⚗️ How to Get a Drug Approved, and Hurricane Beryl

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I am currently sitting by a beach in Antigua, bracing to experience the very peripheral coattails of Hurricane Beryl as it advances west through the Caribbean.

Today’s newsletter:

🌀 Why Hurricane Beryl is historic

⚗️ How relationships sit at the center of pharma and biotech

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In Brief: Hurricane Beryl

Bearing down on the islands of the Lesser Antilles in the Caribbean Sea is a category 4 hurricane nicknamed Beryl. It is the first time in the nearly 200 year recorded history of Atlantic storms that a hurricane this powerful has developed in June.

Beryl developed alarmingly fast, moving from a ‘tropical storm’ classification to that of a category 4 hurricane in just 42.5 hours between Friday and Sunday. As it makes landfall on the islands of St. Lucia, Grenada and others, its windspeeds are being recorded as high as 130 mph.

The cause of this early and rapidly formed hurricane is not shockingly, due to the rise in global ocean temperatures. The heating Atlantic ocean has become akin to a pressure cooker, creating an environment where storms may grow faster, and more unpredictably than ever before.

The Atlantic is not the only ocean on earth experiencing these effects. The Bay of Bengal in the north Indian ocean, historically home to some of the most powerful cyclones ever recorded, has similarly seen a rise in cyclone frequency and potency the last two decades.

Our ocean’s cover 70% of the planet, and act as a heat sink, absorbing 90% of the warming earth has experienced in the last few decades. These storms are a direct consequence of that heating.

Relationships in Drug Development

If there is one thing I have learned working a half-decade alongside the life science and biotech space, its that drug development is absurdly complex, difficult, expensive, and highly reliant on who you know. I say this not from the perspective of a scientist, regulator, or investor, but from that of a wily comms guy, so take this all with a grain of salt.

Last week, patients with Duchenne’s, a rare but incredibly debilitating form of muscular dystrophy, saw a shimmer of hope. A new gene therapy called Elevidys, from a company called Sarepta Therapeutics received expanded FDA approval despite missing the mark on the drugs’ primary endpoints (endpoint = main measurable outcome) during its trials.

Gene therapies are without a doubt one of the craziest, wildest, most expensive yet cutting edge innovations humans have ever dreamed up. If you are not familiar, gene therapies involve altering or introducing a new gene to a patient to treat an underlying genetic condition. They are often used as early interventions in young children with rare genetic diseases, as is the case with Duchenne’s.

They are also notoriously hard to research and create. As of January 2024, the U.S. Food and Drug Administration (FDA) has approved 17 gene therapies; the first one only being approved in 2017. These drugs are not cheap to develop, and the total estimated clinical-stage research and development (R&D) costs to bring a new gene therapy to market can cost billions, yet these drugs fail their trials more than 90% of the time.

So if you are in the business of creating one of these drugs, you not only need a lot of fuckin’ money, and a lot of very smart people, but you also definitely need a very strong relationship with the FDA.

Case in point: the reason Sarepta’s gene therapy even received expanded approval is because the head of the FDA’s Center for Biologics Evaluation and Research (CBER) division, Dr. Peter Marks, overruled regulators and made sure it happened.

While Marks’ argument is that approval gives patients with Duchenne’s (which has no cure) the opportunity to try this new gene therapy, many other regulators and industry leaders are raising concerns, claiming Sarepta is receiving what appears to be preferential treatment despite their trials for the drug being rife with lukewarm data.

The Bigger Picture

From the outside looking in, it is easy to see why pharma and biotech gets a bad rap from the general public. Afterall, the pharmaceutical industry spends millions of dollars lobbying the federal government each year, yet patients still see steep costs for accessing these life saving medications, or have to fight through America’s lovely insurance system to seek coverage, all while pharma and biotech bros rake in millions of dollars.

That’s the easy way to look at, but my brief half decade glimpse beneath the curtain reveals a far more complex industry, filled with constant failure but amazing biologic breakthroughs alike. And at its heart sits the FDA.

The FDA has a very very difficult role. They are the ones who ultimately decide if the benefits of a drug outweigh the risks to the general public, while also balancing how approvals influence a highly complex drug development market. In the case of Sarepta, the FDA appears to be at least publicly choosing the possible benefit to patients. The controversy here in part comes from what this means for future gene therapy approvals.

The FDA expects to approve anywhere from 10 to 20 gene therapies annually over the coming years. Will other companies with similar data concerns see the same preferential treatment as Sarepta? Or will the FDA (and more specifically, Peter Marks) defer more closely to its regulatory committees?

Again, whether acknowledged or not, it will likely come down to the relationships the executives of these companies have with the FDA.

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The point of this is not to decry biotech and pharma, or point fingers, but to illustrate the complexity of this industry. After all, these companies are not selling fancy cars, they are in the business of creating life saving therapies that not only cost an absurd amount of money to develop, but fail far more often than they succeed.

If they do succeed, these companies will seek to price their drugs at a point where they can make a profit. For this fast emerging gene therapy space, that price point can range from hundreds of thousands, to millions of dollars for a treatment. Elevidys’ one-time treatment comes with a price tag of $3.2 million.

Again, these treatments are some of the wildest innovations mankind has ever drummed up. A single gene therapy intervention can alter the course of a child’s entire life. But if these companies cannot regularly turn a profit, then they go bankrupt and thus cannot create more life saving drugs.

Is that greed? Or is that just the math of running a business? How does FDA approval of one gene therapy impact the likelihood of the next approval? How does that impact the overall market of drug development? What if a therapy does not end up working in patients? How do patients afford even trying the therapy? Which therapies does the federal government subsidize coverage for consumers through our tax dollars? There are a lot of questions involved, and a melting pot of government regulators, private investors, patients, and researchers who will give you many different answers.

Its a game of incentives, run by humans who by our very nature are flawed organisms. There are those in the game to make a lot of money, and those here to create live saving treatments. There’s a Venn diagram there, and at its center are the relationships in the industry that make everything else move forward.