Preos, a new parathyroid hormone product for osteoporosis

[Guest guest]

Rheumawire

Mar 31, 2004

Preos, a new parathyroid hormone product for osteoporosis

Salt Lake City, UT - A new treatment for osteoporosis is nearing the

marketplace Preos® (NPS Pharmaceuticals) [1]. The product is a

recombinant version of parathyroid hormone (PTH) and so is very similar

to teriparatide (Forteo®, Lilly). Both products have an anabolic action

on bone they stimulate the formation of new bone, in contrast to the

other drugs that are currently available for osteoporosis, which act by

preventing its resorption.

In fact, the difference between the 2 products is only a few amino

acidsPreos is a full-length version of PTH, while Forteo is missing 1

last fragment. However, NPS appears to be making a concerted effort to

differentiate between the 2 products and is particularly emphasizing

Preos as an option for mild osteoporosis as well as for those with more

serious disease. So far, Forteo has been seen as an option for the more

extreme cases of osteoporosis or for those who haven't responded to

other treatments for the disease.

Yesterday, NPS announced successful results from a pivotal phase 3 trial

involving 2600 postmenopausal women with mild to moderate osteoporosis,

in which the drug reduced the incidence of new vertebral fractures (VFs)

and worsening of existing VFs. The company says it plans to file a new

drug application with the US FDA later this year.

A lead investigator involved in the trial, Dr (Helen

Hospital, West Haverstraw, NY and Columbia University, New York,

NY) says the results " are encouraging and indicate that this drug can

build healthy new bone and prevent the occurrence of first-time

vertebral fractures in women with mild to moderate osteoporosis. "

" As a clinician, I think this is very important, because the first

osteoporotic fracture is the best predictor of future osteoporotic

fractures, and so preventing that first fracture is likely to reduce the

severity of the disease, " commented during a company webcast to

announce the results. " Avoiding the first fracture is therefore an

important clinical goal. "

The phase 3 study, known as the Treatment of Osteoporosis with PTH (TOP)

trial, was conducted in postmenopausal women with low bone-mineral

density (BMD). Study participants had a mean pretrial vertebral T score

of -3.0, ie, the average BMD measurement was 3 standard deviations below

the mean BMD of healthy young women. Most of the women (81%) did not

have a vertebral fracture before entering the study.

All the study participants received daily supplements of calcium (700

mg) and vitamin D (400 IU) and were randomized to receive either Preos

(100 µg by subcutaneous injection) or placebo. The trial lasted for 18

months, but more than half of the participants (1700 women) have elected

to continue in an open-label follow-up study, in which all the

participants receive the drug.

An analysis of all patients receiving at least 1 dose of the drug or

placebo shows a statistically significant reduction in the relative risk

of VFs for patients in the treatment group vs placebo.

The reduction was even higher when the analysis excluded women who

already had a VF when they entered the studyamong participants with no

prior VF, the relative risk reduction for a new VF was 68% (p=0.006).

In addition, there was a significant increase in BMD in women taking

Preos compared with those on placebo (+7%, p<0.001).

A reduction in the relative risk for a VF was seen at 12 months into the

study, but this was not statistically significant. Also, the women

taking Preos had fewer total fractures than those in the placebo group,

but again the difference was not statistically significant.

NPS would not be drawn into commenting on how these results compare with

those seen with Forteo, emphasizing that the 2 drugs have been studied

in different patient populations. The majority of women in the Preos

trial had not suffered a vertebral fracture, whereas in the pivotal

study with Forteo, the entry criterion was a prior vertebral fracture.

In the Forteo study, the relative reduction in risk of a new VF was 65%

with the 20-µg dose that is currently marketed.

The most frequent adverse events with Preos were elevated levels of

calcium in both serum and urine. In the majority of these patients,

these values returned to normal on retest or on entering an algorithm

that allowed for a reduction of the daily calcium supplement or study

drug, as is customary in other studies with PTH-related compounds, the

company says in its press release.

There were more dropouts from the group taking the drug than those

taking placebo16% vs 10%, respectively, dropped out of the study because

of any side effect, and 9% vs 2%, respectively, dropped out because of

elevated calcium levels, headaches, nausea, dizziness, or vomiting.

These dropout rates were in the region that was expected and did not

adversely affect the results from the study, a company researcher

commented during the webcast.

Zosia Chustecka

Source

1. [News release]. NPS announces positive phase III study results for

PREOS® in women with osteoporosis. NPS Pharmaceuticals March 30, 2004.

Available at: http://www.npsp.com/news/releasetxt.php?ReqId=509707.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org