This excerpt taken from the NVS 6-K filed Feb 14, 2007.
Late last year, Novartis announced a three-month extension of the US regulatory review of Galvus after the company decided to submit additional clinical data to the FDA. The original regulatory submission to the FDA had included data from approximately 2 800 patients, treated for up to 12 months, and the subsequent submission represented data from an additional 1 000 patient years of treatment with Galvus.
The submission of supplemental data came in response to questions from the FDA about lesions seen on the skin of some monkeys treated with Galvus in a study requested by the agency. In that study, however, monkeys received doses several orders of magnitude higher than the proposed therapeutic dose. The side effects hadnt been seen in previous studies by Novartis in monkeys given a therapeutic dose of Galvus. Moreover, there hasnt been a similar finding in any other species or in any human patient treated with Galvus in clinical trials lasting up to 24 months.
FDA has the right to extend the review period if they believe that a company already has in its possession sufficient data to address concerns the agency may have, Dr. Shannon says. We havent seen anything even resembling this in our patient studies thats why we have submitted the additional data.
Underscoring that confidence, Novartis has embarked on a new round of clinical studies aiming to demonstrate the full potential of Galvus. A study known as GALIANT, involving more than 7 500 people in the US, is comparing safety and efficacy of Galvus and the TZD class of insulin sensitizers in a real-world, primary care setting. Importantly, the GALIANT study will assess the impact
of Galvus in many different patient populations, including the elderly, different ethnic groups, and patients with varying degrees of body mass index.
GALIANT is seeking to confirm results of a smaller study where patients receiving Galvus as monotherapy had significant reductions in blood sugar similar to levels seen in patients treated with rosiglitazone, a drug in the TZD class.
The GLORIOUS program comprises five studies designed to demonstrate the disease modification potential of Galvus. The studies will explore the potential of Galvus both to prevent progression to diabetes in groups at high risk of developing the disease as well as to delay disease progression in people who already have developed type 2 diabetes.
Like GALIANT, the GLORIOUS studies will involve diverse patient populations. One will test the ability of Galvus to prevent progression to type 2 diabetes in Asian patients with impaired glucose tolerance, a major risk factor. Asian populations have a different pathophysiology and a very high conversion rate to diabetes, Dr. Nathwani says.
Were also looking to see if we can stabilize patients with type 2 diabetes by adding Galvus to metformin, the current standard of care, he adds. Most doctors are already using metformin and this study will provide cutting-edge information they want. Often, combination studies only appear years after a new medicine comes to market.
The GLORIOUS program will seek to confirm early indications that treatment with Galvus leads to meaningful reductions in blood pressure of patients, parallel with beneficial effects on blood sugar levels. We plan to look at a novel population of high-risk cardiovascular patients treated with Galvus. Endpoints will include both a reduction in cardiovascular events, as well as development of their diabetes, Dr. Nathwani explains.
It is an area of longstanding interest. Novartis believes that preventing diabetes will also lead to a reduction in cardiovascular consequences.
In parallel, groundbreaking data is expected from NAVIGATOR, an ongoing study in the Diovan megatrial program, that is exploring the possibility of preventing progression of type 2 diabetes and cardiovascular events in people with impaired glucose tolerance.
In the VALUE study, treatment with Diovan reduced new-onset diabetes by 23%, Dr. Nathwani says. Were confident that GLORIOUS and NAVIGATOR will provide definitive evidence that reducing new-onset diabetes can prevent heart attacks and stroke.