes)
|
Myelodysplastic syndromes
|
NDA
(12/03)
|
------
|
|
Vitrase
|
ISTA Pharmaceuticals; Allergan
|
Highly purified hyaluronidase (ovine)
|
Severe vitreous hemorrhage
|
Rolling NDA
(1/02 – 1Q03)
|
Approvable letter requesting an additional clinical trial
(4/03)
|
|
Vitrase
|
ISTA Pharmaceuticals; Allergan
|
Highly purified hyaluronidase (ovine)
|
For use as a spreading agent to facilitate the dispersion and absorption
of other drugs
|
NDA
(8/03)
|
NDA accepted for filing with priority review
(8/03; 10/03)
|
* Includes drugs and biologics developed by biotechnology companies as well as biotech-derived products developed by pharmaceutical companies.
|