What is GSK Thinking With Its Latest NDA?

An FDA reviewer said that Promacta, an experimental platelet-boosting drug seeking an indication for acute treatment of chronic idiopathic thrombocytopenia purpura from (GSK), did not help control bleeding any better than a placebo. The reviewer wrote:

The data provided in this NDA (new drug application) do not demonstrate statistically significant, robust … treatment effect in decreasing bleeding events,

The FDA is already being stingy about approving NDAs when they demonstrate statistically significant effects. I can’t imagine the advisory board, which meets Friday, is going to issue a positive opinion about recommending an acute therapy for a chronic disease state, especially with non-statistically significant results.

I’m not a regulatory guy, so anyone want to explain the GSK reasoning to me?

Comments

[RoccoVerducci]

Eben,

It might be prudent to examine the total body of clinical work before rendering a negative opinion on Promacta or GSK. The FDA's outside advisory board of learned clinicians opined a positive outlook about Promacta with respect to ITP. Historically, the FDA follows the guidance of the advisory board.

Sincerely,

[Eben Tessari]

Right... but I don't, nor does anyone outside the committee have access to the application. GKS and Ligand's stock dropped quite a bit on wednesday after the news. I wasn't the only one making assumptions.

I was proffering opinion on comments by member of said committee and was asking anyone who has more regulatory experience than I, to comment and enlighten me.

Waiting until the meeting has concluded and using their positive opinion still doesn't answer the question I asked. Do you have any insight to add or do you just chide those with an opinion?

[Eben Tessari]

Right... but I don't, nor does anyone outside the committee have access to the application. GKS and Ligand's stock dropped quite a bit on wednesday after the news. I wasn't the only one making assumptions.

I was proffering opinion on comments by member of said committee and was asking anyone who has more regulatory experience than I, to comment and enlighten me.

Waiting until the meeting has concluded and using their positive opinion still doesn't answer the question I asked. Do you have any insight to add or do you just chide those with an opinion?

[RoccoVerducci]

Eben,

Please accept my apologies if you inferred that I was chiding you. That was not my intent. I supply the additional information as an FYI.

ITP can be divided into two different forms

• Acute ITP starts suddenly and usually follows a viral illness in a child. Acute ITP may require no treatment, especially if the platelet count does not fall too low and there is little bleeding. It usually improves spontaneously and, in children at least, rarely comes back.*

• Chronic ITP develops over time, is long lasting and more common in adults. It may not need treatment if the platelet level doesn't pose a significant risk of -bleeding. *

Both are treated similarly. However in the chronic setting if the platelets fall dramatically, then a product with the promise of a Promacta may help restore platelets to a medically acceptable level. There are a wide range of medical conditions where thrombocytopenia may be a critical concern (e.g. intracranial hemorrhage) or it may be a medical state that precludes the use of life-saving drugs (e.g. chemotherapy, interferon therapy or antiviral therapy) for disease entities such as cancer, HIV and Hepatitis. Theoretically, if a pharmaceutical were to have the properties of remarkably stimulating platelet synthesis, then it may allow the critical use of life-saving drugs in a patient population whose low platelet count (in the past) has been an exclusion criterion.
The vying for a “chronic” indication for ITP would not be plausible from an indication perspective since it would necessitate the need to have long-term studies completed at the time that the NDA was filed. Additionally, this would delay any potential use of a product in a patient population that has a bona fide need for its therapeutic benefit today. What may be more achievable is to have application for the “episodic” or “acute” aspect of a chronic condition. This may very well be the rationale for the drug that you have inquired about.

As to your question as to the rationale for an “acute” medication treating a “chronic” condition; this paradigm of use is no different from how asthma is medically managed. People with asthma use pharmaceuticals to control inflammation and vasoconstriction which are part of their chronic state. However, when they have an acute attack, they augment their management of asthma with a rescue inhaler (albuterol). As valuable as their rescue inhalers are, they are intended to be used only when there is an acute attack of their chronic condition.

In any event, if you add 98 cents to the aforementioned, you should have one dollar.

Ciao,

• footnote - www.netdoctor.co.uk/di...
• P.S. I enjoy reading your column.

[Eben Tessari]

Rocc,
Took me to school. Best comment ever. Period. Thanks for reading.