Dr. Philip Krause, Former FDA Employee

Two big questions that go unanswered

Recently I watched an interview of Dr. Philip Krause by independent journalist Rav Arora on the Illusion of Consensus Substack.

Dr. Philip Krause is best known for resigning along with Dr. Marion Gruber from the FDA in August 2021. These unexpected “retirements” were striking because Gruber and Krause were the two FDA employees in charge of reviewing the Pfizer/BioNTech mRNA COVID-19 vaccine for use as a booster. This was a blackeye for the agency—having the two seasoned employees charged with reviewing the vaccine resign in the middle of the review.

Krause, Gruber, and others wrote an article in the Lancet in October 2021 that was critical of the FDA for its plan to use the shots as boosters, along with other complaints. In the interview with Arora, Krause stated that the reason he and Gruber resigned from the FDA was the pressure they received from above to promise an approval date. While the vaccine was eventually approved for use as a booster, Krause and Gruber could not in good conscience promise an outcome and a date for that outcome and follow their mandate to evaluate the vaccines properly and fully.

After Gruber and Krause left, the day after the vaccines were approved via an Emergency Use Authorization, on September 22, 2021, the Biden administration pushed for mandating the mRNA shots as boosters. And with those developments, a supposedly scientific agency became a politicized one.

That’s not what I want to cover here, however.

I thoroughly enjoyed listening to Krause and I applaud Arora for asking just a few questions and letting Krause talk at length. Krause did a good job—one of the best I’ve ever heard—of explaining what the FDA does and why. Overall, he provided a good justification of the FDA. After listening to him, one is left with the impression that he more fully embodied the FDA’s vision than the FDA itself. Or, to mirror Ronald Reagan’s explanation for why he left the Democratic party, Krause didn’t leave the FDA, the FDA left Krause.

And yet Krause’s explanations didn’t touch two very big questions that I still have.

The first big question: Why can’t other drugs get EUA approvals?

The FDA has an Emergency Use Authorization (EUA) process for life-saving products that can’t wait for a full FDA review and approval. According to Congressional documents, for an EUA approval, the FDA must think that it is “reasonable to believe” that the product “may be effective” and that the “known and potential benefits of the product outweigh the known and potential risks of the product.”

According to Yale Medicine, “Put simply, an emergency use authorization (EUA) is a tool the Food and Drug Administration (FDA) can use to expedite the availability of medical products, including drugs and vaccines, during a public health emergency. An EUA can only be granted when no adequate, approved, available alternatives exist, and when the known and potential benefits outweigh the potential risks. An EUA also only lasts as long as the public health emergency for which it was declared.”

While we can debate whether these conditions were met for the mRNA COVID vaccines in December 2020, when they were first given an EUA, we should ask why other, fully deserving products, don’t have the same opportunity to take advantage of the EUA approval pathway.

Consider LAD-I, which is a rare genetic disorder affecting the immune system. With this condition, white blood cells are unable to leave the bloodstream and move to the site of an infection. As a result, patients with severe LAD-I cannot fight life-threatening infections. Without a successful bone marrow transplant, severe LAD-I is fatal during the first two years of life—at age five months, on average. Unfortunately, bone marrow transplantation is a difficult and risky procedure that is possible in only about 25% of cases. Stated differently, for 75% of kids, this is a death sentence.

If babies are dying and no good treatments exist, doesn’t this qualify as a health emergency?

Enter a gene therapy treatment, called Kresladi, from Rocket Pharma. Kresladi has been tested in a small clinical trial and from what I understand the treated patients are doing very well. Note that with such an exceptionally rare disease, a small clinical trial is all that’s possible. Kresladi is a one-and-done treatment that corrects the underlying genetic deficiency.

The problem? Kresladi has been held up for a year at the FDA for what appears to be a staffing problem. This additional year is subsequent to the date the FDA was obligated to provide a clear yes or no response to Rocket about Kresladi. Rocket is still waiting for an FDA approval of Kresladi.

Let’s make this clear. Babies with severe LAD-I can survive for at most two years. A quarter of these babies can get a difficult and problematic therapy while three-quarters can’t. There’s a treatment for which it is “reasonable to believe” “may be effective” and the “known and potential benefits of the product outweigh the known and potential risks of the product.” This isn’t a difficult comparison. Death outweighs the potential risks of treatment with Kresladi.

If you had a baby suffering from LAD-I, would you rather watch your child die or would you rather try a gene therapy that has been successfully used by nine other babies in a rigorous clinical trial? The answer seems pretty obvious for the cases I can imagine.

The families of babies with LAD-I deserve an EUA for Kresladi. Now in a year or two. Not in six months. Tomorrow.

The second big question: Why do drugs need full FDA approvals?

Based on the way the mRNA COVID-19 vaccines were approved, approximately 160 million Americans received them before they were fully evaluated by the FDA. That 160 million figure refers to people who got the shots after the EUA but before the full approval. Another author referenced 363 million doses of the mRNA COVID-19 vaccines being administered before the full approval, which is another way to look at it.

Further, the manufacturing facilities for these mRNA COVID-19 vaccines were never inspected by the FDA before full approval, even though one of the companies—Moderna—had never produced a single commercial drug or vaccine in its entire history and no companies had ever produced commercial mRNA products. This was a completely new approach to developing drugs.

In other words, the FDA said it’s okay with Americans receiving drugs that hadn’t been fully evaluated by the FDA. If that is true, why does any drug ever need to be fully evaluated by the FDA? Why can’t all approvals be simpler EUA-type approvals?

Such a solution conforms with the FDA’s mission. According to the FDA’s website:

FDA is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health.

Drug development is an expensive and lengthy process. This one simple change would provide Americans with life-saving and live-improving medicines faster and more cheaply, objectives which dovetail with the FDA’s mission.

Dr. Philip Krause, do you have answers to these two big questions? If so, I would love to hear your thoughtful responses.