FDA Approves New Drug Implant

By Pat Anson, Editor

The U.S. Food and Drug Administration has approved the use of a new drug implant for the treatment of opioid addiction.  Probuphine is the first implant of its kind approved by the agency and could potentially be a game changer for other medical conditions such as chronic pain that require steady doses of medication around-the-clock.

Probuphine is designed to be inserted into the arm beneath the skin, where it delivers a low dose of burprenorphine directly into the bloodstream for up to six months.  

Buprenorphine is an opioid itself, but when combined with naloxone, the medication reduces cravings for opioids. Until now the drug has only been available as a pill or film strips placed under the tongue.

For many years buprenorphine was sold exclusively under the brand name Suboxone, but several pharmaceutical companies have entered the lucrative addiction treatment market and now make versions of their own. As many as 2.3 million people who are dependent on opioid pain medication or heroin could benefit from buprenorphine treatment,

FDA approval was a major win Braeburn Pharmaceuticals and its partner, Titan Pharmaceuticals (OTC: TTNP), which holds the rights to the implant technology. Titan and Braeburn were stunned in 2013 when the FDA denied approval of the implant and asked for new clinical studies proving Probuphine’s effectiveness.  

Results from a recent Phase III study showed that over 85% of the patients who had the implant abstained from using illicit opioids for six months, compared to about 72% of patients who used buprenorphine film strips that were taken daily.

"Opioid abuse and addiction have taken a devastating toll on American families. We must do everything we can to make new, innovative treatment options available that can help patients regain control over their lives,” said FDA Commissioner Robert Califf, MD. “Today’s approval provides the first-ever implantable option to support patients’ efforts to maintain treatment as part of their overall recovery program.”

Expanding the availability of addiction treatment is a major goal of the Obama administration. The White House has asked Congress for an additional $1.1 billion to fight opioid abuse, with much of the money earmarked for addiction treatment. The administration has also proposed doubling the number of patients that doctors can treat with buprenorphine from 100 to 200.

Buprenorphine can be abused and is a popular street drug that is used to get high or to ease withdrawal pains from illegal opioids such as heroin. An implant will be much more difficult to abuse, since it can’t be crushed or liquefied for snorting or injecting. It’s also less likely to be diverted.

Probuphine is expected to cost about $1,000 a month. It consists of four, one-inch-long rods that are implanted under the skin on the inside of the upper arm. Administering Probuphine will require special training because it must be surgically inserted and removed.

The most common side effects are pain at the implant site, as well as itching, redness, headache, depression, constipation, nausea, vomiting, back pain, toothache and oral pain. The FDA is requiring post-marketing studies to establish the safety and effectiveness of the implants.

Probuphine was developed using a patented implant technology called ProNeura, which is designed to provide continuous levels of medication in the blood. Titan is also developing implants to treat Parkinson’s disease and hypothyroidism, and its CEO told Pain News Network that ProNeura could also potentially be used to deliver pain medication.

“Clinical studies will need to be done to establish the ability, but the drug levels can certainly be delivered that are going to be beneficial for treating chronic pain,” said Titan CEO and President Sunil Bhonsle. “There are many applications for this technology and I think the medical community is now more in tune with looking at long-term delivery technology in the chronic disease setting.”

“It is part of our plan to move into pain because pain and opioid addiction are so interconnected and we think there are ways, by treating patients with a less abuse-able formulation, you could actually help alleviate the addiction problem,” Behshad Sheldon, President and CEO of Braeburn, told PNN in an earlier interview.

FDA Nearing Decision on Drug Implant

By Pat Anson, Editor 

The U.S. Food and Drug Administration is expected to finally make a decision next month on a new drug delivery system to treat opioid addiction – an implant that could also be used someday to treat pain and other chronic illnesses that require steady doses of medication.

The latest results from a Phase 3 double blind study of a buprenorphine implant called Probuphine would appear to boost its chances of winning FDA approval. Titan Pharmaceuticals (NASDAQ: TTNP) said over 85% of the patients who had the implant for six months abstained from using illicit opioids, compared to about 72% of patients who used oral buprenorphine film strips that were taken daily.

The study findings were recently presented at the annual meeting of the American Society of Addiction Medicine in San Francisco.

