How Titan Pharma wants to make implants the drug delivery systems of the future
What makes a technology fashionable?
Everything from music, to fashion, and even ideologies go through cycles and feed into underlying trends. In biotech, immunotherapies, CAR-T, and gene therapies have been the latest talks of the town (and in the case of gene therapy, this is round two).
But some forward-thinking ideas take a bit longer to come around the bend. And Titan Pharmaceuticals, a small California-based biopharma company, is hoping that the time is ripe for implantable devices for maintenance of chronic conditions.
BioPharma Dive sat down with Titan's President, Sunil Bhonsle, and Executive Vice President/Chief Development Officer Katherine Beebe during last week's BIO2015 conference in Philadelphia. We discussed Titan's ProNeura platform technology—an implant about the size and width of a matchstick inserted into the upper arm that's meant to provide chronic patients with a steady dose of medication—and the conditions that the company hopes to treat with its device, including opioid addiction and Parkinson's disease.
The advantages of implantable devices
Bhonsle came to Titan after a 20-year stint at Bayer, while Beebe's been with the company for eight years after working for a pharma giant by the name of SmithKline Beecham. BioPharma Dive recently reported on Probuphine, which releases buprenorphine HCl for treatment of opiate addiction through the ProNeura platform, and its promising phase III results (after an initial rejection in 2013).
Note: This interview has been edited for brevity and clarity.
BIOPHARMA DIVE: Tell me a little bit about Titan.
BHONSLE: We're focused very much on drug delivery using a platform tech that's an implant. And our goal is to take drugs, molecules that have already established a level of efficacy in an oral delivery, and then create a formulation in our implant which can provide long-term maintenance therapy. So you're looking at chronic disease settings where people are required to take medications long-term. And rather than having to take a pill every day, this is an alterantive way to take delivery of the product.
That has a couple of advantages. One is, of course, compliance. Another has to do with maintaining a very stable level of medication so you don't see a trough and peak type pattern. And each of those has benefits for the patient and the doctor.
So the first product that we chose was for treating opioid addiction, where we felt using an implant provides a number of benefits, starting with compliance. But also, it's an abuse deterrent formulation, so people aren't going to be able to sell it anywhere. That's the key part. One of the other things you read more and more about is accidents that happen with children when it comes to having things like opiates around.
BEEBE: My main responsibility has been getting this opioid addiction treatment program through development. And hopefully within the next few months we'll be able to resubmit our NDA and FDA will have six months to make their decision, and I hope they will approve it.
A couple of interesting things about the most recent study of Probuphine relative to the earlier studies. This was a study that the FDA asked us to do in their Complete Response Letter after we initially submitted our NDA in late 2012. In March 2013, we had an FDA advisory committee meeting, where they had a 10-4 vote in favor of approving Probuphine based on the data we submitted.
We were surprised in April when we got the CRL. And in that they asked us to do one more clinical study to demonstrate the efficacy of our implant in a different patient population—the original population was chronically ill, heavy heroin users. And the FDA basically asked, what if you give these implants to people who are already somewhat clinically stable? They also wanted a more rigorous control protocol.
BD: And what does the procedure look like?
BEEBE: The implant procedure is a 10 or 15 minute procedure. There's a special tool we have in order to put the product underneath the skin in the arm. We train clinicians how to do the procedure and they can do it in their office. It can be the prescriber or someone other than the prescriber—for example, a psychiatrist can have the procedure done by a physician via referral.
Potential beyond opioid addiction
BD: WHat are some of the other products in the pipeline?
BEEBE: We're working on a Parkinson's product next using the ProNeura technology. That's really the platform for Titan. We're doing non-clinical studies right now with a drug called ropinirole, which is a dopamine agnoist. It's a GlaxoSmithKline drug for the treatment of Parkinson's and restless leg syndrome.
And the reason we chose Parkinson's is because this is a disease that is sort of ideal for an implant tech nology like this. Especially because recent studies have shown that if you continuously stimulate a dopamine receptor system, you achieve a more physiologic dopamine release versus what you get with the oral form. AbbVie, for instance, has developed a levodopa pump that goes in the abdomen.
Right now, we're doing non-clinical animal studies for that treatment. We plan to file the IND in the first half of next year, and then have a proof of concept study started in the second half of next year. We also have some other drug candidates and targets that we haven't spoken about publicly yet.
BHONSLE: It's very versatile. The key is the dosing for the product. That's really the major restriction, otherwise it's very versatile. You just need products that require a stable dose. In our case, we have to find compounds that are already off-patent, otherwise you have to go to somebody else. And we may look at that down the road.
Overcoming the market hurdle for new tech
BD: It takes a lot of time to get the market to really go along with new types of technologies and delivery systems like this. What are some of the challenges of convining the market to use this?
BHONSLE: In some ways, when you think of it, implants are not new. The first implants that were commercialized were really for birth control, which came out way back in the 80s. That had a rough start—some of the training that was required for physicians to do all of this work wasn't quite there at that stage. So that sort of gave a bad rep to implants. Instead, most pharma companies went to things like injectables, time-release drugs, because those were a bit easier. The problem with those is that they're time-limited—you can maybe formulate a biweekly or monthly injectable. But you can't stop therapy, either.
Today, when you see an implant, and you say, oh wow, that's a neat idea! They no longer react like that, because we've done a lot of clinical work that shows as long as your provide the right training, they're willing to use it. In the medical community, there is acceptance, and we've done market research that shows that.
The key in commercializing this becomes one of training. It's very important, and it has to be very systematically rolled out so you're not trying to rush people. I see implants really coming back into vogue these days as a new technology that can provide long-term therapy in chronic settings. It is no longer thought of as an unsafe approach—especially the non-biodegradable ones, where you can stop treatment at any time.
BEEBE: And you know, for doctors, it's another procedure, so they get to charge for that. So they like that!
BHONSLE: Payers like Medicaid, private insurance, see some value in something like this for addiction in the market research we've done. I think the time is right for implants.
BEEBE: Patients like it, too, because they don't have to think about taking it. Compliance is a problem in all chronic conditions, especially in addiction. In the addiction world, the huge benefit is you really reduce diversion and misuse, because buprenorphine is an opioid, an abused opioid. And these things are not as abuse-deterrent as people like to think. And that's one of the reasons the FDA gave us a priority review, because it's a lot easier to go online and score than it is for a patient to dig out our implant.