Aethlon Medical Inc (AEMD)

[ANESRI]

http://www.medpagetoday.com/InfectiousDisease/Hepatitis/26136

I have highlighted some interesting points which may work out in AEMD's favor.

However, a briefing document released in advance of the meeting did raise concerns about skin rashes and anemia seen in patients receiving telaprevir in clinical studies and the emergence of mutations in the drug's enzyme target that appear to render the virus drug-resistant.


Sustained response rates were lower in patients with previous inadequate responses to the standard treatment, but still much higher than in control groups receiving another round of conventional therapy:

Prior null responders: 31% versus 3%
Prior partial responders: 57% versus 15%
Prior relapsers: 84% versus 24%
Relapse rates were slashed in patients receiving telaprevir relative to controls: 5% versus 26% in previously untreated patients and 10% versus 57% in treatment-experienced patients.

The core dosing recommendation proposed by Vertex for the drug's label is 750 mg of telaprevir three times daily for 12 weeks, combined with peginterferon and ribavirin at standard doses for 24 or 48 weeks, depending on virologic response.

For treatment-naive patients and prior relapsers whose viral loads are undetectable at weeks four and 12, the shorter regimen would be recommended, according to Vertex's application. Other patients would receive the full 48 weeks of therapy.

This type of "response-guided therapy" raised a concern for FDA staff reviewing the data for boceprevir, as some of the trials showed lower response rates for the alternative dosing scheme.

The FDA's briefing document for telaprevir, on the other hand, did not highlight any problems with the response-guided therapy, although the advisory committee will still be asked to consider its appropriateness.

A somewhat greater worry for FDA staff was a finding of mutations in the HCV protease enzyme that appeared to make the virus resistant to telaprevir. Data from the trials indicated that, in patients not maintaining good responses, certain point mutations in the protease had emerged during treatment.

In one of the studies, 90% of treatment failures had treatment-emergent amino acid substitutions in the protease sequence, according to the briefing document.

The significance of this treatment-emergent resistance also will be a topic of discussion for the panel.

Safety concerns center on two toxicities seen during the telaprevir studies -- skin rashes that, in some patients, were severe enough to warrant stopping the drug, and anemia that was substantially more common with telaprevir.

More than half of patients receiving the drug reported rash or pruritus, with 6% discontinuing treatment as a result. These rates were about double those in the control groups.

Similarly, hemoglobin reductions of grade 3 or more were seen in 55% of telaprevir patients versus 25% of control patients.

Anemia is also an issue for boceprevir, but the skin problems are unique to telaprevir.

Advisory committee members will be asked how these side effects affect their risk-benefit assessments.

Other discussion topics will include recommendations for telaprevir's use in specific populations such as blacks -- as with boceprevir, sustained response rates were about 20 percentage points lower in African Americans -- and recommendations for postmarketing studies on the drug's optimal use.