So I wrote this article for Seeking Alpha but they are busting my chops, that I need 4-6 other articles until they will publish anything, I figuire that I might as well post it here for everyone elses benefit because I don't plan on writing 4-6 other articles by the time there PDUFA date rolls around:
What Problem is Addressed
• EXPAREL is a long acting anesthic/analgesic targeted at post surgical pain management and is comprised of bupivacaine encapsulated in their proprietary DepoFoam technology. Bupivacaine is an FDA approved anesthic/analgesic used in pain management for over 20 years but only provides relief for approximately 7 hours. Since the suture is closed after the surgery, re-administration after those 7 hours is typically not an option, and the patient is usually switched to an opiod. This switch to an opiod, while cheaper on a per dosage basis, can lead to higher costs to the hospitals and providers due to the side effects and longer patient monitoring associated with opiod use. By using their DepoFoam technology, Pacira has encapsulated bupivacaine in a structure comparable to a bubble bath which releases the dosing over a 72 hour period. This results in a reduced level of opiod administration to deal with patient’s post operative pain. The key here is that both bupivacaine and the DepoFoam technology (in two other products) have been FDA approved prior to EXPAREL.
What are the Risks
• The issue of Chondrolysis – Chondrolysis is a debilitating condition where the cartilage in the shoulder or knee essentially dissolves, and you are left with bone rubbing on bone and extreme pain. Patients were going in for shoulder or knee surgery and since bupivacaine on its own lasts for only 7 hours, some doctors were installing pain pumps that bathed the joints in bupivacaine dissolved in water over extended periods of time. This method of bupivacaine administration has since been proven to eat away at the cartilage in those joints leading to Chondrolysis. Where EXPERAL differs is that it is injected into the tissue and not through intra-articular administration along with the fact that it is a one time injection which slowly releases bupivacaine over 72 hours.
• Bupivacaine in high doses can cause cardiac arrest – Given how focused the FDA has been on the issue of drug implications on the heart, it is reaffirming to hear that Pacira has conducted two thorough QTc studies that did not cause significant QTc prolongation even at the highest doses administered. This can be attributed to the long-term slow release of bupivacaine through the DepoFoam technology compared to an injection of bupivacaine on its own.
• “Cold-Chain Distribution” required – This will be more expensive and will render the drug ineffective if the temperature of the solution exceeds a certain temperature. They have already worked with partners in regards to this with their two other FDA approved drugs that are based on the DepoFoam technology.
• Will their Phase 3 study focusing on post surgical treatment of patients that underwent a hemorrhoidectomy and bunionectomy be enough to give them the broad label they are seeking to treat all types of post surgical pain –The initial labeling might have some limitations surrounding administration to joints, but overall the study provided enough data to make a decision in regards to most post surgical applications.
Who believes in the story – with their wallets.
• HBM BioVentures, MPM Capital, OrbiMed Advisors and Sanderling Ventures combined owned approximately 96% of the outstanding stock prior to the IPO and a combined 10,962,096 shares. It is reassuring to see that the combined share count of these four initial investors actually increased to 12,033,524 shares after the IPO in comparison to them selling off once a market was made for their shares.
I think come July, there is a very good chance that a FDA approval will be awaiting the team at Pacira Pharmaceuticals.
How can you call this "actual due diligence"?
You only state a few points about this drug, not clear how this helps any readers, jumping in on a focused area in the middle of the development from a historical perspective.
This is like giving a drug as a "bubble bath" formulation? Micelles are what you are describing, not liposomes. Come on, man. What bubble bath lasts for 72 hours? Can see why they would not want to publish this. You need to bone up on your knowledge of pharmaceutical formulations and pharmacokinetics.
You are a ways off on your analysis and telling the whole story to make sense to first time readers. Sounds like you are short the way this is written, picking out some negatives and calling this a "bubble bath."
I will agree with you that my post should not be labeled "actual due diligence" I did not step foot in any manufacturing facility or see any of the trials first hand... What I should have titled it is "my opinion on why EXPAREL will be approved"
In regards to your criticism of my use of the simile "bubble bath" , you forgot to include the remainder of my text "that releases over a 72 hour period". I could have also included that the structure breaks down in a highly precise and uniform matter but Merely just trying to make an easy visual of what type of structure is encapsulating the active drug. Might be crude but in my opinion gets the point across.
Further I would appreciate a little more feedback on how you think this analysis is "ways off"
Thank you, happy Easter.