PRODUCT X (DO)
Mechanism

of Action

 PRODUCT X binds to CD3 (a cell surface antigen present on T lymphocytes) and may involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes. PRODUCT X leads to an increase in the proportion of CD8+ regulatory and  exhausted T cells in peripheral blood.
Indications Delay the onset of clinical type 1 diabetes (Stage 3 T1D, insulin-dependent) in adults & pediatric patients 8 years of age & older with preclinical disease (Stage 2) which is defined by the presence of at least 2 T1D-related auto-antibodies & dysglycemia not yet requiring insulin replacement.
Dosage & Administration
  • IV infusion over a minimum of 30 minutes, once-daily for 14 consecutive days.
  • Dosage is based on the body surface area of the patient and titrates up over the first 4 days, with maintenance dosing from days 5-14.
  • Treatment can take place at an infusion center, at home, or in a hybrid manner (starting treatment at infusion center / completing treatment at home) based on HCP and patient preference
Efficacy Significantly delayed the median time to the development of Stage 3 T1D from 25 months with placebo to 50 months with Product X

Clinical trial data Placebo Product X Product X effect
Primary endpoint : Median time from randomization to stage 3 T1D diagnosis, among those who advance to stage 3 25 months 50 months 25 months delay of onset
% of patients free of clinical / stage 3 T1D after 50 months 28% 55% 27pp lower clinical disease rate
Extended data shows ~50% of patients free of clinical / Stage 3 T1D at 5 years (vs.20% for placebo)

Extended follow-up study data Placebo Product X Product X effect
Primary endpoint : Median time from randomization to stage 3 T1D diagnosis, among those who advance to stage 3 27.1 months 59.6 months 32.5 months delay of onset
% of patients free of clinical / stage 3 T1D at 5 years 20% ~ 50% 30pp lower clinical disease rate
Safety & tolerability
  • Safety has been tested in over 1,000 patients.
  • Most side effects were Grade 1 or 2; all resolved without sequelae.
  • In addition to the most common adverse reactions (right), other main side effects seen in previous trials for PRODUCT X vs placebo are:
    •   Cytokine release syndrome (2% vs 0%, respectively)
    •   Serious infections** (9% vs 0%, respectively)
    •   Hypersensitivity reactions; serum sickness (2% vs 0%, respectively)

Notes: *Lymphopenia began resolving after 5th day of dosing and returned to baseline by Week 6; **Serious infections included cellulitis, gastroenteritis, pneumonia, and wound infection.

 Common adverse reactions

Adverse reaction Placebo PRODUCT X
Lymphopenia* 6% 73%
Rash 0% 36%
Leukopenia 0% 21%
Headache 6% 11%
Neutropenia 3% 7%
Increased alanine aminotransferase 3% 5%
Nausea 3% 5%
Diarrhea 0% 5%
Nasopharyngitis 0% 5%