Nemifitide
Nemifitide (INN 00835), subcutaneous pentapeptide antidepressant, development ceased
Written by Aaron CuhaReviewed Sep 2026
Also known as: INN 00835, INN-00835, Netamiftide
A pentapeptide antidepressant injected daily for 5 to 10 days, tested in three small placebo controlled trials (52, 55 and 81 people) between 2000 and 2006 whose positive findings rest on post hoc plasma level groupings, a single post-treatment timepoint and a severity subgroup. No confirmatory trial was published and development stopped.
Overview
Nemifitide is a synthetic five amino acid peptide, a modified analogue of melanocyte inhibiting factor (MIF-1), developed by Innapharma as a rapid acting antidepressant given by subcutaneous injection in short courses. It was called INN 00835 in early papers and briefly netamiftide. Five phase 1 studies gave single and multiple doses of 18 to 320 mg to more than 100 healthy volunteers; the peptide was absorbed within 10 minutes and eliminated with a half-life of 15 to 30 minutes, and the only drug related adverse events were transient pain and redness at the injection site at the highest doses.
Three randomised placebo controlled trials in major depression were published. A 52 person pilot (2000) gave 0.2 mg/kg daily for 5 days and reported that patients whose plasma level exceeded 5 ng/mL improved more than placebo, a comparison defined after the fact by drug level rather than by randomised group; the authors note a large placebo response. A 55 person trial (2001) gave 18 mg daily for 5 or 10 days and reported 89 percent responders among patients with peak plasma levels at or above the mean versus 40 percent below it, again a post hoc split. The largest, an 81 person multicentre trial (2006), compared 30 and 45 mg daily for two weeks with placebo and reported superiority of the 45 mg dose at a single timepoint one week after treatment ended, with statistical separation only in the exploratory subgroup with baseline HAM-D above 22. In all three, tolerability was good, with no dropouts for adverse events. An open label study in 25 people with chronic refractory depression reported 11 responders, and a 27 person open label re-treatment extension reported 18 responders. The peptide's own authors called the 2006 trial a proof of principle study.
No confirmatory trial was published, no trial of nemifitide has ever been registered on ClinicalTrials.gov, and Innapharma's programme ended. In rats bred for depression-like behaviour, nemifitide increased swimming in the forced swim test at low and high but not intermediate doses. Nemifitide has no regulatory status anywhere and is a historical entry.
Mechanism of action
In people, the only mechanistic measurement is a 1999 study reporting a change in platelet serotonin uptake in treated patients, and the pharmacokinetics: rapid absorption, a half-life of 15 to 30 minutes, dose proportional exposure and no accumulation over five daily doses. How a peptide that is gone from the blood within an hour would produce a mood effect lasting weeks was never established. In animals, nemifitide is described as an analogue of MIF-1 (Pro-Leu-Gly-NH2), a hypothalamic tripeptide with antidepressant-like effects in rodent screens, but its receptor is not identified. In Flinders Sensitive Line rats it increased forced swim test activity at 0.025 to 0.3 mg/kg and at 3 to 15 mg/kg but not in between, an inverted U dose response the authors report without explanation.
Human evidence
188 patients in three small randomised placebo controlled trials, about 50 more in two open label studies, and more than 100 healthy volunteers in phase 1. The positive findings in the controlled trials come from post hoc plasma level groupings, a single post-treatment timepoint and an exploratory severity subgroup. No confirmatory trial was published.
- Phase 1 (2002): more than 100 healthy volunteers, 18 to 320 mg subcutaneously, half-life 15 to 30 minutes, injection site reactions at the top doses only.
- Pilot RCT (2000): 52 patients, 0.2 mg/kg for 5 days. Separation from placebo reported only for patients whose plasma level exceeded 5 ng/mL, a post hoc grouping. Large placebo response noted by the authors.
- RCT (2001): 55 outpatients, 18 mg for 5 or 10 days. 89 versus 40 percent responders split by peak plasma level, again post hoc.
- Multicentre RCT (2006): 81 patients, 30 or 45 mg on weekdays for 2 weeks. 45 mg superior to placebo at one timepoint, a week after treatment ended; separation only in the subgroup with baseline HAM-D above 22. No dropouts for adverse events.
- Open label (2008): 25 refractory patients, 11 MADRS responders, re-treatment over up to 660 days in 9 sustained responders.
- Open label re-treatment extension (2003): 27 patients from the phase 2 programme, 18 responded to re-treatment, mean interval between courses 3.3 months.
- ClinicalTrials.gov, September 2026: no trial of nemifitide has ever been registered.
What this does not tell you: None of the three controlled trials demonstrates efficacy on a prespecified primary comparison of randomised groups. Splitting treated patients by plasma level after the fact, or by baseline severity, or picking the timepoint of peak effect, are all analyses that can manufacture a difference from noise, and the authors of the largest trial said as much by calling it a proof of principle. The trials were 2 weeks of dosing with 4 to 6 weeks of follow up in outpatients; nothing is known about longer use. Good tolerability in roughly 300 people is real but small. The compound was never tested by any route other than subcutaneous injection.
