FDA says NO again to Serono's second try to get Serostim approved for lipodystro

[Guest guest]

From Tim Horn, a well known activist friend

I just wanted to report back from yesterday’s Type C meeting between the FDA and EMD Serono at the agency’s new, sprawling White Oak campus in Silver Spring, MD. To refresh memories, the meeting was requested by Serono to discuss the July decision by the agency to withhold approval of Serostim for HARS (visceral fat gains).Prior to the meeting, Serono submitted an amended sNDA in an effort to address some of FDA’s lingering concerns. In the original application, Serono requested approval at a 4 mg daily dose for 12-week induction therapy (followed by alternate-day dosing for maintenance therapy). However, the risk of hyperglycemia and diabetes was noteworthy using this dose in the two Phase III studies completed to date. As a concession, Serono’s revised sNDA requested approval at a dose of 4 mg every-other-day. While the FDA conceded that alternate-day dosing appeared to be associated with a lower risk of hyperglycemia and diabetes, this dose – as induction treatment – was only explored in one of the two studies. In other words, there simply isn’t enough data exploring the safety and efficacy of Serostim 4 mg QOD to support approval. According to Parks, director of the agency’s endocrinology division, “the data show proof-of-concept using a 4 mg alternate-day dose; they cannot be considered conclusive with respect to drug approval.†Serono also made a commitment to the FDA – the production of a “risk management program,†including clinician training and a need for baseline and follow-up glucose tolerance testing. Dr. Parks said that this is commendable, but “in itself does not strengthen the approval application.†FDA acknowledged that it does not expect a drug to have a durable VAT effect after it is discontinued. As long-term therapy will ultimately be needed, the agency is requesting additional data from Serono exploring the durable safety and efficacy of Serostim when used for at least six months. Currently, Serono only has 12 weeks of treatment, followed by another 12 to 24 weeks of maintenance therapy, in their data set, which does not satisfy the FDA’s durability requirement. With respect to Serono’s claim that VAT reductions associated with Serostim therapy should be considered a surrogate marker of improved cardiovascular health, Dr. Parks stressed that the risk of hyperglycemia and diabetes must also be considered to be a surrogate marker in this regard. She said, “I don’t see the benefit of improving one *potential* marker of cardiovascular disease at the expense of increasing the risk of another *known* marker of cardiovascular disease [diabetes].â€In short, Serostim will not be approved for HARS. It may be approved – and it sounds like a big “if†– upon successful completion of another Phase III study exploring six months of 4 mg QOD therapy, compared with placebo, that included evaluable risk management program components. Dr. Parks told Serono, “by the time another study is completed and presented for review, another drug with comparable efficacy and a better safety profile will have been approved†– a favorable acknowledgement of Theratechnologies’ tesamorelin quest for the same indication. Parks addressed our ATAC letter on several occasions and agrees that Serono should consider incorporating nutritional and exercise components, to maximize treatment durability and sustainability, in another Phase III study of the drug. At this stage of the game, I have no idea if Serono is planning on moving forward with its HARS research program. I think they’d be foolish to do so. They have effectively lost their one advantage over tesamorelin – a brief marketing and sales window. I think we’re at the end of the line here. Tim Horn

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