BMS recently withdrew its US FDA application for the hepatitis C drug, asunaprevir. It is probably a very wise decision on BMS’ part, because asunaprevir is close in formulation and results to several other generation 2 NS3 protease inhibitors*. Instead, BMS seems to be focusing on its more unique product, the NS5A replication complex inhibitor, daclatasvir, of which they say in their Oct. 7 press release, is “currently being investigated globally in multiple treatment regimens for HCV patients with high unmet need…we believe that daclatasvir-based regimens have the potential to fill continued unmet medical need in the U.S. and elsewhere in the world.”

HepCBC has recently been advocating “Stand Alone” drugs, which doctors will be free to mix and match according to the unique needs of each patient, quickly adapting their changing HCV treatment “cocktails” in response to the most recent results of rapidly-evolving international research. We want patients to have easy access to combinations such as sofosbuvir+simeprevir (Gilead’s plus Janssen’s drugs), or sofosbuvir+daclatasvir (Gilead’s plus BMS’ drugs). That is why we supported the “un-bundling” of ribavirin from interferon, now known as IBAVYR (tradename for Pendopharm’s ribavirin). More about Stand-Alone drugs from an article in our September issue of hepc.bull (p.3):

“Single-Company” vs. “Multi-Company” Cocktails

“Sofosbuvir in combination with several other drugs in an interferon-free combo is ‘in the pipeline.’  The sofosbuvir/ledipasvir combo is the first of these combos to reach Health Canada. However, a ‘two-company combo’ of sofosbuvir/simeprevir is currently being used extensively in the USA (simeprevir – trade name GALEXOS – is a Janssen drug already approved in Canada in a combo with interferon and ribavirin). Another ‘two-company combo’ of sofosbuvir/daclatasvir was approved August 27, 2014 by the European Commission (daclatasvir [trade name Daklinza] is a Bristol-Myers Squibb drug).

Like most businesses, Gilead prefers that their products are combined with other products from their own company. Following in Gilead’s footsteps, other pharmaceuticals are also seeking to put together an interferon-free combo which contains only their company’s products; these include AbbVie, Merck, and Bristol-Myers Squibb. See: http://natap.org/2014/EASL/EASL_86.htm. Significant litigation and patent challenges also seem like an avoidable waste of time and money that could be better spent on R & D. See: http://www.firstwordpharma.com/node/1225537#axzz3BSXPuPyt .

This ugly side of HCV drug competition might not exist if we could get rid of the emphasis on a single company alone achieving the Holy Grail of HCV treatment: a single-dose, all-oral, pan-genotypic cure without side-effects. Some have suggested the use of ‘Patent Pools’ to spread R&D risk and foster more cooperation among pharmaceutical companies; this is an avenue deserving exploration for future HCV drug development, perhaps even right here in Canada.

We here at HepCBC wonder if there might be some time, cost, and public health benefit in regulatory bodies (at all levels) separately approving each component of a combo on a stand-alone basis, rather than approving each of these (rather numerous!) upcoming single and multi-company combos as each comes along. For example, Canada recently did this for a stand-alone version of ribavirin, trade name IBAVYR, through ‘un-bundling’ it from interferon.

Significant R&D money has gone into essentially parallel development of very similar ‘ingredients for the HCV Cocktail’ simply to create a slightly different proprietary formula. Likewise, significant government (taxpayer!) time and money is spent approving not only each ingredient, but each combination of ingredients. This could lead to far better choices for Canadian patients and their physicians, as well as fostering a more cooperative research & development environment. It would seem that HCV Treatment Guidelines which already are formulated and updated regularly by the Canadian Assn. for the Study of the Liver, could serve to guide doctors as they try to find the best treatment ‘Cocktail’ for each unique patient’s condition – and financial situation.”

Complicating this in Canada is our federal drug-review process which now seems to mostly look at one-company combos, and the individual provinces’ Pharmacare review processes (required in order for patients to be reimbursed for the cost of the drugs) which must now approve each hepatitis C treatment combo separately, rather than each component of the cocktail. We really are hoping that the governments will take a fresh look at the hepatitis C drug approval process.

READ MORE from BMS Oct. 7, 2014 press release: http://news.bms.com/press-release/rd-news/bristol-myers-squibb-statement-about-asunaprevir-us&t=635482740339913288
* specifically, linear and macrocyclic noncovalent inhibitors of the NS3-4A enzyme