GS identifies strong 2005 osteoporosis pipeline

Current treatments for osteoporosis consist of oestrogens, calcium, and vitamin D, in addition to new types of treatment. Of these new types, the bisphosphonates have become one of the most successful modern treatments, expanding from launch 1995 to 33 million prescriptions in 2004.

Bisphosphonates are non-hormonal agents that have reshaped the osteoporosis market. These compounds actually decrease both bone resorption and formation. Bisphosphonates bind to forming bone crystals, and directly inhibit osteoclasts.

This shifts the equilibrium in favour of formation, and leads to a higher bone mineral density for patients. The most common side effects form bisphosphonates are upper gastrointestinal symptoms, such as esophagitis and heartburn owing to irritation from the pills.

According to investment analysts Goldman Sachs (GS)​, Bisphosphonate growth has been relatively stable recently with a 10 per cent growth in 2004 and 10 per cent Merck's Fosamax and Proctor & Gamble/Sanofi-Aventis' Actonel, have mainly competed on convenience, moving from daily to weekly dosing.

Currently, the weekly formulation of Fosamax is the top selling prescription bisphosphnate, with 60 per cent share of new bisphophanate prescriptions as of March 2005. Merck's strategy appears to be to show the better efficacy of Fosamax compared to competitors.

In March this year, the Food and Drug Administration (FDA) approved Roche/GlaxoSmithKline's Boniva for once-monthly dosage, signifying a potential threat to the existing competition. Efforts to extend the duration of effect continue, as Roche seeks quarterly dosing for Boniva and Novartis explores yearly dosing for Zometa.

GS's new report, which focuses on the pipeline of new treatments for Osteoporosis, identifies Boniva to have estimated peak sales of $830 million after an anticipated launch date of April 18, 2005. The drug obtained FDA approval in 2003 for once-daily dosing, but launch was held back until a longer-lasting, less frequent dosing regimen was also available. Boniva once monthly was approved on March 25, 2005.

Novartis's Aclasta, with its peak-estimated sales of Zometa/Aclasta of $2.97 billion has an expected launch date of 2008. Novartis is attempting to market the first bisphophanate to be administered yearly, as an injection. The active ingredient is the same as Novartis's Zometa, currently indicated for bone metastases and hypercalcemia of malignancy. Novartis is expected to file its new drug application (NDA) for Aclasta in early 2007.

The report identifies a number of new emerging classes of drug that are used to treat osteoporosis, both alone and in combination with one another. All of the treatments stimulate receptors on the osteoclasts, altering the equilbrium in favour of bone remodelling.

Hormone replacement therapy (HRT) has had the long-standing benefit of preventing bone loss in post-menopausal patients. With rising concerns of increased cancer risk with oestrogens, new selective oestrogen receptor modulators (SERMs) have been shown to have similar efficacy while not stimulating receptors in the breast or uterus, reducing risk of cancer.

Data from trials involving Pfizer's Oporia (lasofoxifene), with estimated peak sales of $500 million and an expected launch in 2005, suggest that these second-generation SERMs may be more potent than Eli Lilly's Evista in terms of increasing bone mass density and lowering LDL cholesterol.

Wyeth's bazedoxifene, with a launch date proposed for 2006, is an SERM hoping to capitalise on the success of Lilly's Evista. GS thinks that Wyeth's main selling point will be the differentiation against the key side effect for Evista, namely the hot flashes. Other drugs have failed because of endometrial proliferation, a hurdle that Wyeth's drug will have to face as well.

Designed to be analogous to naturally occurring parathyroid hormones, NPS Pharmaceuticals' Preos has a launch date of 2006. Also a recombinant parathyroid hormone product, Preo's clinical data demonstrated improvement in women with mild to moderate osteoporosis. In rat studies, no tumours were detected at low doses. GS expect NPS to emphasise the "no effect dose" of Preos although they suspect the FDA may still view tumorgenicity as a class effect and require the same black box warning for Preos as for Forteo.

RANK monoclonal antibodies are a new therapy that inhibits the receptor activator of nuclear factor Kappa B (RANK) ligand, an important pathway in the metabolism and life cycle of osteoclasts. The antibody itself is similar to osteoprotegerin, a naturally occurring protein that controls RANK ligand activity in the cells.

Amgen's AMG162, with an expected launch date of 2007-2008 has been shown to be as effective as weekly Fosamax in decreasing bone loss. The effect of AMG-162 seems to be reversible, and it may have more synergistic effects in combination with other drugs, such as parathyroid hormones. In addition, AMG 162 has had fewer upper gastrointestinal side effects than Fosamax did. AMG 162 phase III trials started in the third and forth quarters of 2004.

Osteoporosis is estimated to affect 20-28 million people in the United States. It is most commonly found in elderly, post-menopausal women, and associated with an increased risk of hip and vertebral fractures. Oral corticosteroid use also can be associated with osteoporosis. Recent reports calculate that annually, more than 300, 000 hospital admissions are due to hip fractures from osteoporosis in women, as are more than $9 billion in direct medical costs. The disease is characterised by progressive bone density loss.

Readjusting the balance between bone loss and bone formation not only explains how osteoporosis occurs, but also provides the opportunity for new treatment regimens and products for this disease.

Bone is a constantly changing tissue of the body, adapting to changes in the body's internal (i.e, hormones) and external (i.e. external stresses) environments. Bone is also always in a homeostatic state between breaking down (bone resorption) and then building up again (bone formation). This equilibrium typically shifts during aging, with a higher ratio of bone growth compared to bone resorption until age 25, and then a lower ratio after 45. This is the reason bone mass tends to be higher in children and young adults, and lower in the elderly.