摘要:

Currently marketed inhibitors of bone resorption or stimulators of bone formation have significantly contributed to a better preventive and therapeutic approach to postmenopausal and senile osteoporosis. However, none of the available compounds has unequivocally demonstrated an ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once the disease is established. Therefore, several new medications are being developed, with the aim of providing a better risk-benefit profile and/or a more favourable cost-utility assessment than available drugs.Potential inhibitors of bone resorption include specific inhibitors of the osteoclast's proton pump, inhibitors of prostaglandins or nitric oxide donors. Stimulators of osteoblastic activity and subsequent bone formation might be obtained by strontium salts, peptides of the parathyroid hormone family, growth hormone and insulin-like growth factors or bone morphogenetic proteins. Most of these compounds are now undergoing phase II/III development programmes, and results evaluating their potential benefit should be available within 1 to 5 years.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All the drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for a full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&D InsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

ALX 111 [parathyroid hormone (1-84) - Allelix, recombinant human parathyroid hormone, rhPTH(1-84)] is full length, recombinant human parathyroid hormone. It has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant.Until 1994, Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis. Allelix was subsequently, until September 1998, collaborating with Astra of Sweden in developing ALX 111. Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent. However, Astra has returned all rights to ALX 111 to Allelix. Allelix has extended its ALX 111 manufacturing collaboration with Chiron Corporation in the Netherlands.Phase II clinical trials of ALX 111 for the treatment of osteoporosis have been completed in the US, Canada and the Netherlands. Phase III trials are to commence shortly.It has been recommended that ALX 111 should be given for 1 year in combination with an antiresorptive agent such as estrogen or a bisphosphonate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;CP 336156 is a potent, nonsteroidal, tissue-selective estrogen receptor modulator. It has the bone-sparing and cardioprotective effects of estrogen but lacks the uterine cancer risk. CP 336156 is being investigated in phase II studies with Pfizer in the US as an orally administered therapy for osteoporosis. Phase I trials of the drug have been completed in Europe.The discovery of CP 336156 resulted from a research collaboration between Pfizer and Ligand Pharmaceuticals. There was a contract dispute between the 2 companies relating to their research agreement. Under a settlement of litigation, Ligand is entitled to milestone and royalty payments. If Pfizer is successful in developing the drug through to regulatory approval in the US, Ligand could receive royalty revenues from CP 336156 as early as 2003 to 2004.CP 336156 is an orally active, selective estrogen receptor modulator with a close structural resemblance to levormeloxifene. In animal studies it shows high oral bioavailability, comparable cholesterol-lowering potency to droloxifene, and is a potent inhibitor of bone loss. Clinical efficacy data, when available, will provide a clearer definition of the worth of CP 336156 as a treatment for osteoporosis.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Ibandronic acid (BM 210955, RPR 102289A, methylpentylaminopropylidene, Bondronat®, Bonviva®) is a new potent third-generation bisphosphonate being developed by Boehringer Mannheim (Roche) and Galenus Mannheim. Another company, Ontogeny, also appears to be involved in the development of the drug. A former development collaboration with Rhône-Poulenc Rorer has been discontinued.Bisphosphonates are well tolerated and effective in lowering serum calcium levels in patients with tumour-associated hypercalcaemia. Bisphosphonates have also been shown to have an inhibitory effect on bone reabsorption. The mechanism of action of bisphosphonates in reducing bone resorption is unknown at present. It is possible that they may reduce osteoclast activity directly, or induce the production of an osteoclast-inhibiting factor by osteoblasts.Ibandronic acid has been launched in Austria, Denmark and Germany and is registered in the remainder of the European Union for the treatment of abnormally elevated serum calcium levels as a result of malignant tumours. Ibandronic acid is in phase III clinical trials in Russia and the US for the treatment of patients with bone disorders such as malignancy- and osteolysis-related hypercalcaemia and metastatic bone disease. It is also being evaluated in Europe for the treatment of Paget's disease (phase III), and is in phase III clinical trials in Europe and the US for the treatment of osteoporosis. In Japan, ibandronic acid is in phase II trials for the treatment of postmenopausal osteoporosis and metastatic bone disease.Compared with other available bisphosphonates, ibandronic acid offers excellent efficacy at very low doses, and greater convenience, since it can be administered in a shorter infusion. Oral or injected ibandronic acid is an effective treatment for osteoporosis and does not produce significant toxicity.