Last week we spent some time discussing the shortcomings of the generic vs. brand name drug debate, focusing on an example of non-bioequivalence between the antidepressant Wellbutrin XL and its generic competitors.
Three days later, I then received an e-mail from one John Procter about a movement to get Washington to move forward on the approval of lower-priced generic biotechnology drugs now that original branded products are facing patent expiration. One source indicates that a $20 billion market value of biological products will be coming off patent by 2015. The US FDA has been reluctant to approve general formulations of biological agents that include protein hormones like erythropoietin and other protein-based therapeutics such as antibodies or antibody-toxin/radionuclide conjugates.
A virtual monopoly has limited access to biotechnology drugs for too long, costing our families billions at a time when healthcare costs continue to rise. Recent studies show Americans could save $378 billion over 20 years if generic biologics-costly drugs made by manipulating proteins-were available in the United States as they are in Europe. Although biologics are more than 20 times more expensive than traditional drugs, Washington has yet to approve generic versions in the U.S.
It is time for Washington to give us a choice of generic biotech drugs to treat diseases such as diabetes, cancer, and Alzheimer’s.
We need your help!
Watch our YouTube video [or see below the fold] to Congress, and post your own video or message to lawmakers on why access to safe, affordable biotechnology drugs should happen now!
The e-mail links to this YouTube video featuring “Mike” a scientist at the Boulder, CO, biotech company, Insmed. Insmed is attempting to gain approval for their own generic forms (“follow-on” products) of protein therapeutics. Ed Silverman at Pharmalot also blogged about Mike last month.
Many readers who work(ed) in labs have experience with producing recombinant proteins in E. coli, various yeast species, insect cells, or mammalian cell hosts. You can produce a bungload of protein with very small fermenters or culture systems, which might make the average Joe Scientist think that there should be no issues with approving generic protein biologics.
However, I have produced many insoluble proteins that although resolubilized, lack biologic activity and are, therefore, useless. (Although a pharmacologist, I’ve actually done some circular dichroism spectroscopy to examine protein structure). In other cases, one must engineer their protein expression clones for codon optimization in the host of interest. Protein therapeutics are also often modified post-purification with polymers like polyethylene glycol to minimize their immunogenicity and/or improve plasma half-life. Producing biologically active proteins can also depends upon protein can be freeze-dried and reconstituted properly and maintaining its biologic activity.
An example of a very promising anti-cancer protein therapeutic called TRAIL is still experiencing difficulty in gaining initial approval because protein made in one expression system is terrifically toxic to the liver – expressing the protein in the presence of zinc seems to promote the proper, non-hepatotoxic conformation, the the trail to approval for this agent has been quite bumpy (pun intended – nice Hepatology PDF overview).
I am certain there are experts among our readers who have firsthand experience with innovator and follow-on protein therapeutics. In addition, we are fortunate to have readers in Europe, Australia, and other countries where follow-on protein therapeutics have been approved.
My question is this: Is the reticence of US approval for follow-on biologics based on politics, business, actual scientific challenges in producing biosimilar protein therapeutics, or a combination of the three?