I ask the forum whether the company knew about, or ought to have known about, problems with the patches back in October 2013. For example, was there any skin irritation back in October 2013? Has anyone on this forum been able to explain this silence about patch issues satisfactorily? Has the company?
Henriette, it’s only my guess, but I think that what you may have interpreted as “problems with the patches” may not have been interpreted the same way by others.
I assume you are referring to the following section of the CEO’s Report in the Annual Report
Three key success criteria from the perspective of the FDA and commercial partners will be tested during 2015:: (i) TPM®’s ability to overcome oxymorphone’s potential to cause dermal irritation and sensitisation, (ii) the wearability and durability of the newly formulated patch design, and (iii) initial evidence that the TPM-OM patch as designed is appropriate to provide chronic pain sufferers with adequate drug levels to reduce pain.
Perhaps what you view as indicating “problems” or “issues” with the patches, others have simply interpreted as indicating that further data is required (and was always going to be required).
To your question of whether any skin irritation was reported back in October 2013, the company did report that “the patch was well tolerated by subjects with minimal irritation” in both their webcast of April 2014 and in the Abstract presented by Dr Paul Gavin at the American Pain Society 33rd Annual Scientific Meeting on 1 May 2014. (1)
You also ask if the company should have known about potential problems back in 2013. I take this to refer to the potential for skin irritation from an oxymorphone patch. The answer is yes. Potential for skin irritation is always an issue with transdermal patch products and will always have to be assessed during development. Potential for irritation can come from any component of the patch, including the transdermal system itself, the adhesive used and the API. You will note that all three oxymorphone patch PK studies held to date included an assessment of tolerability, with frequency of skin irritation at site being one of the determinants. (2)
Is the API itself (oxymorphone) known to potentially cause skin irritation? The answer appears to be yes, all opioids potentially can. If you check MSDS sheets for different opioids, you will see skin irritation is listed as a potential side effect/hazard.
Has the company suggested before this Annual Report, and prior to people investing since October 2013, that skin irritation and sensitisation could be a potential issue with development of an oxymorphone patch? Yes, when the oxymorphone patch was first announced on 03/12/12, and again when the first single dose oxymorphone patch trial results were announced on 25/03/13, the company stated some of the issues that would need to be addressed during development
Any patch delivery technology needs to consider issues including skin irritation, adhesion (especially in warm climates), efficacy, abuse potential, sensitisation, patch application location and size.
Have these studies detailed in the Annual Report ensued as a result of POH meeting with the FDA? No. My advice from the company was that these studies are the result of internal regulatory advice in conjunction with external consultants.
Do existing transdermal opioid patches have the potential to cause skin irritation or sensitisation? Yes. If you check the listed potential side effects of existing transdermal opioid patches you’ll find skin irritation listed. Also, you might like to check the following two studies, which are specifically related to skin irritation caused by transdermal opioid patches. (3,4)
Has anyone on this forum been able to explain this silence about patch issues satisfactorily?
Reading between the lines, I think you may be referring to the interminable delay in the oxymorphone patch program, which you seem to be relating to the studies which are referred to above. Obviously, it’s always best to ask the company directly, rather than rely on what is posted on Hot Copper. What I do know is that the Annual Report clearly points to tech transfer as having been a source of major delays. This corresponds both with statements in the November newsletter and with feedback I have received in communications with the company. Are delays common during tech transfer? Yes – if you google tech transfer in pharmaceuticals you can read about some of the common causes of delay. Of course, that doesn’t necessarily mean that all delays during tech transfer are excusable.
Henriette, I don’t know if this properly addresses your questions but it’s the best I can do. If you want to know anything more it would obviously need to come from the company. The only other thing I can add is that I have recently emailed the company to let them know that frustrated shareholders are seeking more communication on a range of issues. I suspect that I’m not the only shareholder to have done so! I believe that this message has been heard loud and clear and I do think that the company will respond. Just don't ask me when!
- http://www.jpain.org/article/S1526-5900(14)00378-2/fulltext
- http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=transdermal oxymorphone&ddlSearch=Registered
- http://www.ncbi.nlm.nih.gov/pubmed/16574034
- http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0536.2008.01472.x/abstract
(20min delay)