Global Insight Perspective | |
Significance | The FDA has dealt a surprising blow to Momenta and its co-development partner Sandoz (part of Swiss firm Novartis) by refusing to approve M-Enoxaparin, a generic copy of Lovenox. |
Implications | Lovenox is a complex drug but a chemical drug. This means approval of a copy is subject to rules applicable to generics, and the co-developers have been able to file under the abbreviated approval procedure. |
Outlook | The FDA's rejected the drug on grounds of insufficient immunogenicity data. This demonstrates the agency's determination to treat complex generics in the same manner as it plans to treat biosimilars, by requiring more clinical data than for simple generics. The rejection casts doubts about the feasibility of Momenta's entire drug characterisation and development approach, but these are doubts are unfounded in our view. |
FDA Deals Momentous Blow to Momenta
For the past few years we have considered small U.S. biotech company Momenta to present the single most potent risk to Sanofi-Aventis's pipeline, as the company's polysaccharides technology has allowed it to develop a much fuller characterisation of the complex Lovenox compound. The drug is made up of a complex chain of low-weight heparins. Its individual components are small molecules, but the way these molecules are connected is so complex that Sanofi-Aventis itself claimed it could only characterise 80% of the chain. The French company claimed this made Lovenox's complexity akin to that of large biotech drugs, and thus argued the principles applied to a copy version's approval should be similar to those used for biotech drugs.
Momenta begged to differ. With its proprietary technology, the company said it was able to characterise the Lovenox chain to a greater extent than its developer. Having engineered a compound mimicking the originator drug as closely as possible, Momenta secured a large co-development and marketing partner in Novartis and proceeded to seek U.S. regulatory approval for its copycat version.
Yesterday the company said Sandoz had received an FDA non-approvable letter for M-Enoxaparin. The grounds for rejection, according to Momenta's statement, are that "the application does not adequately address the potential for immunogenicity of the drug". Momenta's shares promptly lost 58% of their value despite assurances that the company and its partner believe they had the data "to address what [they] anticipate to be the FDA's concerns".
Outlook and Implications
The rejection of M-Enoxaparin is a rare outcome for an abbreviated New Drug Application (ANDA)—the type of application filed for approval of generic copies of chemical drugs. There is no abbreviated approval procedure for copies of complex biotech drugs in the United States. However, even if there were one Momenta and Sandoz would have still been entitled to file an ANDA, considering that the originator product is not strictly speaking a biologic and was approved as a chemical drug.
The FDA rejection clearly demonstrates that the agency is prepared to apply stricter approval criteria for complex chemical drugs, and that it is the complexity of the compound and not whether the drug is chemical or biologic that determines the criteria for review. Notably, the rejection is based on a lack of immunogenicity data. Immunogenicity (i.e., the risk of causing an immune reaction in the body) is typically the main concern for approval of biotech drugs. While it is true that Lovenox is derived from pig tissues and could potentially carry a higher risk, in this particular case the FDA may be positioning itself to set the approval bar higher for generic copies of complex chemical drugs. If this is so, how high is the bar going to be for approval of biosimilar copies of biotech drugs?
The market's reaction has been to doubt the soundness of Momenta's technology, and shareholders are questioning Momenta's approach of characterising complex drugs before engineering copycat versions. Our view on the value of the technology has not changed as a result of the FDA rejection. Global Insight viewed Momenta as a huge threat to Sanofi-Aventis in 2005—before the M-Enoxaparin approval application was filed—and we still retain this view as the technology is sound. On top of that, Momenta has a powerful co-development partner on its side that has experience of fighting the FDA in court to secure approval for a biosimilar product. There is a high chance that Momenta and Sandoz have the additional immunogenicity data the FDA seeks and could secure approval as early as next year. The main Lovenox patent ('618) was invalidated in the United States earlier this year, but the product is protected by a reissued version of the same patent (also valid until 2012). It may be possible for Momenta to circumvent the reissued patent and launch a generic competitor to Lovenox before the 2012 patent expiry date. Sanofi's blockbuster had sales of US$2.8 billion sales in the first nine months of this year.
Related Articles
- United States: 29 June 2007: Momenta Faces Lovenox Copy Approval Delay
- France: 9 February 2007: Sanofi-Aventis Loses Lovenox Patent Suit in California, Faces Plavix Recall in France
- France: 13 April 2006: Reversal of Lovenox Patent Ruling Positive for Sanofi, but Other U.S. Dangers Loom
- Global: 12 April 2006: Teva and Amphastar Suffer Setback in Lovenox Patent Battle
- France: 31 August 2005: Sanofi-Aventis Exceeds Expectations in H1 Results, as Momenta Threat Grows
- Global: 19 August 2005: Momentous Threat in Store for Lovenox, as Momenta Prepares to File ANDA
- France: 17 June 2005: Sanofi-Aventis Loses California Court Battle, but Expected to Win the War as USPTO Reissues Original Lovenox Patent