KTOV: The Legal Cloud Hanging Over the Science

Published: 4/23/2018

Read the article disclaimer first. This article may be updated with important information in the near future. Subscribe to Healthonym’s free newsletter to receive an alert if and when that happens.

Summary

  • KTOV is facing a lawsuit and securities investigation into alleged data fabrication.
    • Even if the NDA is perfect, the FDA may issue a CRL for KIT-302 as a result.
  • The primary efficacy outcome, while successful, has a potential statistical issue.
    • The pivotal trial’s results are also partially contradicted by several independent studies.
  • The NDA might be missing an important substudy.
  • KTOV’s chronic delays may have decreased its chances of approval by a factor of ~2.
  • A lack of a PDUFA extension could be a bad sign.

BACKGROUND

KIT-302 (Consensi) is an oral combination product that contains an NSAID, celecoxib, and a calcium channel blocker, amlodipine. It’s being developed by Kitov Pharmaceuticals (ticker: KTOV), an Israeli company.

KTOV’s NDA for KIT-302 has an expected PDUFA action date of May 31st, 2018.

KIT-302’s main indication will be for the treatment of hypertension in patients who need to take an NSAID to relieve the signs and symptoms of their osteoarthritis as well.

During its clinical studies, KIT-302 wasn’t tested in its final commercial (fixed combination) form. Instead its two active ingredients were given simultaneously, but separately, to mimic the final formulation.

For brevity’s sake, we’ll refer to the test/mimic combination as “KIT-302” when discussing the pivotal trial below.

THE LEGAL PROBLEMS

Before any discussion about the scientific, statistical, and regulatory merits behind KTOV’s NDA can begin, we have to put everything into the context of an existing legal problem.

On 02/06/17, KTOV’s CEO was apparently arrested, questioned, and then released under certain restrictions by the Israel Securities Authority (ISA).

Based on everything we know at this point, it seems there were multiple whistleblowers who might have come forward with information that someone party to the pivotal trial deliberately misled the Data Monitoring Committee (DMC).

By extension, this means investors were misled when KTOV issued numerous positive statements about the trial.

The main accusation is that someone falsified the data to trick the DMC into thinking statistical significance for the co-primary (efficacy) endpoint was reached.

The data that was apparently falsified was the experimental arm’s; where the changes in blood pressure for those treated with “KIT-302” were modified to look better.

POSSIBLE EXPLANATIONS

KTOV denies any and all such accusations. But what are the possibilities?

1. Nothing actually happened.

2. The clinical research organization (CRO) independently falsified the results. This is extremely unlikely but not impossible.

3. Someone pressured the CRO into falsifying the data.

4. The sponsor had access to, or complete control of, the data set. It’s possible then, that the sponsor falsified the data prior to its submission to the DMC. This appears to be the implication in the legal opinion/order.

Of course, lawsuits seeking compensation as a result of a sponsor’s “misleading information” are filed left and right; and are dismissed just as often.

Yet in KTOV’s case this doesn’t appear to be a frivolous lawsuit since it avoided outright dismissal.

That might be because it met a heightened pleading standard; based in part on the numerous whistleblowers who apparently stepped forward.

Above and beyond that, it’s hard to believe that the equivalent of the Israeli SEC would launch, and then continue to investigate for over a year now, something that is completely meritless.

WHAT THE FDA MIGHT DO

Read the article disclaimer.

Last Updated: 5/13/2018 for elements of style.

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

2018-12-05T16:11:44+00:00