The Scientific Issues Surrounding ZTlido’s Upcoming PDUFA Date

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BACKGROUND WISDOM

ZTlido is the trade name for a patch containing lidocaine 1.8%. The trade name stands for the ‘Z’ero H20 ‘T’transdermal ‘Lido’caine Patch.

The active ingredient in this patch, lidocaine, is a drug that’s often used as an anesthetic/pain reliever. The percentage (1.8%) signifies there is 18 milligrams (mg) of lidocaine for every gram of adhesive material in this patch; with the adhesive material being the substance within which the lidocaine is suspended.

As such, ZTlido is indicated for the treatment of postherpetic neuralgia. This is nerve pain as a result of shingles (aka herpes zoster), a condition caused by the varicella-zoster virus. This virus also leads to the more familiar chickenpox.

Once applied to the body, the lidocaine in this patch passes through the outermost layer of the skin. After doing so, it acts on nearby damaged nerves and minimizes their ability to transmit, or start the transmission of, pain signals to the brain.

PATCH PROPERTIES

ZTlido is a very thin, single-layer, and flexible patch (a benefit to patients applying it on contoured areas of the body). The patch also uses what’s known as hot-melt, pressure-sensitive adhesives. In short, these are substances that can form a sticky and effective bond with the skin upon the application of light pressure.

Furthermore, ZTlido is an anhydrous patch. In other words, its formulation doesn’t need water, helping to minimize the costs of manufacture as a result.

ZTLIDO VS. LIDODERM

ZTlido is meant to be a competitive, improved, yet bioequivalent answer to Endo Pharmaceutical’s Lidoderm, a lidocaine 5% patch indicated for the same purpose as ZTlido.

When compared to Lidoderm, ZTlido is marketed as improving patient compliance (proper use of the medication), decreasing environmental waste, and improving the safety of children and pets.

How so?

Lidoderm contains 700 mg of lidocaine in each patch but only 1%-5% of it is ever absorbed by a person’s body. This means that upwards of 99% (693 mg) of the medication remains unused and is thrown out, needlessly increasing environmental waste and contamination.

Furthermore, ZTlido is engineered to stick to a person’s body even during moderate exercise, helping to improve patient compliance by decreasing the chances the patch will fall off and need replacement.

In contrast to Lidoderm, each ZTlido patch contains only 36 mg of lidocaine. While this seems like a relatively small amount, ZTlido’s manufacturer claims the drug is delivered more effectively than Lidoderm, minimizing the amount of lidocaine needed per patch.

This also means that if a ZTlido patch falls off accidentally, a child or pet who comes into contact with the patch will be exposed to a relatively low amount of lidocaine when compared to Lidoderm. The smaller amounts of lidocaine per patch may help reduce the potential for side-effects as well.

As a result of novel adhesive and delivery mechanisms, ZTlido is a patch that weighs less than, and is half as thick as, a Lidoderm patch.

NDA TIMELINE; SCILEX & SORRENTO

ZTlido’s initial NDA was submitted to the FDA in mid-2015 by Scilex Pharmaceuticals. In May of 2016, Scilex received a complete response letter (CRL) and thus their application was rejected for numerous reasons outlined in the next section.

In August of 2016, Scilex met with the FDA to discuss the CRL and, thereafter, believed it would be able to resubmit their NDA relatively quickly, expecting an FDA action date in mid-to-late 2017.

By late 2016 Scilex was acquired by Sorrento Therapeutics (Ticker: SRNE). The former resubmitted their NDA for ZTlido in late August of 2017 with an expected PDUFA action date of February 28th, 2018.

WHY DID THE FDA REJECT ZTLIDO?

As per the CRL, the FDA mentioned the need for at least the following upon re-submission of the NDA:

  • A new pharmacokinetic (PK) study was requested. PK refers to the ways by which the body absorbs, distributes, metabolizes (chemically changes), and eliminates the drug. In short, Scilex was requested to show what the body does to the drug with a new study.
  • A new 3-month-long animal study analyzing the drug’s toxicity. It’s not explicitly clear if this was recommended or actually required by the FDA.
  • The need to address several issues related to quality assurance.

We go over these in order but do be aware that these are the problems we know about overtly and other issues are, of course, possible.

A NEW PHARMACOKINETIC (PK) STUDY

The FDA requested a PK study to help determine if  ZTlido and Lidoderm are bioequivalent or not.

Scilex completed the additionally requested PK study and announced its results at the end of 2016. The company mentioned that a primary endpoint and a secondary endpoint were met.

They were likely referring to the following two PK/bioequivalence endpoints:

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Published: 2/13/2018

Updated on: 2/15/2018 – the article’s content was not altered; only the article disclaimer was modified on this date.

No one associated with this article has any financial stake in, or ties to, SRNE.

2018-12-05T16:12:55+00:00