"This was the first head-to-head comparison study of Probuphine and sublingual buprenorphine, demonstrating the efficacy of a long-acting six month buprenorphine implant," said lead investigator Richard Rosenthal, MD, Professor of Psychiatry and Medical Director of Addiction Psychiatry at the Icahn School of Medicine at Mount Sinai. “If approved, Probuphine could help expand access to medication to treat opioid use disorders, providing people with a new option."

titan pharmaceuticals image

Probuphine is about the size of a matchstick and is implanted under the skin. For six months it delivers a steady dose of buprenorphine, a weaker acting opioid that’s long been used as an addiction treatment drug sold under the brand name Suboxone.

There are many advantages to an implant. The dosage is controlled and there’s little risk of abuse, diversion or overdose. Users also never have to remember to take a pill.

Probuphine’s path to the marketplace has been rocky at times. Titan and its partner, Braeburn Pharmaceuticals, were stunned in 2013 when the FDA denied approval of the implant and asked for a new clinical study proving Probuphine’s effectiveness.  

Positive results from a Phase 3 trial were submitted in 2015 and in January of this year an FDA advisory committee voted 12 to 5 in favor of approving the implant. But then the agency added another delay by extending its decision date to May 27.  

The time may be ripe for approval this time around, as the FDA is under intense political pressure to do more to address the nation's opioid abuse epidemic. The Obama administration has proposed a rule change that would double the number of patients that a doctor can treat with buprenophine from 100 to 200. And Congress is considering funding proposals that would allocate another $1 billion to the war on drugs, with most of the money spent on addiction treatment.

Probuphine was developed using a patented implant technology called ProNeura, which is designed to provide continuous levels of medication in the blood. Titan is also developing implants to treat Parkinson’s disease and hypothyroidism, and its CEO told Pain News Network in a recent interview that ProNeura could also potentially be used to deliver pain medication.

“Clinical studies will need to be done to establish the ability, but the drug levels can certainly be delivered that are going to be beneficial for treating chronic pain,” said Titan CEO and President Sunil Bhonsle. “There are many applications for this technology and I think the medical community is now more in tune with looking at long-term delivery technology in the chronic disease setting.”

FDA Committee Approves New Drug Implant

By Pat Anson, Editor

An advisory committee to the U.S. Food and Drug Administration has approved a new drug delivery system to treat opioid addiction – an implant that could potentially be used to treat chronic pain and other diseases that require steady doses of medication.

The FDA’s Psychopharmacologic Drugs Advisory Committee voted 12 to 5 in favor of the new drug application for Probuphine, a tiny implant about the size of a matchstick that contains buprenorphine, a drug already used to treat addiction that currently only comes in pills and oral film strips. The FDA is expected to make a final decision on Probuphine next month.

“You can never be 100 percent sure of anything,” said Sunil Bhonsle, CEO and president of Titan Pharmaceuticals (NASDAQ: TTNP), which partnered with Braeburn Pharmaceuticals in developing the implant. “The data clearly shows that this product can be of benefit to this patient population. And we hope the FDA will approve it.”

COURTESY BRAEBURN PHARMACEUTICALS

Once implanted under the skin, Probuphine is designed to deliver a steady dose of buprenorphine for six months. Buprenorphine is a weaker opioid that’s long been used as an addiction treatment drug sold under the brand name Suboxone. While it reduces cravings for opioids, buprenorphoine can also be abused and is prized by addicts as a street drug that can ease withdrawals pains from heroin.

The advantages of an implant are many. The dosage is controlled and there’s hardly any risk of abuse, diversion, or accidental overdose. Users also never have to remember to take a pill.

Probuphine’s path to the marketplace hasn’t been a smooth one. Braeburn and Titan were stunned in 2013 when the FDA denied approval of the implant and asked for a new clinical study proving Probuphine’s effectiveness in treating opioid addiction.

The results of a six month, double-blind clinical trial on 177 patients, found that the implant was more effective than buprenorphine film strips in treating addiction. The implant’s insertion and removal were "generally well tolerated," although nearly one in four patients had a "mild" adverse event at the implant site.

Several members of the FDA's advisory committee, including its chairwoman, voted against approval, saying there was not enough evidence of Probuphine’s effectiveness after six months.   

"New treatment options for the millions of patients and their families suffering from opioid addiction are desperately needed, and we appreciate the Committee's comprehensive review of Probuphine," said Bhonsle. “There are many applications for this technology and I think the medical community is now more in tune with looking at long-term delivery technology in the chronic disease setting. So I think it’s probably accurate to say the time is right to expand the use of these technologies to different settings.”

Bhonsle says Titan is already looking at ways the implant can be used to treat Parkinson’s disease and hypothyroidism, adding that chronic pain could also be treated with an implant.

