EASD: Diabetes Group Supports Stricter Drug Approval Standards - MedPage Today

STOCKHOLM -- Tighter safety standards for approval of diabetes drugs are coming to Europe with the cautious support of the European Association for the Study of Diabetes.

The organization offered a general endorsement of the European Medicines Agency's new guidelines -- now in the interim period waiting for final issuance -- at a press conference here at its annual meeting.

The diabetes organization cautioned, though, about the potential for stifling drug development.

"There are real issues about inhibiting research if requirements are so onerous that no new therapies are brought to market," David R. Matthews, MD, of Oxford University in England, told reporters as chair of the EASD panel that issued the statement.

The EMA's draft guidance document indicated that the agency will strengthen requirements for cardiovascular safety assessment and inclusion of more representative patient populations.

But it has taken a softer position than the FDA, not imposing numeric thresholds for approvability.

The FDA's guidance, issued in 2008 in the wake of the rosiglitazone (Avandia) cardiovascular safety firestorm, included a mandate for:

• Approval of diabetes drugs only with exclusion of a 30% relative increase in cardiovascular events compared with placebo or an active comparator, or of an 80% relative excess of events with a post-marketing study to formally evaluate the risk.
• Data on patients with advanced diabetes, elderly patients, and those with some degree of renal impairment included in the regulatory submission -- groups typically excluded from pivotal trials.
• At least two years of cardiovascular safety data, to include major adverse cardiovascular events as an endpoint with independent adjudication of events.

The EMA also added what the EASD called in its press statement "a more in-depth view for superiority or noninferiority trials with clearer criteria for reporting."

These changes would include requirements for companies to show:

• Add-on and combination studies that compare the novel agent against established ones with robust analysis based on therapeutic targets, nonresponders, and hard outcomes including cardiovascular events as well as heart failure
• Long-term safety
• Improvements in glycosylated hemoglobin, not just reduction of insulin dose or high insulin level
• Data on patients diagnosed with diabetes for longer than five years and analysis of outcomes in patients with microvascular or macrovascular complications
• Studies should include a significant proportion of elderly patients

The EASD supported these changes overall, recognizing that "safety is paramount," as Matthews explained, and approved of the "more generic" approach to complications of therapy.

Concentrating on the risk of myocardial infarction, for example, may miss benefits in prevention of blindness, Matthews noted. And results in elderly diabetics may not apply to teens with type 2 diabetes, he added.

"Regulators need to be cautious of mandating trials in those with established heart disease when the majority of patients treated may not be thus categorized," he said at the press conference.

The final guidance from the EMA was expected to have been released already, but concerns about trial conduct raised by FDA investigation into the RECORD trial of rosiglitazone may have caused delay, Matthews speculated.

The European agency could still spring surprise changes in the final version, but whatever happens, the balance isn't likely to shift to a more laissez-faire approach to approval, according to Matthews.

"After Avandia, [the EMA] is very unlikely to take a lenient view on cardiovascular safety," he told reporters.

The EMA is also expected to issue a verdict Thursday on whether rosiglitazone should stay on the market in Europe. British regulators have already asked that the drug be withdrawn. But delays are possible given still pending decision from the FDA after its own hearing in July.

via medpagetoday.com

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