Reading the research record
Nemifitide's record is the record of a small company that ran the early trials it could afford and did not find, or could not fund, the large one that would have settled the question. Innapharma sponsored every study. The 2002 pharmacokinetics paper describes the compound as in phase 2/3 trials; no phase 3 result was ever published, and ClinicalTrials.gov, which became mandatory for most trials in 2007, holds no record under this name, so whatever happened next happened before registration was required or did not happen at all. The Curr Opin Investig Drugs profile of 2003 and the antidepressant pipeline reviews of 2008 and 2009 discuss it as a candidate; after that it disappears from the literature.
The honest reading is that a peptide with a plausible mechanism and a clean safety record produced encouraging but analytically fragile results in about 190 patients and was never tested properly. That is not evidence it does not work, and it is not evidence it does. It is a stopped programme. Vials sold as nemifitide today are of a compound that has not been in a human trial in roughly two decades and whose dose, schedule and duration of effect were never settled.
The evidence, charted
Fig. 1 · evidence composition
5of 6 citations (83%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 6 distinct years, 2000 to 2008, counted from the citation list on this page. The newest citation on file is from 2008, more than five years ago; the published record may have gone quiet.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2006
Efficacy and safety of 30 mg/d and 45 mg/d nemifitide compared to placebo in major depressive disorder
81 outpatients with major depression randomised to 30 mg/day, 45 mg/day or placebo by subcutaneous injection on weekdays for 2 weeks, followed for 4 more. Primary measure MADRS change. The authors report superiority of 45 mg over placebo at the timepoint of peak effect, one week after treatment ended, and separation from placebo only in the exploratory subgroup with baseline HAM-D above 22. No dropouts for adverse events. Described by its authors as a proof of principle study. Developer funded (Innapharma).
International Journal of Neuropsychopharmacology - Human2000
A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression
52 patients (26 drug, 26 placebo), 0.2 mg/kg subcutaneously for 5 days, followed 4 weeks. Response correlated with plasma concentration 1 hour after dosing; patients above a 5 ng/mL threshold differed from placebo, a grouping defined after randomisation. The authors note a relatively large placebo response and call for confirmation in larger trials. Developer funded.
Journal of Affective Disorders - Human2001
Double-blind, placebo-controlled study of INN 00835 (netamiftide) in the treatment of outpatients with major depression
55 outpatients: 22 given 18 mg daily for 10 days, 11 for 5 days then placebo, 22 placebo. 89 percent responders among patients with peak plasma level at or above 45.7 ng/mL versus 40 percent below it, a post hoc pharmacokinetic split rather than a randomised comparison. No significant adverse effects. Developer funded.
International Clinical Psychopharmacology - Human2008
Clinical effect of nemifitide, a novel pentapeptide antidepressant, in the treatment of severely depressed refractory patients
Open label, single centre, 25 patients with chronic refractory depression given 40 to 240 mg daily for 10 to 20 doses. 11 responded on the MADRS, 7 of them sustained through the acute phase; 9 sustained responders were re-treated as needed over up to 660 days with a mean response duration of about 2 months. Uncontrolled. Developer funded.
International Clinical Psychopharmacology - Human2002
Clinical pharmacokinetic studies with INN 00835 (nemifitide), a novel pentapeptide antidepressant
Five phase 1 studies, more than 100 healthy volunteers, single and multiple subcutaneous doses of 18 to 320 mg. Peak plasma level at 10 minutes, half-life 15 to 30 minutes, dose proportional exposure, no accumulation over 5 daily doses. Drug related adverse events limited to transient injection site pain and redness at 240 and 320 mg. Developer funded.
Biopharmaceutics and Drug Disposition - Animal2004
Antidepressant-like effects of a novel pentapeptide, nemifitide, in an animal model of depression
Flinders Sensitive Line rats treated for 5 or 14 days. Nemifitide increased forced swim test swimming at 0.025 to 0.3 mg/kg and 3 to 15 mg/kg but not at 0.4 to 2.4 mg/kg; 0.3 mg/kg matched desipramine at 5 days. Rat data only.
Psychopharmacology
Frequently asked questions
Did nemifitide work as an antidepressant?
Three small placebo controlled trials in 52, 55 and 81 people reported positive findings, but each rests on an analysis defined after the fact: grouping by plasma drug level, a single timepoint a week after treatment ended, or a subgroup with more severe depression. The authors of the largest trial called it a proof of principle. No confirmatory trial was published.
Why did development stop?
No published source gives a reason. Innapharma described the compound as in phase 2/3 trials in 2002, published the 81 person trial in 2006 and an open label study in 2008, and then nothing. No trial was ever registered on ClinicalTrials.gov and no regulatory submission has been located.
Was it safe?
In roughly 300 people across phase 1 and phase 2, the only drug related adverse events were transient pain and redness at the injection site at high doses, and no patient left a trial because of side effects. That is a good short term record in a small number of people, not a safety profile.
How is it related to Semax or Selank?
Only loosely. All three are short synthetic peptides derived from natural neuropeptides and studied for mood and cognition. Nemifitide is a MIF-1 analogue tested in Western placebo controlled depression trials; Semax and Selank are ACTH and tuftsin analogues from the Russian pharmacopoeia with a different evidence base.