FDA EMDAC Public Comments

I had the privilege of offering public comments at the December 12 FDA Advisory Committee meeting for BMS/AZ's dapagliflozin (aka DAPA). My comments were roughly what follows. I say roughly because I know I get lost and stray from the notes. I have tried to bring what portions of my ad-libbing I remember into what follows.

My sincerest thanks to Kelly Close and the team at diaTribe for sharing detailed background material that made it possible to offer informed comments. DAPA has had a complex and carefully scrutinized regulatory path. There were concerning possible signals of risk. Without being able to read though its history it would have been impossible to appreciate the Sponsor's (FDA hearing speak for the pharma companies behind the drug application), FDA's and committee's conversation on those risks. 

My Comments:

Good afternoon. My name is Bennet Dunlap. I have no relationship with the sponsor. My travel here today is at my own expense, including the cost to a good nights sleep of getting up at 4:am to drive down from Philly for this meeting. 

I am a diabetes advocate, a blogger, been a PCORI reviewer and I recently created the StripSafely.com campaign for meter accuracy. I am a member of Diabetes Advocates, an association of diabetes patients and writers. Last time I was here I absolutely slaughtered the name of the drug in question, so this time I’m not even going to try.

Like 26 million other Americans, I live with diabetes. This morning somebody spoke of unintended wisdom. Those of us with diabetes will take wisdom any which way we can.

I often feel that, the conventional wisdom in medical literature projects that diabetes care is easy. Many of us have felt it is not.  We have found  it doesn’t help when – despite our best efforts – we are labeled non-compliant.  Maybe the problem has to do with unrealistic expectations, or maybe the problem has to do with imperfect treatments.

What I am certain about is while all of us with diabetes can benefit from similar diet and exercise, there is no one size fits all approach to good diabetes medications. We need choices to talk about with people like Bob Ratner, (Gesture to Bob who just spoke) our doctors…  and we need innovation.

Which brings me to the purpose of today’s meeting.

Has the sponsor met the safety and efficacy requirements to market their candidate drug and does it present potential heal value to some of us living with diabetes?             

Broadly speaking, the class of SGLT medication is an exciting new opportunity for glucose regulation. The class encompasses four benefits we haven’t seen together before in one diabetes therapy:

- improved glucose, 

- weight loss, 

- less hypoglycemia, 

- and ease of use that comes with a pill. 

Expanding the class with this DAPA increases choice: although there is already one approved for SGLT-2 therapy, a second one would provide obvious benefits from competition, broader education and outreach. 

We all know third party payers love to bid the pharma. companies against each other and a second SGLT-2 would give them a chance to do so in this exciting new class.

As you consider benefits of diabetes medication outcomes, I encourage you to look to endpoints that can create success in patients’ daily lives. In addition to endpoints of lowering A1C, and avoiding cancer and CV risk profiles -  look to endpoints that we can see and feel in our daily efforts to be “compliant.” Medicines that show less weight gain or even loss and less hypoglycemia can help with the phyco-social struggle to stay compliment. 

The safety issues raised at the DAPA first hearing we're quite concerning. Nobody wants to trade blood sugar control for cancer. I appreciate the scrutiny the the agency and sponsor have given to the issues. I was particularly interested in this mornings presentation on the bladder cancer risk and look forward to detailed professional exploration of it this afternoon. 

As Dr Wilding pointed out this morning, we need better treatments. As a patient I worry that regulation creep may inhibit those innovation. That the endpoints move after trials have begun. What constitutes an effective study need to be resolved before the trials start, not after the fact in discussion at an advisory meeting. 

In closing, please remember diabetes care… is self-care. As patients, we see our doctors just a few times a year, maybe for a combined total of an hour, or two if we are really lucky. That leaves us on our own, responsible for self-care the other eight thousand, seven hundred, fifty eight hours a year. 

We could use a hand seeing success in that.  

Thank you very much.

FDA, SLGT-2, EMDAC, T2D & DOC - Alphabet Soup

Last week I had the privilege of giving public comments at a FDA hearing of a proposed new type 2 drug in the class know as SLGT-2. These FDA meetings go by abbreviation EMDAC. So I was the DOC's, T2D, SLGT-2, FDA, ENDAC guy - Stick that in your soup bowl.

The drug in question is a new means of treating T2D. Instead of influencing insulin production or sensitivity, it prevents the kidneys from transporting glucose out of the urinary process, This recovery of glucose conserves energy in the body. DiaTribe has a nice little summary of the specific drug with links to more of their excellent and detailed reporting. If you prefer smaller bites of information here is a twitter search: https://twitter.com/search?q=Canagliflozin&src=typd.

Probably for most of the millenniums that humans have been around this conservation of energy was an important evolutionary advantage.  Not so much today.

By inhibiting this retention of glucose, patients on the medication excrete something like 100 to 300 calories of sugar a day. BG decreases. Significantly it only seems to happen at elevated BD levels.  When BG is in range the SLGT-2 isn't facilitating the excretion of BG or so I understood the presentation.

Readers digest version: SLGT-2s helps T2Ds pee out excessive sugar but doesn't make'm go low.

This may have a beneficial impact on weight. There are of course issues and the increase sugar in the urinary tract causes some increase in infections. YDMV.

There hearings follow a set agenda:

• The committee listens to at the drug sponsor's presentation (sponsor = company seeking approval.) 
• The FDA responds with a presentation of their review.  
• The committee then ask both a bunch of questions. 
• Most of the committee are physicians but there is one patient representative. 
• (The patient representative, at both the EMDAC sessions I attened, was fantastic. She did all patients proud. )
• The public chimes in after lunch. 
• The committee considers specific questions. 
• The committee votes a recommendation to the FDA.

This hearing had 5 people offering public comments, 2 were from the Diabetes Advocates, Kelly Close and myself. One was from the ADA, one was from the American Association of Clinical Endocrinologists. Finally one was with with a public interest group he helped start with Ralph Nader. (See my friend Scott Strumello's comment for more details, Thanks Scott for offering them.)With the exception of the public interest group affiliate, the public comments were about the need for drugs that get used, don't induce hypos and that while no drug is right for everyone, diabetes patients need options to consider with their health team.

I had the privilege of going last - batting clean up as it were. I tried to be slightly humorous with my inability to pronounce Canagliflozin to put an real world  face on the potential patient users of this drug who probably can't pronounce it either. I tried to be clear that I was there as a member of an e-patient and advocacy group. This to suggest that there are possibly a lot of us who may benefit from the drug, even if we cant pronounce it. I spoke about my family history with different Type 2 medications programs to also suggest that probably there is a bunch of us T2D for who it may not be the best choice. Either way that is a choice to make individually with one's physician,

My comments were influenced by listening to the sponsor and FDA presentation and my fellow public speakers. I mentioned Kelly Close by name and twice emphasized her points. 1) there are not enough diabetes specialist, as it took me 6 month to get an endo. appt. to confirm my T2D diagnosis and 2) we need drugs that people take, that work. I the speakers from the ADA and AACE about the fear of hypos that cause some patients to not take their all their meds. I mentioned that even those of us who know better may reduce our meds to avoid hypos, noting that a physician presenting in the morning said he himself did so and implied what do they expect form us civilians?

Both the patient representative on the committee and a member of the sponsor's team approached Kelly and I after the close of the meeting. They thanked us for our comments.  Which was very kind.

The room is a wee tad intimidating. I certainly don't yet feel totally comfortable speaking there. I will keep going and will become better at presenting there. I hope that other patients advocates continue to share views and I am happy to chat with anyone interested doing so at future sessions.

Alphabet soup helps.