Posts Tagged ‘ALKS 5461’


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Prisoner death from drug withdrawal:

In my blog entry on October 20, 2015, I discussed the horrible death from drug withdrawal suffered by David Stojcevski in the Macomb County, Michigan, jail. I’ve been scouring the internet looking for updates on the lawsuit the family has filed against the county, but haven’t found anything. However, I’m pleased to find many news stories about this awful incident, which helps to keep the issue of medical treatment of prisoners in the news. This is something we must change. Incarcerated people should not be allowed to die from drug withdrawal!

Bad legislation:

On April 12, 2015, I blogged about NC bill S297, which is legislature intended to make drug use by a pregnant woman a criminal act. Regrettably, this sorry and misguided piece of legislation was passed on its first reading in the NC senate. It’s now been referred to the Committee on Rules and Operations of the Senate. If you live in NC, when you vote, remember that Republican Brent Jackson presented this bill, which I believe will keep pregnant women from seeking medical care during pregnancy if they have the disease of addiction. This bill is not good for society, pregnant women, and especially not good for fetuses.


I’ve written a few blog entries (September 2, 2011; March 30, 2013; May 21, 2013; and November 7, 2015), about Probuphine, implantable small rods that deliver buprenorphine into a patient’s bloodstream over six months.

In January of 2016, an advisory committee to the FDA voted to recommend Probuphine for approval by the FDA for the treatment of opioid addiction. The FDA is expected to hold its vote at the end of this month. You will recall that despite a similar recommendation last year, the FDA did not approve this implant, stating more study was needed, especially on patients who were stable at lower dose of buprenorphine.

This time, Titan Pharmaceuticals is seeking approval in patients who are stable on 8mg of the sublingual buprenorphine or less per day.

Of the minority of people on the advisory panel who voted no to the recommendation, concerns were expressed about identifying appropriate patients for this medication, and risks of both implantation and removal of the rods.

I’m still not clear if there will be changes to the rules for implantation and removal of the Probuphine rods. For a buprenorphine prescriber to be able to offer Probuphine, she would have to take a training class for the procedures for implantation and removal. This requires time away from work, to meet an uncertain demand for this product. Not all doctors who prescribe buprenorphine will want do this procedure anyway.

If I want to do this procedure in my office, how to I get the implants? Do I have to buy them, and wait for the patient to pay me back? Do I write a prescription and have the patient pick them up at the pharmacy? Will insurance cover the medication and the procedure? If yes, how long would I have to wait for payment from these companies? I’ve been able to stay in business at my private office by keeping overhead pared to a minimum, so if Probuphine requires an investment by me, I may decide it’s not worth my time and effort.

Hepatitis C treatment

As described in my July 3, 2015 blog entry, the CDC recently reported a surge in the numbers of U.S. citizens who have contracted Hepatitis C. Now another drug has entered the market to treat Hep C, but remains extremely expensive. Earlier this year, Merck pharmaceutical company launched a new Hep C drug called Zepatier. It’s an oral drug that costs an estimated $54,000 for a twelve week course, compared to $80,000 for a similar course of Harvoni. However, early reports say Zepatier cure rates may not be as high as Harvoni’s, so we await more information.

Many health insurance systems can’t afford to pay this much money for treatment of their insured, and so many people infected with Hep C have found their insurer refuses to pay for this new treatment that cures Hep C in most patients. Without insurance, few people could shoulder that expense themselves.

So we have another treatment option, and a little bit less expensive. Let’s hope this trend continues.

ALKS 5461

In my blog post from January 17.2015, I reported a new drug on the horizon that was hoped to be a novel treatment for resistant depression. This medication, known as ALKS 5461, contains buprenorphine (just like Suboxone, Subutex) and samidorphan, a new opioid receptor blocker. The medication was theorized to treat depression by the buprenorphine’s antagonistic action on the kappa receptors, and the samidorphan would serve to block the effect of buprenorphine on opioid receptors, so that the patient would not develop an opioid dependency.

Unfortunately, ALKS 5461 failed to show benefit in two phase III clinical trials, leading Alkermes stock to fall when this data was announced in January of 2016. Despite these results, Alkermes is reported to be continuing research into this potential new medication for depression.

Buprenorphine for Depression: ALKS 5461


Many of my patients have asked me if their medication also treats depression, since they noticed a lifting of their mood after starting buprenorphine (Suboxone, Zubsolv) for the treatment of their opioid addiction. I told them I thought they felt less depression because their brains no longer are in the cycle of intoxication and withdrawal, and also because their life circumstances improved.

Maybe I’m wrong about this.

A new product containing buprenorphine may soon be marketed for depression, and by that I mean just depression, not addiction and depression. Alkermes, the same company that had a disappointment with their depot buprenorphine product last year, started Phase 3 studies last summer on their new product, ALKS5461, after their Phase 1 and 2 studies had positive results.

This product under study contains buprenorphine and a new opioid blocker owned by Alkermes, called samidorphan. In theory, the samidorphan blocks the opioid receptors, leaving only kappa receptors open to buprenorphine. Buprenorphine then attaches to kappa receptors, where it acts as an antagonist. Kappa receptors are usually acted on by dynorphins, opioid peptides that stimulate kappa receptors and cause depression. Dynorphins may also be involved in the stress response, so if buprenorphine can block these kappa receptors, theoretically mood would improve.

The phase 1 and Phase 2 trials of ALKS 5461 showed rapid improvement in the mood of patients already taking antidepressants. These were small studies but of relatively high quality, with double-blinding and placebo control, so Phase 3 studies were started quickly. We won’t know results of the phase 3 study for some time, since the study won’t be over until summer of 2016, so I wouldn’t expect data until 2017.

This new medication is being studied as an adjuvant to the treatment of depression, which means it’s not meant to be used alone, but with established medications in the SSRI (selective serotonin reuptake inhibitors like paroxetine, sertraline, etc.) and SNRI (selective norepinephrine-serotonin reuptake inhibitors like venlafaxine, etc.) groups. Alkermes hopes to get it approved for treatment-resistant depression.

Alkermes is also studying ALKS 5461 as a possible treatment for cocaine addiction, though no data are available on that yet.

Theoretically, this preparation wouldn’t cause opioid addiction because the buprenorphine will be blocked from attaching to the opioid receptor. That makes sense to me, but I also know people are very different. My biggest concern when reading about this new preparation is that real life isn’t as precise as we would like for it to be.

My big questions are: What if some of the patients get an opioid effect from the buprenorphine in the ALKES 5461 product? Do we know for sure that the blocker, samidorphan, will bind to every human mu opioid receptor? Are there genetic differences that will influence response and addiction potential? We already know that people who have major depressive disorder are at increased risk for addiction, and it would be bad if these people developed an opioid addiction while being treated for depression.

On the other hand, depression can be a devastating illness. This new medication will be intended for people who don’t get responses to currently available antidepressants. These patients probably feel desperate for any improvement in their mood, and are willing to accept the risk of unintended complications.

If the Phase 3 studies show good results and this medication gets approved to manufacture and market, it would be a novel way to treat depression. I’m fascinated to see what will happen.