Drug In Focus December 2011

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Drug In Focus: Ibandronic Acid

The following data is extracted from GenericsWeb Pipeline Patent Intelligence and is intended to give a brief outline of factors affecting the potential launch of generic equivalents of Roche and GlaxoSmithKline’s top-selling bisphosphonate Ibandronic Acid. Ibandronic Acid products had reported global sales of CHF 1bn in 2010.

General information

Ibandronic Acid is currently available as film coated oral tablet and solution for intravenous injection formulations. Currently, the Bonviva®/Boniva® monthly 150mg oral tablet and the Bonviva®/Boniva® quarterly 1mg/mL intravenous injection formulations of Ibandronic Acid are indicated for the treatment of postmenopausal osteoporosis. In some countries outside of the US Bondronat® formulations of Ibandronic Acid (available in 50mg tablet and 2/6mg infusion concentrate) are indicated for the prevention of skeletal events in patients with breast cancer and bone metastases, and the treatment of tumour-induced hypercalcaemia.

Figure 1: General Information table for Ibandronic Acid

INN Constraint Comment

Patent protection for the Ibandronic Acid molecule extends to June 2011 in several European states and to July 2012 and March 2012 in Australia and the USA respectively.

Patent families DE4228552A, DE19615812A and EP98119102A relate to specific marketed formulations of the Oral tablet and Injectable solution respectively. Patents in these families are generally not considered to be a constraint to generic competition against the currently marketed injectable formulation because the protected technology is likely to be circumvented by re-formulation of generic equivalents. However, application EP1658852 seeks to protect any instant-release oral film coated dosage form of Ibandronate and should be monitored carefully by those companies wishing to launch such a dosage form upon molecule patent expiry.

A fifth patent family EP02010136A with expiries of May 2023, generally protects the use of Ibandronic Acid in the treatment of osteoporosis by monthly oral administration of a single dose of 150mg of Ibandronic Acid. Patents within the family are generally constraining for the Boniva 150 mg dosage form and its osteoporosis indication. Opposition proceedings against European patent, EP1506041, were brought by several generic companies, the proceedings of which are on-going. US equivalents in this family have also been challenged through the courts with little success. Since the 150mg oral tablet only carries the Osteoporosis indication, patents in this family will block generic competition for this dosage form until May 2023 unless successfully challenged. 2.5mg and 50mg tablet strengths are generally not constrained by this patent family, so may face competition where a generic approval route is available.

Figure 2: Key Patent Indicator; the most significant patents protecting products containing Ibandronic Acid
Figure 3: Patent Family View priority application DE3623397A

Figure 4: Marketing Authorisations for products containing Ibandronic Acid in Key Countries

In the UK and EU, a variety of generic marketing authorisations relate to all dosage forms and strengths, however some of these are unlikely to be commercialised until the relevant patents expire or have been revoked.

Figure 5: US Tentative FDA Approvals for Generic Ibandronate Sodium

Amongst the US approvals, tentative FDA approvals have been identified for Ibandronate Sodium. Following Paragraph IV filings for generic Boniva, extensive patent litigation has been identified between Roche and Actavis, Apotex, Cobalt/Watson, Dr Reddy’s, Genpharm, Mutual, Orchid and Teva.

Figure 6: Top Patent Applicants

This graph shows a representation of patentees who have filed the most patent families for this INN. Note the prominence of relevant applications filed by manufacturers of competing bisphosphonates, Merck (Alendronic Acid), Novartis (Zoledronic Acid) and Procter & Gamble (Risedronic Acid); and the prominence of generic player Teva as well as the diversity of applicants represented by the significant portion outside the top five.

Figure 7: Patent Filing Trend

Represents the timing of the earliest priority filing date for each patent family identified for this molecule as well as the type of claims found in the applications. Note the regular filing of patent applications in the area of process, particularly in the complete synthesis of Ibandronic Acid, formulation and use patents since the initial European approval of Bondronat in June 1996 and the later approval of Bonviva in September 2005.

Figure 8: Patent Category Distribution

The types, number and relative distribution of patents that have been filed for Ibandronic Acid obtained via a comprehensive patent search (Pipeline Developer report). Note the dominance of formulation patent families which cover other administration-specific compositions in addition to the currently available oral tablet and injectable formulations, and the prominence of use patent families which relate to a wide range of bone-related conditions. Several combination patent families identified specifically relate to formulations comprising bisphosphonates in combination with vitamin D compounds.

In summary, molecule protection remains for the Ibandronic Acid molecule in certain major territories, but this is set to expire in the next 12 months. Evidence of potential generic Ibandronic Acid competitors can be seen via marketing authorisations, however Roche have protected their 150mg oral dosage form well by patenting its use for osteoporosis, thus preventing a variety of generic competitors from launching an equivalent to what is likely to be their biggest selling dosage form until 2023. It is possible that some erosion of sales from this dosage form will be experienced as generic competitors launch 50mg dosage forms upon molecule patent expiry, these generic versions being prescribed or dispensed instead of the brand 150mg product where legal.

Considering the vast global sales of bisphosphonates, generic manufacturers will undoubtedly be closely watching the patent landscape surrounding Ibandronic Acid, the outcome of its on-going litigation and opposition, and any future developments in its lifecycle.

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December 2011
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