PCSK9 Inhibitors: What Can They Do for the 29 Million Americans With Diabetes?

By Kelly Close

Twitter Summary: @kellyclose speaks to @US_FDA in favor of PCSK9 inhibitor drug Praluent – need to bring more options to #PWD to fight against CV disease

Update: The FDA Endocrinology and Metabolism Drugs Advisory Committee (EMDAC) voted 13-3 in favor of Praluent (alirocumab) for "at least one patient population." Note, while this vote does not mean that the drug is approved, it provides hope that it will likely be approved for at least a subset of patients, particularly those with specific genetic backgrounds.

The following day, EMDAC voted 15-0 in favor of Amgen's PCSK9 inhibitor Repatha (evolocumab) for those with homozygous familial hypercholesterolemia. They also voted 11-4 in favor of Repatha for at least one or more other patient population(s).

Original Article:

Today, I spoke to the FDA about an exciting new drug class that lowers LDL cholesterol (the "bad" kind) – its approval would provide an additional option to statins, the long-standing “gold standard” that has left many of us patients with inadequate cholesterol control. Millions of people with diabetes understand too well the difficulties of cholesterol management, as cardiovascular disease (CVD) remains the number one cause of death in people with this disease.

I spoke to the FDA, because as a patient I want to make sure that health care providers have more tools to help us manage heart disease. This new drug class – called PCSK9 inhibitors – has had tremendously impressive clinical trial data. Just this past weekend, we heard at the ADA how these drugs can reduce LDL cholesterol levels by 60% with no adverse effects for people with type 2 diabetes already on statins. More information about these drugs can be found here.

Stay tuned for the outcome of this meeting, which will determine whether or not the FDA Advisory Committee will vote in recommendation or against recommendation for this drug (specifically – today’s meeting is about Sanofi’s Praluent, aka alirocumab. Amgen has an Advisory Committee meeting for its own PCSK9 inhibitor drug tomorrow). For now, my full remarks to the FDA can be found below.

My Speech to the FDA in Favor of PCSK9 LDL Cholesterol Lowering Drugs

Good afternoon, I’m Kelly Close, the founder of The diaTribe Foundation, which works on improving life for people with diabetes and prediabetes – I’ve had diabetes nearly 30 years. Today, I want to discuss the huge potential of PCSK9 inhibitors for people with diabetes.

Cardiovascular (CV) disease is the leading cause of death for people with diabetes, and it has become increasingly clear that effective prevention requires a holistic approach that addresses a bunch of risk factors – LDL is a big one, and others include blood pressure, glycemia, mental health, and other problems that impact adherence, which is a problem with many drugs, even statins.

We know for people with diabetes that lipid management, and LDL lowering in particular, MUST be better addressed. We’ve heard from plenty of leaders in diabetes and cardiology that managing cholesterol is THE most important thing people with diabetes can do for their CV health.

And, is this happening?

We’ve seen a bunch of curves over time on how we’re doing on CVD health in the US overall, and it’s nothing to write home about anymore, especially as diabetes expands at such crisis proportions and as CVD in people with diabetes is SO rampant and affects those broad population CV curves so negatively.

Despite some significant progress over time, many people with diabetes have trouble meeting their LDL goals, and there is a significant need for new therapies that are easy to use and ones that work well for those that don’t have other options. According to NHANES, only 56% of people with diabetes with an LDL target of 100 and only 28% of people with diabetes with a target of 70 achieved their goals.

How do we feel about how patients with diabetes are doing currently with regard to CV health?

As diabetes and CVD both hit lower ends of the socioeconomic spectrum, please consider how you could help by making better CV therapies available. For a marginalized group, this would be really welcome – especially as 20% of them can’t even take statins. 20% may sound low, but that’s 6 million people with diabetes alone. Now, this would be an intervention on a large scale that could have truly far reaching implications.

From a patient perspective, I’d love to see an ecosystem in which:

• Outstanding therapies can be developed and approved.

• Commercial markets can emerge, putting funds back into R&D and patient support.

• Sensible reimbursement, including CMS coverage, can happen.

• Therapies eventually go generic and can reach EVERYONE, especially people with lower income levels.

It is incredibly important from a public health perspective to get therapies out more broadly that work better without so much work from doctors, so many heart attacks and strokes, and so many hospital costs – we spent $250 billion last year on diabetes in the US alone and so much of that was due to preventable CV events.

Some of the data shown today – we’d kill for this in diabetes therapies.

Data from ODYSSEY LONG TERM presented just over the weekend at the ADA showed LDL reductions of close to 60% and no significant increase in adverse events with alirocumab on top of statin therapy in people with type 2 diabetes, which was comparable to the results in patients without diabetes. In diabetes, that’s like getting to a 5.5% or 6% A1c safely with no hypo, weight gain, edema, bone weakness, association with congestive heart failure, etc.!

To sum up, the 29 million people with diabetes in the US need more options to manage CV risk, and PCSK9 inhibitors offer an unusually compelling risk/benefit profile. While we of course look forward to seeing data from the ongoing CV outcome trials, we believe there is already a strong body of evidence to support a broad approval.

We at diaTribe hope you can consider doing something deliberate on the diabetes side and making a statement about wanting to help people with diabetes, and wanting to help us NOW. Let the patients and their healthcare teams on the front lines figure out how much risk they want to take on.

There is SO much we need to do for people with diabetes – let’s at least start with what works. As a multi-disciplinary group, you could think together about how taking an even more active stand about how directly addressing CVD in people with diabetes can make a difference to the overall CV health of the US. We know this works. There is a crisis on our hands in diabetes. Act. Please do something your public can be particularly proud of, and put FDA and EMDAC as a leader among leaders in moving forward better alternatives for people to fight cardiovascular disease.