Tuesday, July 2, 2013

Biosimilars after the EULAR 2013

EMEA's Committee for Medicinal Products for Human Use (CMHP) recommended biosimilars of infliximab by Celltrion and Hospira to be granted the same indications as Remicade®. For more on this recent information (post EULAR!) please look under links for Forbes.
I don't think that biosimilars are a panacea to reduce costs; nevertheless it's worth a try. Some biosimilars are already marketed though not in the US, Japan, Australia, or the EU.

Already approved
There are some biosimilars already approved and in use.
Biosimilars of etanercept are marketed by Shanghai CP Goujian Pharmaceutical Co. in China and Colombia, as Yisaipu (益赛普) and Etanar®.
There are two biosimilars of rituximab; Reditux® is marketed by Dr Reddy's Laboratories in Bolivia, Chile, India and Peru, Kikuzubam® is marketed by Probiomed in Bolivia, Chile, Mexico, and Peru. More information can be looked up under the link for Morton, but mind that the data on study progress has been collected more than a year ago. So the list might need to be updated.

Some more preliminary information
Boehringer works on adalimumab. Avesthagen (India) works on etanercept. Sandoz, Celltrion, and Pfizer work on rituximab.
Celltrion will name its infliximab Remsima®.
"BioXpress Therapeutics S. A. (Switzerland) is currently developing biosimilars for abatacept, adalimumab, etanercept, golimumab, infliximab, and tocilizumab." (See: A. Morton et al)

Studies presented at the EULAR 2013
Three studies on CT-P13 (infliximab biosimilar):
D. H. Yoo and colleagues presented [OP0068]: "A phase 3 randomised controlled trial to compare CT-P13 with infliximab in patients with active rheumatoid arthritis: 54 week results from the PLANETRA study." Conclusions: "CT-P13 showed comparable efficacy and PKs to those of INX up to week 54. CT-P13 was well tolerated with a safety profile comparable to that of INX up to week 54."

D. H. Yoo and colleagues presented a secon study [FRI0164]: "Local tuberculosis incidence affects the rate of positive conversion in the Quantiferon®-TB gold test among patients receiving infliximab or CT-P13 therapy." Conclusions: "To reduce TB incidence in patients treated with anti-TNF agents, serial testing using QTF in the first year of anti-TNF treatment could be helpful in detecting LTBI patients who had a false negative result at baseline, especially in countries with intermediate or high incidence of TB."
Same risk profile for biosimilars!

W. Park and colleagues presented [FRI0421]: "A randomised, double-blind, parallelgroup, phase 1 study comparing the pharmacokinetics, safety and efficacy of CT-P13 and infliximab in patients with active ankylosing spondylitis: 54 week results from the PLANETAS study." Conclusions: "CT-P13 has similar PK values and a clinical efficacy comparable to INX up to week 54. CT-P13 was well tolerated with a safety profile comparable to that of INX up to 54 weeks. ADAs seem to diminish the clinical response to both agents in some patients."
Nothing unexpected.

One study on a rituximab biosimilar:
S. I. Hurst and colleagues presented [THU0104]: "Nonclinical assessments demonstrating the similarity of the proposed biosimilar PF-05280586 and rituximab." PF stands for Pfizer. Methods: "Structural similarity was determined by peptide mapping. Functional similarity was confirmed using an in vitro complement-dependent cytotoxicity (CDC) assay using Ramos cells." I don't like to go on, but in methods we're told about the necropsied cynomolgus monkeys. Let's swiftly switch to conclusions: "PF-05280586 showed structural, functional, PK, PD, and ADA similarity to rituximab-EU. Both drugs were well tolerated. The results support the development of PF-05280586 as a proposed biosimilar to rituximab."
I don't know how far Celltrion has come, but Sandoz and Teva (Israel) seem to be nearer to the goal than both Pfizer and Celltrion.

One study on Infinitam® (etanercept):
J. F. Moctezuma and colleagues presented [THU0208]: "Comparative, randomized, simple blind to evaluate efficacy and safety of Infinitam® (etanercept), associated with methotrexate compared with Enbrel® (etanercept) associated with methotrexate in patients with modeate and severe rheumatoid arthritis". Conclusions: "Clinical response, procedures and observations at the end of treatment was as expected in all group of patients. Study drug safety was similar for both drugs. All patients improved DAS28 evaluations."
It's a preliminary study!

If we put all together, there's only one biosimilar, which might make it to the market in the next 12-18 months and that's Celltrion's Remsima® (infliximab).

Forbes: http://www.forbes.com/sites/edsilverman/2013/06/28/a-landmark-for-biosimilars-eu-endorses-copies-of-a-jj-drug/  
Morton: http://www.nature.com/nrrheum/journal/v8/n7/fig_tab/nrrheum.2012.84_T1.html  


What are biosimilars good for, anyway? Someone else wants to make a profit, too. And with biologics being very expensive, biosimilars are good to make money. Could biosimilars replace biologics? I don’t think so as the pharmaceutical companies have to invest in the development and production of biosimilars. It’s my guess that the companies, who developed original biologics will stand a price fight much better as they are well past the amortisation of their investments. And biosimilars aren’t offering a new concept, they offer what we already have.

In Spain the annual cost for biologics is fixed at 9000 € (not my own research), in German we pay above 20,000 €. Why is there such a discrepancy within the EU. It means that we pay too much. Biosimilars could help to reduce this. But I doubt that there will be a breakthrough.

If Sandoz, Teva, Pfizer start developing a rituximab biosimilar, there might be more behind it than just getting a piece of the cake. I think there are other strategies involved like safeguarding against a hostile takeover.

Would I switch over patients to biosimilars? No! I would start new patients on biosimilars, however. It’s the same reasoning like I won’t switch between TNF-inhibitors, if there isn’t a reason like secondary failure or side effects. The real chance of biosimilars could only be the price.

Yisaipu (益赛普) / Etanar® and Kikuzubam® fall in the category of biomimics!


  1. I removed by chance this valuable comment, which came anonymously.
    Love you blog. What are your thoughts around the EMA ruling for the Remicade biosimilar from Celltrion/Hospira? I think it's interesting that the EMA acted so quickly with extrapolation of all Remicade's indications for Remsima.

    I wonder how MSD is going to react, especially with the refiling of Simponi IV. I was wondering what the point of the Simponi IV formulation was but i supposed it's to combat the biosimilars, similar to the strategy they tried to employ with Risperdal/Invega. Do you see Simponi IV being better for a particular patient type or as a play to combat biosimilars?

    Keep up the great work!

    1. I've deleted my reply, too. Maybe someone has copied it, so it would be nice to send it back to me.

    2. I’ve just deleted some spam from my blog and in this process also deleted the comment above, which I luckily still had as email. But I also deleted my reply. So, if you’ve read another version now, that’s the reason why. It’s better to leave than to comment anonymously. The text below is a reconstruction, a palimpsest.

      EMA‘s ruling on Remicade biosimilar from Celltrion/Hospira and extrapolation of all Remicade's indications for Remsima might stem from putting pressure on MSD to reduce costs. I doubt that this will happen.
      I would have liked to use Simponi exclusively IV, but MSD did not apply for another IV drug – that’s as far as the person from MSD has knowledge about these matters. The once a month strategy didn’t work out with the patients. At least with my patients. There some happy with long interval, but others are happy even at weekly intervals. And I have quite a lot of patients being very happy with Remicade at intervals of 15 to over 20 weeks. There might be a reason behind refiling Simponi IV, but I see more player emerging as well known drug companies endeavor on developing biosimilars.