Keeping perspective

[biopearl123]

As we get close to anticipated approval it is worth remembering just how big an achievement Imetelstat is. Recall that the current LR/MDS study only took patients at the end of the line re treatment options with very high transfusion requirements. It’s worth asking what the 1 yr TI rates would look like if Geron had focused on patients with only a 1 or 2 unit/8week transfusion requirement. But they didn’t. I suspect the “success” rates would have been much higher if they had. In the MF study again, the worst of the worst with the most advanced disease and who experienced other treatment failures. Again what if front line therapy had been looked at. Again with AML. Only the treatment failures with advanced disease. So when the 8 week, 24 week and 1 year (and beyond) data is looked at remember where those patients started: way in the back of the marathon pack. Way in the back. Further back than any other available treatments to date. And look where they are finishing. Pretty impressive if you ask me.

[Ryan]

Loving the recap. Got nothing left to do but count on my fingers and toes anyway.

I would point out enrolling at lower end of transfusion spectrum would have been risky, the placebo effect would have been a lot higher (as you pointed out some time ago which I thought was insightful… patients could be using willpower to hold off on transfusions)… the comparison to placebo is ridiculously (for lack of a better word) good in the MDS trial.

[lacour_98]

I think it was also BP that pointed out some time ago, the placebo patients are receiving the best possible medical care by just being in the trial, medical care they likely would not receive otherwise.

[Ryan]

Well it's been 9 and 1/2 months since the FDA designated the PDUFA date.

Here is what ChatGPT had to offer when I asked about an early decision


You
Give me examples of when the fda made an approval 2 weeks before pdufa date

ChatGPT

The FDA occasionally approves drugs ahead of their Prescription Drug User Fee Act (PDUFA) dates, but it's less common. PDUFA dates are typically set based on the FDA's review timeline and are meant to provide a target date for the agency to complete its review of a drug application. However, there have been instances when approvals occurred earlier. Here are a couple of examples:

Spinraza (nusinersen): In December 2016, the FDA approved Spinraza, a drug used to treat spinal muscular atrophy (SMA), two months ahead of its PDUFA date. The early approval was based on promising clinical trial results showing significant improvement in motor function among infants with SMA.

Tecfidera (dimethyl fumarate): In March 2013, the FDA approved Tecfidera for the treatment of multiple sclerosis (MS), a month ahead of its PDUFA date. This approval came after clinical trials demonstrated the drug's efficacy in reducing relapse rates and disease progression in patients with MS.

These are just a couple of examples, but they illustrate that early approvals can happen, typically when the FDA deems the evidence provided in the drug application to be compelling and the benefits outweigh the risks.

You
Any other examples of a decision even one or more days before PDUFA date?

ChatGPT
While it's less common for the FDA to make decisions just one or more days before the PDUFA date, there have been instances where approvals occurred very close to the scheduled date. Here are a couple of examples:

Vyleesi (bremelanotide): In June 2019, the FDA approved Vyleesi, a drug for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women, just one day before its PDUFA date. The approval was based on clinical trials demonstrating an increase in sexual desire and a reduction in distress associated with low sexual desire.

Doptelet (avatrombopag): In May 2018, the FDA approved Doptelet for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a medical or dental procedure. The decision was made just a few days before the PDUFA date.

While these examples might not be exactly one day before the PDUFA date, they demonstrate instances where the FDA made decisions very close to the scheduled review deadline.

[Ryan]

And, of course even ChatGPT AI could not unravel the intricacies of the FDA to supply this:

What % of the time does the FDA make the decision exactly on the PDUFA date?

ChatGPT
It's difficult to provide an exact percentage of the time the FDA makes decisions exactly on the PDUFA date because the FDA's decision-making process can vary based on numerous factors. However, the FDA aims to adhere to the PDUFA dates as closely as possible, and decisions are typically made within a reasonable timeframe around the scheduled date. In some cases, decisions may be made a few days before or after the PDUFA date due to various factors such as the complexity of the application, the need for additional review, or other regulatory considerations. Overall, while the FDA strives to meet PDUFA deadlines, exact adherence to the date may not always be possible.




Then, let's keep going:

When is the last time the FDA made their decision exactly on the PDUFA date?

ChatGPT
As of my last update in January 2022, I don't have access to real-time or future data, so I can't provide the latest example of the FDA making a decision exactly on the PDUFA date. However, it's worth noting that while the FDA aims to adhere to PDUFA dates, decisions may be made slightly before or after the scheduled date due to various factors, including the complexity of the application and the need for additional review. For the most up-to-date information on FDA decisions and PDUFA dates, you would need to consult recent sources or the FDA's official announcements.

You
Can you provide an example when the FDA made their decision exactly on the PDUFA date?

ChatGPT
One example of the FDA making a decision exactly on the PDUFA date is the approval of Trulicity (dulaglutide) for the treatment of type 2 diabetes. The FDA's decision to approve Trulicity occurred on September 18, 2014, which was the exact PDUFA date set for the drug's application. Trulicity is a once-weekly injectable medication used to improve blood sugar control in adults with type 2 diabetes. This decision demonstrated the FDA's commitment to meeting regulatory deadlines and ensuring timely evaluations of drug applications.

[huntingonthebluffs]

biopearl123 to your point regarding how big the accomplishment for Geron / Imetelstat, it is truly off the scale.

If there was a single disappointment for me in all of this it was failure to go after frontline treatments but again I believe J&J was in control of the CTs and they for whatever reasons went after 2nd/3rd lines. Would be something I would like to know why vs just our suppositions. It has and always appeared to be the longest path which prevented patients from access for so many years as many of us watched family members and friends die from MPNs. Hopefully the trajectories going forward after approval changes the rate of Imetelstat related approvals.

And to Ryan thanks for your creative AI research on approvals around PDUFA dates. It would also be interesting to plug in for IND related applications as it seems the resistance by the FDA has been excessive. Secondly, I suspect you also did a similar analysis around CRLs, if so can you share? TIA

[cheng_ho]

The most important part of perspective is watching the other companies in the same space. Read the data that MAIA presented at ASCO:
https://d1io3yog0oux5.cloudfront.net/_6 ... g_Deck.pdf