About three years after Eli Lilly ($LLY) threw in the towel on the late-stage Type 1 diabetes drug teplizumab, a pair of high-profile academic investigators says they have landed clear efficacy data demonstrating that the drug was "strikingly effective" in preserving insulin-producing beta cells in a large segment of early-stage patients.
The researchers, including UCSF vice chancellor Jeffrey Bluestone, recruited 52 newly-diagnosed patients--most under the age of 14--and treated them with teplizumab for two weeks and then again a year later. The drug is an anti-CD3 monoclonal antibody. The trial participants were compared with a group of patients who were not treated with the drug, with the investigators tracking a read-out on C peptide, produced in the pancreas, as all patients were provided daily injections of insulin.
The treatments helped slightly fewer than half of the patients, the investigators say, adding that it appears that patients who retained relatively good control of their blood sugar were helped the most. Type 1 diabetes is driven by an errant immune system attack on beta cells, destroying patients' ability to produce needed insulin. And the investigators say they are now targeting a Phase III study.
"The benefits of treatment among the patients who still had moderately healthy insulin production suggests that the sooner we can detect the pre-diabetes condition and get this kind of drug onboard, the more people we can protect from the progressive damage caused by an autoimmune attack," said Bluestone, who was joined by Yale professor Dr. Kevan Herold as a collaborator.
Remarkably, this is the same treatment that Eli Lilly dumped back in the fall of 2010 after reporting a big failure in Phase III. Lilly in-licensed the drug from MacroGenics for $41 million upfront and a cool billion dollars in milestones, marking it as one of its top diabetes prospects.
But Lilly scrubbed the program after the independent monitoring committee concluded that the drug failed to hit the efficacy goal, a composite of a patient's total daily insulin usage and HbA1c level at 12 months. That triggered the decision to suspend dosing in another Phase III as well as an early-stage study that was under way.
"Many things were different" this time around, Bluestone tells FierceBiotech in an email. Changes include the patient population, endpoints and dosing.
Type 1 diabetes isn't as prevalent as Type 2, but 30,000 new patients are diagnosed every year, adding to a population of about 3 million.
There's no mention of Lilly in Rockville, MD-based MacroGenics' web page for teplizumab, but the company notes that in June, 2011, The Lancet published the results from Protégé, a Phase III clinical study of teplizumab in T1D. "The primary clinical endpoint was not met. However, exploratory, post-hoc analyses suggest that teplizumab, an anti-CD3 monoclonal antibody, when used in a full dose regimen, may preserve C-peptide and increase the percentage of patients requiring very low doses of insulin compared to those on placebo. In addition, these analyses identified certain subpopulations to be studied in future clinical trials."
MacroGenics says it controls the worldwide rights to the drug.
- here's the press release
Special Report: Top diabetes drug pipelines of 2012