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Risedronic acid (NE 58095; risedronate sodium) is a bisphosphonate that is active after oral or parenteral administration. Procter and Gamble, the originator, has formed a global alliance with Hoechst Marion Roussel to commercialise risedronic acid (Actonel®). Both companies will be involved in completing clinical trials, seeking regulatory approval and preparing marketing plans for the launch of Actonel® for the treatment of bone disorders in all countries except Japan. Hoechst Marion Roussel will make milestone payments to Procter and Gamble and both companies will share revenues and expenses for Actonel®. The 2 companies will copromote Actonel® in North America and in selected key European markets, while Hoechst Marion Roussel will market the product independently in most other world markets.The first launch of risedronic acid was in the US for the treatment of Paget's disease. Filings for regulatory approvals were made in December 1998 in both the US and Europe for risedronic acid as a treatment and preventative therapy for post-menopausal osteoporosis and corticosteroid-induced osteoporosis. In Europe, an additional filing has been made for Paget's disease. Phase III clinical trials of risedronic acid are in progress in Japan and Australia in patients with osteoporosis.The Japanese launch of risedronic acid is expected during 1999. Ajinomoto has licensed risedronic acid from Procter and Gamble for development and marketing in Japan, and Ajinomoto also has a codevelopment agreement with Takeda for risedronic acid through a sublicensing agreement. Risedronic acid is also licensed to Hoechst Marion Roussel in Japan.Procter and Gamble claims that risedronic acid has the advantages of lower dosage levels and fewer adverse effects compared with Merck's alendronic acid product (Fosamax®) for osteoporosis. The mechanism of action of bisphosphonates in reducing bone resorption is unknown at present. It is possible that they may reduce osteoclast activity directly, or induce the production of an osteoclastinhibiting factor by osteoblasts.Risedronic acid is a calcium metabolism regulator so it may also be useful in patients with hyperparathyroidism, malignant hypercalcaemia, osteolytic bone metastases or other bone diseases. In addition, a recent study has shown risedronic acid to significantly reduce the incidence and size of bone metastases in anin vivomodel of breast cancer.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;S 12911 is a divalent strontium salt. In low doses, strontium salts stimulate bone formation and inhibit bone resorption.[1] S 12911 is in phase III clinical trials in France with Servier as a potential osteoporosis therapy.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Teriparatide [hPTH 1-34, LY 333334, MN 10T, parathyroid hormone (1-34), parathyroid hormone (1-34) - Asahi, parathyroid hormone (1-34) - Eli Lilly, parathyroid hormone (1-34) - Rhône-Poulenc Rorer, teriparatide acetate] is a synthetic polypeptide which consists of a 34 amino-acid fragment comprising the biologically active N-terminal portion of human parathyroid hormone. The drug was originated by Armour Pharmaceuticals (Rhône-Poulenc Rorer) in the US and the acetate was subsequently launched in the same country as Parathar®, a formulation for intravenous infusion. Parathar® is used for the differential diagnosis of hypoparathyroidism and pseudohypoparathyroidism. Teriparatide is licensed to Asahi Chemical in Japan and is undergoing phase II clinical trials there as a once-weekly, SC injection for the treatment of osteoporosis. Eli Lilly is conducting global phase III trials of teriparatide for the treatment of osteoporosis, including a large, multicentre, randomised trial. This use of the drug is based on its bone formation stimulating properties. Preclinical studies indicate that a combination of teriparatide with a bisphosphonate such as risedronic acid may be a particularly promising approach for the treatment of osteoporosis.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Tibolone (KB 889, ORG OD 14, ORG OD14, Livial®, Livifem®, Boltin®) is a synthetic steroid which is indicated for hormone deficiency and osteoporosis. It has estrogenic and progestogenic properties, and is weakly androgenic. Tibolone is being developed with Organon and Nourypharma (both subsidiaries of Akzo Nobel) and is licensed to Kanebo in Japan. Donmed is developing the drug in South Africa. Tibolone is launched as a hormonal replacement therapy for the treatment of menopausal disorders in Italy, the Netherlands, the UK and Brazil as Livial®, in South Africa as Livifem® and in Spain as Boltin®. The drug is in phase III clinical trials in Europe, the US and Japan as Livial® for the treatment of osteoporosis.Tibolone is also undergoing preclinical development with Organon in the Netherlands and France for the potential treatment of breast cancer. Tibolone also has anti-ischaemic properties similar to estrogen and may have potential in the prevention of primary and secondary coronary artery disease.Tibolone appears to be an effective agent for the treatment of osteoporosis although care is needed regarding contraindications and potential drug interactions.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Trimegestone (RU 27987) is a progestogen which lacks androgenic activity. In Europe, it is in phase III clinical trials as an oral formulation and phase I trials as a patch formulation for the treatment of menopausal symptoms, including osteoporosis. Phase I trials in this indication are also in progress in Japan. In addition, its efficacy in treating menstruation disorders is being assessed at the phase I level in France and Japan. Hoechst Marion Roussel is developing the compound in collaboration with Wyeth-Ayerst (American Home Products). Trials are in phase III in the US. It is anticipated that trimegestone will be approved for marketing as both a tablet formulation and as a patch formulation in 1999.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS