May 24, 2010

Reflections on Dotty and Dimebon

Let me make this clear. I am not angry. It is not my intention to blame or vilify Medivation (MDVN) or Pfizer (PFE).

By Bob DeMarco
Alzheimer's Reading Room

I am sitting here reviewing my notes on Dimebon. I am looking at the company press releases. I am also reviewing the many articles I wrote about Dimebon, Aricept, and Namenda.

I am reviewing my notes that I started taking on the Dimebon clinical trial that Dotty entered on January 6, 2010.

On January 6, I wrote that I would not write about or reveal our experience with Dimebon until the end of the 26 week clinical trial phase; and until, we entered the open label extension phase of the clinical trial.

Many of you have been here for a while, so when I wrote about some of the remarkable things that were happening with Dotty you were able to connect the dots. You emailed and asked, is it the Dimebon?

It did appear that something amazing started to happen with Dotty about 4 weeks into the clinical trial.

When I wrote -- Dotty Bingo Alzheimer's -- many of you wrote and asked, is it the Dimebon?

When I wrote -- Philly Cheese Steak and Potato Chips -- some of you asked, is it the Dimebon?

When I wrote -- Not a Ghost of A Chance -- An Alzheimer's Out of the Box Moment -- many emailed me and asked, Dimebon?

Some of you noticed that I started the Dotty Says feature on April 20, almost 15 weeks into the Dimebon clinical trial. This occurred because of the remarkable performance that Dotty evidenced on the memory and behavior tests in the Dimebon clinical trial at the 12 week mark.

The twelfth week is a first major milestone in the clinical trial. Dotty's scores were most likely statistically significant -- positive.

It turns out, Dotty was more engaged with me and others then she had been in years.

In fact, if you took memory out of the equation and only focused on behavior and engagement you might have jumped to this conclusion -- that's my Dotty. Not a full fledged version of the Dotty of a decade ago, but a damn good slightly watered down version. Clearly, Dotty had not acted the way she was Now in many many years.

Let's put it this way. My heart was soaring and to be honest, I had a hard time believing what I was seeing and hearing.

After tweleve weeks in the Dimebon clinical trial, I was really looking forward to week 26. This would be the last major round of testing prior to the open label extension phase.

I was already wondering.

How will Dotty do in the next 14 weeks?

Will she hold?

Will she continue to improve (wo nelly)?

Will she crash and burn?

I was anxiously awaiting the end of July for two reason. First, so I could see the results. Second, so I could start writing about our experience. It wasn't easy containing myself and keeping my promise to remain silent during the entire 26 week clinical trial. I guess you could say I bent the "rule" a bit.

On May 10, Medivation (MDVN) and their partner Pfizer (PFE) pulled the plug on the two clinical trials for moderate to severe stage Alzheimer's patients. They pulled the plug on Dotty and many more patients suffering from Alzheimer's disease.

Medivation and Pfizer used the findings from the Dimebon Connection study to pull the plug. Just so we can be clear, the Connection Study was designed for Alzheimer's patients with mild to moderate Alzheimer's disease -- not moderate to severe Alzheimer's disease.

For a reason known only to Medivation and Pfizer, they decided to continue the Dimebon Concert Study.

So lets see.

Concert is for patients with mild to moderate Alzheimer's. Connection was for patients with mild to moderate Alzheimer's. The Concert study was continued. The Companies canceled the clinical trials that were designed for patients with moderate to severe Alzheimer's. See any disconnect here?

The Concert study is already nearing the completion of data collection. The results should be available in 2011. So, a lot of money has already been invested in Concert. It seems like a risk reward proposition. Spend a little more and see if the results warrant additional investment in Dimebon.

And now to four important issues.

Did Dotty receive Dimebon or the placebo during her time in the clinical trial? Impossible to know for sure. Maybe Medivation will un-blind the study and we will find out at some point in the future.

Was Dotty's crash and burn (she is very sick) caused by the elimination of Dimebon from her medication regimen on May, 10? Impossible to know -- right now. We might learn something from others that were yanked off Dimebon in the weeks and months ahead.

Does the combination of Namenda and Dimebon work for Alzheimer's patients with moderate to severe Alzheimer's? It seemed to be working for Dotty if you assume she had Dimebon. Note: Dotty was in the study testing the combination of Dimebon and Namenda -- A Phase 3 Efficacy Study Of Dimebon In Patients With Moderate To Severe Alzheimer's Disease.

If the clinical trial that Dotty was enrolled in was not completed, how can the companies claim the trial was cancelled due to the "efficacy" of Dimebon. As far as I can determine, there is no existing and completed clinical trial with Dimebon, Namenda and for patients suffering from mild to severe Alzheimer's that failed based on "efficacy".

So far this is the only thing that appears on the Medivation website concerning this issue:

"After thorough review of all available dimebon data, including the disappointing CONNECTION results, Medivation remains committed to determining whether dimebon may offer clinical benefit to Alzheimer's and Huntington disease patients," said David Hung, MD, president and chief executive officer of Medivation. "We will continue to enroll patients in the 12-month Phase 3 CONCERT trial in mild-to-moderate Alzheimer's patients and the six-month Phase 3 HORIZON study in Huntington disease, and will stop our two ongoing Phase 3 trials in moderate-to-severe Alzheimer's disease. In reaching this conclusion, we considered all dimebon data generated thus far, including the negative CONNECTION data, the clinical benefit seen in two prior dimebon trials in mild-to-moderate Alzheimer's disease and Huntington disease, the excellent safety and tolerability profile in all dimebon trials to date covering more than 2,000 patients, the preclinical data consistently showing that dimebon is pharmacologically active, and the potential risks and returns of continuing development for Alzheimer's and Huntington diseases. We believe both the CONCERT and HORIZON studies offer independent pathways to registration, and we will be meeting with the Food and Drug Administration this quarter to discuss the CONNECTION data and obtain guidance on our proposed regulatory path forward."

"We also continue to make progress on our MDV3100 program," continued Dr. Hung. "This year we and our partner Astellas expect to complete enrollment in the Phase 3 AFFIRM trial in advanced prostate cancer patients and to initiate three new trials in earlier-stage prostate cancer, including a second Phase 3 trial. Our cash position remains strong and, based on current assumptions, we expect our cash to last beyond 2012, without regard to whether Pfizer elects to remain in our dimebon collaboration. We also expect to have reported top-line data from the CONCERT, HORIZON and AFFIRM trials by the end of 2012."

Let me make this clear. I am not angry. It is not my intention to blame or vilify Medivation (MDVN) or Pfizer (PFE).

More Insight and Advice for Caregivers
Bob DeMarco is the Founder of the Alzheimer's Reading Room and an Alzheimer's caregiver. The blog contains more than 2,910 articles with more than 652,100 links on the Internet. Bob lives in Delray Beach, FL.

Original content Bob DeMarco, the Alzheimer's Reading Room