“Clinical studies will need to be done to establish the ability, but the drug levels can certainly be delivered that are going to be beneficial for treating chronic pain,” he told Pain News Network.    

Implant Could Be ‘Game Changer’ in Pain Treatment

By Pat Anson, Editor

Imagine going to your doctor’s office and getting an implant put in your arm that delivers a steady flow of pain medication for six months.

No more pills. No more trips to the pharmacy. No more worries about your pain medication getting lost or stolen.

That’s the scenario a New Jersey drug maker envisions for its Probuphine implant – tiny rods about the size of a matchstick designed to be inserted subcutaneously under the skin of the upper arm.

Probuphine was developed by Braeburn Pharmaceuticals under a license agreement with Titan Pharmaceuticals (OTC: TTNP), which holds the rights to the implant technology. Both companies have applied to the Food and Drug Administration to have Probuphine approved to treat opioid addiction, but Braeburn’s long term goal is to also have the implant approved for chronic pain.

COURTESY TITAN PHARMACEUTICALS

“We are definitely interested in talking to the FDA about the use of Probuphine in pain,” said Behshad Sheldon, President and CEO of Braeburn.

The active ingredient in Probuphine is buprenorphine, a weaker opioid that’s long been used as an addiction treatment drug sold under the brand name Suboxone. Buprenorphine is also used to treat chronic pain and comes in various forms – pills, patches and film strips – but none as long-acting as an implant.

The advantages of an implant are many. The dosage is controlled and there’s hardly any risk of abuse, diversion, or accidental overdose. You also never have to remember to take a pill.

“We believe a buprenorphine implant could be a really great clinical tool to treat pain,” Sheldon told Pain News Network. “There’s just a peace of mind aspect for the patients. The medicine’s on board and they don’t have to worry about it.”

“I personally would want a Lipitor implant, because I can’t manage to take it three days in a row,” she joked.

Probuphine’s path to the marketplace hasn’t been a smooth one. Braeburn and Titan were stunned in 2013 when the FDA denied approval of the implant and asked for a new clinical study of Probuphine’s effectiveness in treating opioid addiction.

Braeburn recently reported the results of a six month, double-blind clinical trial of Probuphine on 177 patients, which found that the implant was more effective than buprenorphine tablets in treating addiction. The company said the implant insertion and removal were "generally well tolerated," although nearly one in four patients had a "mild" adverse event at the implant site.

“The data from this trial are encouraging and underscore the benefit of longer term medical treatments for patients with opioid addiction. I am confident that the implant, if approved by FDA, will be at least as effective as a sublingual formulation and have the added benefits of reducing problems related to compliance, misuse and abuse,"  said Richard Rosenthal, MD, Professor of Psychiatry and Medical Director of Addiction Psychiatry at the Icahn School of Medicine at Mount Sinai.

Braeburn and Titan plan to resubmit a New Drug Application (NDA) for Probuphine to the FDA in the second half of this year.

Long Term Injection for Pain

Braeburn has formed another partnership with Camurus, a Swedish drug company, to develop an injectable buprenorphine drug to treat addiction and chronic pain -- a single injection that lasts as long as a month. Camurus has already completed successful Phase I and II studies on the drug and both companies hope to start a Phase III trial later this year -- with the goal of seeking regulatory approval in 2016.

“There have been many conversations with expert clinicians and they’ve told us that they think buprenorphine in general, in a non or less abuse-able form of buprenorphine, in either an implant or an injection could really be game changing,” said Sheldon. “It is part of our plan to move into pain because pain and opioid addiction are so interconnected and we think there are ways, by treating patients with a less abuse-able formulation, you could actually help alleviate the addiction problem.”

Sheldon admits a lot more work needs to be done before a buprenorphine implant or injection is available to treat chronic pain.

“We haven’t studied it yet in pain and we haven’t had any conversations yet with the FDA. So there’s a lot more to do to get to that point,” she said.

Another formulation of buprenorphine to treat pain may be coming to the market relatively soon. Endo International (NASDAQ: ENDP) and BioDelivery Sciences (NASDAQ: BDSI) have submitted a new drug application for a buprenorphine film patch to the FDA. The companies are hoping for FDA approval by October of this year.

Although the patch contains much smaller doses than buprenorphine tablets or patches already on the market, the companies say the film is very effective in treating pain because the drug is absorbed through the inside lining of the cheek and enters the blood stream faster.