Adamas Provides Data Update On ADS-5102 - Controlled Release Amantadine
 

Adamas Pharmaceuticals, Inc. today presented data on the safety and efficacy of ADS-5102 for the treatment of levodopa-induced dyskinesia (LID), a serious movement disorder associated with Parkinson's disease treatment. The data, from Adamas' Phase 2/3 EASED study, included assessments of patients receiving ADS-5102 using a metric called the Clinician's Global Impression of Change (CGI-C). The clinicians were asked to assess their impression of the change in a subject's clinical status related to overall Parkinson's disease, including LID. CGI-C is a tool to evaluate a patient's response over time and is routinely used for a number of diseases, including Parkinson's disease.

At the 340 mg dose level there was a statistically significant improvement in overall Parkinson's disease clinical status, including LID, versus placebo as measured by physicians using the CGI-C (p=0.0036).

"These clinician-reported data add to the totality of information we have generated on ADS-5102 and reflect the consistent improvements observed using a number of different outcome measures," said Natalie McClure, Ph.D., Adamas' Senior Vice President of Product Development. "The Phase 2/3 EASED study met its primary endpoint, and we have selected the dose for future development. We are now advancing ADS-5102 into a Phase 3 study, which is anticipated to start later this year."

ADS-5102 is a controlled-release version of the approved drug amantadine. Adamas is developing ADS-5102 initially for treatment of LID, a movement disorder that frequently occurs in patients with Parkinson's disease after long-term treatment with levodopa, the most widely-used drug for Parkinson's disease. Many individuals with late-stage Parkinson's disease suffer from LID, and there are no approved treatments for this disorder. Patients with LID suffer from involuntary movements and reduced control over voluntary movements.

Adamas believes that ADS-5102 may address many of the limitations of immediate-release amantadine by allowing higher daily doses of amantadine to be administered once-nightly without a significant increase in side effects.

In the EASED study, in patients taking ADS-5102, the amantadine plasma concentration achieved in the early morning through mid-day was approximately two-times that reached following administration of immediate-release amantadine, providing symptomatic relief to patients as they engaged in their daily activities. Further, the lower concentrations occurred in the evening, reducing the potential negative impact of amantadine's sleep-related side effects.

http://ir.adamaspharma.com/releasede...leaseID=844065

"At the 340 mg dose level there was a statistically significant improvement in overall Parkinson's disease clinical status, including LID, versus placebo as measured by physicians using the CGI-C (p=0.0036)."

At first sight that sounds like good news, but I would like to know:

1. ADS-5102 is measured against the placebo. Would it not make sense to measure it against immediate release amantadine?

2. Success is reported for the 340mg dose. The trial included also 260mg and 420 mg doses. What was the outcome for these?

3. Success was reported for the change in UDysRS. Other measures were used such as diaries and MDS-UPDRS. Do these also show improvements?

4. It seems to me that the obvious measurement that would be understandable to lay people would be before and after values of daily hours with LID together with standard Parkinson's parameters. What are the size of these improvements?

Clearly the results are less exciting if these other measurements do not show similar improvements.

John

All good questions, John. I don't have a link to actual analytical results, but I do have some notes I jotted down from a conference call, so I can't vouch for 100% accuracy. That being said, this is some additional information that I have:

* Yes, it would be interesting to see results against plain old original Amantadine. I don't know if Adamas has that information, but this trial was not designed that way.

* Both the 340mg and 420mg dose levels significantly reduced LID on the primary endpoint. However, there was no significant improvement from 340 to 420, so the Phase III study will focus only on 340mg. The 260mg group did have a 5 point improvement on the UDysRS, but the result wasn't statistically significant (p=.15). This could possibly change with a larger Phase III sample size, but I don't think they intend to test the lower dosage again. By comparison, the 340mg group had a mean improvement compared to placebo of over 11 points.

* There were many secondary outcome measurements. Not all were significant but many were, including:

- All three doses significantly increased On Time with Troublesome Dyskinesia according to the patient diaries (approximately 3 hours for all doses).
- All three doses significantly improved functional impact as measured by the MDS-UPDRS part IV.
- The drug was generally well tolerated, consistent with the known history of Amantadine use with PD.

I'll post more info if I get it.