FDA Approvals: Asmanex Twisthaler, Fosamax Plus D, Velcade

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FDA Approvals: Asmanex Twisthaler, Fosamax Plus D, Velcade

Yael Waknine

Medscape Medical News 2005. © 2005 Medscape

April 14, 2005 — The U.S. Food and Drug Administration (FDA) has

approved mometasone furoate inhalation powder for the maintenance

treatment of asthma as prophylactic therapy in patients aged 12 years

and older, and to reduce or eliminate the need for corticosteroid

therapy in patients with asthma requiring such treatment; alendronate

sodium plus cholecalciferol tablets for the treatment of osteoporosis

in postmenopausal women, and to increase bone mass in men with

osteoporosis; and an expanded indication for bortezomib injection,

allowing its use in the second-line treatment of multiple myeloma.

Mometasone Furoate Inhalation Powder (Asmanex Twisthaler) for Asthma

On March 30, the FDA approved mometasone furoate inhalation powder

(Asmanex Twisthaler 220 µg, made by Schering-Plough Corp) for the

first-line maintenance treatment of asthma as prophylactic therapy in

patients aged 12 years and older. It is also indicated for use in

patients with asthma requiring oral corticosteroid therapy when its

addition to the therapeutic regimen may reduce or eliminate the need

for oral corticosteroids.

The device is inhalation-activated rather than propellant-driven, and

it features a numeric dose counter that displays remaining doses.

The approval was based on the results of three-month, double-blind,

randomized clinical trials in patients aged 12 years and older showing

that use of the product significantly improved lung function, decreased

use of rescue medication (albuterol), decreased incidence of nighttime

awakenings, and improved daytime symptoms such as coughing and wheezing

compared with placebo.

The recommended starting dose for mometasone furoate powder is one

inhalation daily in the evening for patients previously treated with

bronchodilators alone or inhaled corticosteroids. For patients

previously maintained on oral corticosteroids, the recommended starting

dose is two inhalations twice daily.

Alendronate Plus Vitamin D3 Supplement (Fosamax Plus D) for Osteoporosis

On April 7, the FDA approved alendronate sodium plus cholecalciferol

(vitamin D3) tablets (Fosamax Plus D, made by Merck & Co) for the

treatment of osteoporosis in postmenopausal women and to increase bone

mass in men with osteoporosis.

The approval was based in part on the results of studies showing that

use of the product increased bone mass and significantly reduced the

risk of osteoporotic hip and spine fractures in women. Studies also

support an increase in bone mass for men, although the effect on

fracture incidence has not been determined.

The once-weekly tablet contains 70 mg of alendronate sodium and 2800 IU

(400 IU/day) of vitamin D3. The FDA recommended daily dose of vitamin

D3 is 400 to 800 IU.

The standard dosing regimen involves swallowing the tablet (no chewing

or sucking) with six to eight ounces of water upon rising, then

allowing 30 minutes to elapse in an upright position prior to food

consumption.

The most commonly reported adverse effects in clinical studies of the

product included abdominal pain (3.7%), musculoskeletal pain (2.9%),

indigestion (2.7), regurgitation (1.9%), and nausea (1.9%).

Bortezomib (Velcade) for Second-Line Treatment of Multiple Myeloma

On March 25, the FDA approved an expanded indication for bortezomib

injection (Velcade, made by Millennium Pharmaceuticals, Inc), allowing

its use in the treatment of multiple myeloma (MM) in patients who have

received at least one prior therapy.

Bortezomib previously received accelerated approval in May 2003 for the

treatment of multiple myeloma in patients who had received a minimum of

two prior therapies and demonstrated disease progression on their last

therapy.

According to a company news release, the expanded indication is

expected to double the number of U.S. patients who could potentially

benefit from bortezomib therapy.

The approval was based on data from a multicenter, randomized, phase 3

trial (APEX) showing that second-line treatment with bortezomib was

associated with a significant increase in time to progression (P <

..0019), overall survival (P < .05), and response rate (P < .0035)

compared with high-dose dexamethasone during a mean follow-up period of

8.3 months.

Overall, a significantly greater proportion of patients receiving

bortezomib achieved a complete response (CR, 6% vs 2%) or near complete

response (nCR, 6% vs 2%) compared with high-dose dexamethasone.

Bortezomib therapy was associated with a 55% decrease in mortality rate

during the study.

The most commonly reported adverse events associated with bortezomib

(1.3 mg/m2 dose) included asthenic conditions (fatigue, malaise, and

weakness), diarrhea, nausea, constipation, peripheral neuropathy,

vomiting, pyrexia, thrombocytopenia, psychiatric disorders, and

anorexia.

Events were primarily mild in severity (grade 1 or 2) and were managed

by monitoring and dose modification when necessary.

Serious adverse events included pyrexia, diarrhea, dyspnea, pneumonia,

and vomiting.

Bortezomib (Velcade, made by Millennium and & ) was

approved for use in the European Union in April 2004 for the treatment

of relapsed and refractory multiple myeloma. It was approved in Canada

in January 2005 (made by Ortho-Biotech, a division of Janssen-Ortho,

Inc) for the treatment of patients with multiple myeloma who have

relapsed after first-line therapy and are refractory to their most

recent therapy.

Reviewed by D. Vogin, MD

http://www.medscape.com/viewarticle/503190