Looking for opportunities in the Merck respiratory portfolio

Looking for opportunities in the Merck respiratory portfolio

March 07, 2016

On 26 February 2016, Merck published its 2015 annual results. This gives us the annual excuse to update our records on what Gx opportunities might lie ahead.

Over the years, Merck has pursued a varied and successful respiratory portfolio centered around Mometasone. It managed to market pMDis, DPis and nasal sprays:
     Dulera pMDi (monetasone+formoterol)
     Proventil pMDi (albuterol)
     Asmanex Twisthaler (monetasone)
     Nasonex nasal spray (mometasone)
This portfolio (excluding solid dosage forms used in the treatment of respiratory diseases e.g. Singulair etc.) grossed in excess of $ 1.7 billion in 2015. This portfolio is curiously unchallenged by generic competition in the US, and only partially in Europe, mostly by Gx Nasonex products.

A summary of Merck sales figures
Merck reported some of the its sales figures in its 2015 annual financial statement:
                 Nasonex – USD 858 Million
                 Dulera – USD 536 Million

No figures are reported for Proventil nor Asmanex this year, which could be because those sales are lower than USD 200 Million (the financial statement seems to give details of high grossing products only). In 2014 Proventil achieved USD 219 M, while the last figure for Asmanex dates back to 2012 with USD185 Million.

Here is a summary of the worldwide sales figures over the last 9 years (in '000,000 USD):

Year  Nasonex  Dulera  Proventil  Asmanex
2006 944     103
2007 1,092     162
2008 1,155     180
2009 1,056   26  
2010 1,219 8 210 208
2011 1,286 96 155 206
2012 1,268 207 157 185
2013 1,335 324 190  
2014 1,099 460 219  
2015 858 536    

The overall picture for the Merck portfolio is one of declining sales, in particular for Nasonex, hit by both generic competition in Europe and price reductions due to austerity measures. Nasonex reached its peak sales in 2013, Dulera is still rising, Proventil will soon plateau, and Asmanex is on the decline.

Opportunities for Gx products
The sales decline of the Merck portfolio is only bad news for Merck. At USD 858 millions a year, Nasonex is still a good Gx target, so is Dulera.

The case for Proventil is more difficult to make as other competitors and Gx suppliers already have albuterol pMDI alternatives.

Making a Gx of Asmanex is still possible, but would need to be carefully considered. The Twisthaler is not an easy device to replicate, it may cost up to USD 20 Million inclusive of a device manufacturing line for human use. The added complication of needing in vivo clinical trials likely to cost in excess of USD 15 Million, does not make a 505j ANDA the cheapest route. A 505b2 filing might be wiser, as long as an off-the-shelf device is sourced and robust commercialisation strategy is in place.

What’s going on with Nasonex?
In the EU, Nasonex is more or less fully genericised.

In the US, there are still no generics of Nasonex. Nasonex was approved on 1 Oct 1997, and the last patent is due to expire on 3 Oct 2017. Teva and Apotex both won I.P. litigation cases against the Nasonex patents and won; yet none of them have a Gx on sale. Teva conducted a clinical trial (n=800) in Jan 2012, and file an ANDA in May 2015; while Apotex filed an ANDA with a 30 month stay due to expire in May 2012, yet no Apotex Gx Nasonex is on the market.

I find this strange. What company would gain the right to sell a Gx products and not do so? Why aren’t Teva and Apotex not selling Gx of a lucrative product for which they have no legal impediments?
              First, one must not exclude the remote possibility of an agreement between Merck and potential rivals, even if it were illegal.
              Second, the dossiers provided by Teva and Apotex could well have been deficient. It is interesting to note that Apotex never carried out a clinical study on its product as listed in clinicaltrial.gov. There would have no chance of their product being deemed bioequivalent.
              Third, the Teva dossier might still be under review and we may see an approval before Oct 2017.

Teva and Apotex are not the only ones having stumbled on clinical studies. Amneal (in 2014), PH&T s.p.A. (in 2013), Sandoz (in 2012), Mylan (in 2013), Actavis (in 2013), Eurofarma laboratories (in 2012) and Perrigo (in 2012), all carried out in vivo BE studies on Nasonex, and visibly failed since none of them filed. So, at this stage, it is safe to assume at only 1 or 2 serious contenders are in the race to file a Gx Nasonex, this leaves space for others.

Nasonex is therefore still a product to be conquered. It can be done: be in touch.

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