Paratek ($PRTK)’s Success Hinges on Oral-Only Trial for Omadacycline; Odds Look Good

As you probably know, the effectiveness of traditional “broad-spectrum” antibiotics has taken a sharp nosedive in the last decade. The widespread prescription and use of these drugs has led to a huge rise in the number of antibiotic-resistant bacteria, leaving manufacturers and researchers scrambling to formulate new versions of old medicine.

Paratek Pharmaceuticals ($PRTK) is one of these manufacturers. Their drug omadacycline is a chemical modification of an old class of antibiotics that hopes to overcome bacterial resistance.

Omadacycline has two successful phase 3 trials already on the books – once for acute bacterial skin infections (known as ‘ABSSSI’ and often caused by the poster child of antibiotic-resistant bacteria, MRSA) and once for community-acquired bacterial pneumonia (CABP). The methods, conclusions, and safety profiles of these studies all look fine, and the study design received a Special Protocol Assessment from the FDA – meaning that the FDA believes the design of the studies sufficient to warrant a new drug application. This is all good news, so why hasn’t PRTK submitted the new drug application yet?

Both of the trials of omadacycline started with an intravenous (IV) version of the drug. This is a problem because by far, the biggest commercial potential lies in oral-only antibiotics. Intuitively, this makes sense – an oral antibiotic can be prescribed and taken at home, while IV drugs require a hospital stay or expensive nursing care. Paratek, of course, is well aware of this, so a few years ago PRTK launched a third phase 3 trial testing an oral-only version of omadacycline.

The success of drug overall will, to a great degree, depend on how good the oral-only data look – data which will probably be presented sometime in the next few months.

The Study

The phase 3 trial for oral-only omadacycline is essentially an exact repeat of the IV + oral omadacycline trial which was already approved. The trials are treating the same disease and have the same “success” conditions.

Because the trials are nearly identical and the IV + Oral trial already received approval, I’m not going to look at the study design too closely for this article. The key question is this: will the oral version of the drug work as well as the IV version?

First, a fairly intricate pharmacokinetics study found that the 300mg oral dose is nearly exactly equivalent to a 100mg IV dose. That does come with a slight caveat, however: the great advantage of oral antibiotics is that they can be taken at home. This is also, of course, the great disadvantage of oral antibiotics – there’s nobody around to make sure you take them correctly. A study found that taking food with omadacycline significantly decreased the amount of the drug that went into the body. With this oral-only phase 3 design, there is a much higher risk of patients not following the protocol, which could result in the drug appearing not to work. I don’t think it’s a likely outcome, but I wanted to note it here.

I searched the previously published studies to see if any had segregated their data between IV patients and patients who had been transitioned to oral omadacycline. As far as I could tell, the only study with separate data was one of the phase 2 studies which had happened to segregate the data because they were looking at the first 72 hours of response. In that study, about a third of patients had switched to oral-only omadacycline within the first 72 hours of the study, and 96% of those patients had seen a clinical significant treatment response. That isn’t a perfect benchmark to use to evaluate the effectiveness, but it will have to be good enough.

The answer to the key question, then is yes. Previous antibiotics have been successful in moving from IV-oriented treatments to oral-oriented treatments; the oral dose appears to be equivalent to the IV dose (as long as people follow the protocol); and some fragmentary data from a phase 2 study appears to suggest that the oral drugs work effectively.

What next?

Assuming I am correct and the phase 3 trial for oral-only omadacycline is successful, expect to see Paratek submit a new drug application (NDA) before the end of 2017. Again, assuming I’m correct about omadacycline, I am confident that the NDA will be approved.

I think that $PRTK is a buy.

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Prediction: Phase 3 Approval

The oral version of omadacycline appears to work just as well as the IV version, and since the trials are functionally identical, I expect that oral omadacycline will receive a “go” just like the IV + oral version did.