Saturday, January 7, 2012

Guest: Persevering On NP001

A few days ago my friend, who goes by the handle Persevering on the TDI Forum, posted an evaluation of the PALS who have been self-reporting their experience with the Neuraltus Phase 2 trial of NP001 (which I have discussed here in the past). While the data looks exciting, I must caution that this isn't official data and makes some assumptions which, if wrong, could totally invalidate the evaluation. However, I have enough faith in Persevering to bring this to your attention. For those who don't have Patients Like Me accounts, I reproduce the graphs here.

##########
I have analyzed the NP001 phase 2 data from PLM to date.

I am aware of 37 PLM members who have participated in the trial and 34 who have entered sufficient data to track progress. This is roughly 1/3 of the listed full trial enrollment, and offers a great sample to predict actual trial results. The trial consists of 6 infusion cycles over 21 weeks (147 days), followed by 4 follow-up visits adding 16 more weeks. 13 have completed dosing. 11 will complete within 4 weeks, and all within 8 weeks.

In my thinking, since each infusion cycle is 4 weeks total, the first non-dosing follow up at week 25 (175 days) ends the dosing phase, and I have chosen to review data to day 175 in terms of FRS change. The variable of interest is FRS slope, and is very commonly used to evalauate efficacy for ALS clinical trials. For example, it was used in the recent report of Dexpramipexole phase 2 data, and was used for the official Lithium clinical trials in the US.

FRS for all 37 reporting

In my opinion it is possible to review reports of side effects for commonality to approximate those getting drug (either dose) versus placebo. I do not believe it is 100% accurate, and I also expect those getting a higher dose to have more or greater side effects, but it is not entirely possible to segregate the drug groups (high vs. low). Some may not be prone to side effects on drug and others could experience "nocebo" effects, so again this is not a true substitute for unblinding, which should occur later and allow a timely re-analysis of PLM data.

With that assumption/disclaimer, the summary statistics are:
(Green is improved FRS score, yellow is stable FRS down to -0.49/mo, and red is loss of FRS)

With side effects:

  • n = 20
  • Mean ALSFRS-r slope: 0.00
  • Standard Deviation ALSFRS-r slope: 1.24

FRS for those reporting side effects

Without side effects:

  • n = 14
  • Mean ALSFRS-r slope: -1.01
  • Standard Deviation ALSFRS-r slope: 0.68

FRS with no side effects

Comparison: 100.4% mean improvement

2-tailed t-test p-value for difference = 0.0093

The most exciting outcome to me is that the difference in progression rate is very statistically significant (p<0.05), even with only 34 data points! This would be unprecedented for a phase 2 ALS clinical trial. For example, the recent exciting report regarding Dexpramipexole, with a 31% mean improvement versus placebo in the first 12 weeks had a p-value ~ 0.20, a value 4 times higher than acceptable to conclude drug is better than placebo, by convention (based on a sample size of 53).

There is rumor of an official NP001 trial efficacy review soon, based on all data available on January 24, 2012. Let's hope for statistical significance there as well, and potentially FDA accelerated approval, as occurs for cancer and HIV drugs.
##########

Thanks to Persevering for the work and for the guest-blog!

3 comments:

  1. Eric,
    Really did not look over your site so may already be aware of what I am to write. Vitamin D3 in adequate doses, goverment will argue toxic doses but then again they have approved Vitamin D2 which is for plants and mushrooms is ok. That despite research that shows it is not as good as D3. At any rate I have treated several thousand patients with it at 30,000 IU's per day with excellent results. it restore appropriate sleep cycle which in my opinion is key to restoring health. Lack of restorative sleep is killing our country. Since the only way to receive adequate Vitasmin D3 is through ultraviolet light exsposure(summer in northern latitutes) or supplimental capsules! Also Omega 3 at least 4000 mgs perday. It takes time but over the following months weight is returned to normal, sleep quality is restored and in multiple other ways health is improved!
    Judson Jeffrey Somerville MD, FABA, SPM, DAAPM, FIPP

    ReplyDelete
  2. ENV - do you have any thoughts on when NP-001 trial data will come out? Hardly any chatter about this anymore .....

    Thanks!



    ReplyDelete
    Replies
    1. The Phase 2 officially ends in October, when the database will be "locked and scrubbed". This means no more data entered and any erroneous data from typos up to people who dropped out will be fixed or removed. Then analysis starts followed by preparation of the report. I think the earliest we could hear/see something would be in December (but I have nothing to do with that process so don't hold me to it).

      Delete