FDA Thoughts on Accelerated Approval

Forum rules
- Comments must be civil and on topic
- Back up claims with evidence/reasoning/sources (posting links is allowed)
- No commercials/harassment/spam
Post Reply
j6proulx
Posts: 23
Joined: Mon Jun 25, 2018 10:20 pm

FDA Thoughts on Accelerated Approval

Post by j6proulx » Wed Jul 18, 2018 7:34 pm

I found these articles to be of interest with respect to the FDA's approach to supporting accelerated approvals of single-arm studies that do not include a placebo/control arm. The articles are authored/co-authored by Gideon Blumenthan, MD, who is the Deputy Director (acting) of the Office of Hematology Oncology Products, Office of New Drugs, for the FDA's Center for Drug Evaluation and Research:

Top 10 Myths About FDA’s Office of Hematology and Oncology Products
http://www.ascopost.com/issues/november ... -products/
Myth #3: FDA’s OHOP requires randomized trials with overall survival as the endpoint, requires enrollment of U.S. patients, and does not permit crossover.

Fact: Actually, there are at least three myths embedded in this one statement. In oncology, as opposed to other therapeutic areas, FDA approves most drugs based on a single trial due to the challenges involved in repeating a positive trial given the high unmet medical need in oncology. Although randomized controlled trials are the gold standard design, and overall survival is considered the ultimate clinical benefit endpoint because it captures critical efficacy and safety data, OHOP has repeatedly approved drugs on the basis of single-arm trials with high objective response rates and long durations of response.

and

Oncology Drug Approvals: Evaluating Endpoints and Evidence in an Era of Breakthrough Therapies
http://theoncologist.alphamedpress.org/content/22/7/762
Overall Survival Endpoint: Limitations

An improvement in overall survival may be impractical or unreasonable to demonstrate in randomized controlled trials in selected disease areas. Unlike other therapeutic areas where placebo‐controlled trials can provide a comparator for the demonstration of overall survival, the use of placebo‐controlled trials is limited in life‐threatening diseases, especially for novel drugs demonstrating improved biologic activity in early drug development. For drugs demonstrating unprecedented activity in early clinical development in cancers with few effective options, the ability to randomly allocate patients to either an agent with markedly improved durable response rates or to a toxic and marginally effective comparator may not be feasible because equipoise may not exist [27], [28]. If a randomized trial is conducted, many investigators and patients request a cross‐over to the investigational arm. Cross‐over may confound the demonstration of improvement in overall survival and require that the trial have an alternate endpoint. As was observed in trials randomizing patients with EGFR‐mutant or ALK rearranged advanced NSCLC to either targeted therapy or chemotherapy, high cross‐over to the experimental arm confounded the interpretation of overall survival [29], [30], [31], [32]. The use of alternative endpoints, such as progression‐free survival, provides a clinically relevant endpoint and allows expeditious access of important drugs to patients.

A demonstration of improvement in overall survival may not be practical in cancers with long natural histories. In part due to improved systemic treatments, patients with advanced cancers such as CLL, MTC, multiple myeloma, and CML now have 5‐year survivals upwards of 50% [33]. In these diseases, the time required and large patient numbers needed to power a trial to detect a survival improvement would not be practical and could deny effective treatment to patients, which would also negatively impact innovation.

It's hard to read those passages and not think of imetelstat and IMbark as a prime candidate for accelerated approval.

Dogonenuts
Posts: 40
Joined: Tue May 10, 2016 6:13 pm

Re: FDA Thoughts on Accelerated Approval

Post by Dogonenuts » Fri Jul 20, 2018 1:25 am

I would agree, both of these are screeming both Imbark and Imerge! Just a matter of time.

Thanks for posting.

biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Re: FDA Thoughts on Accelerated Approval

Post by biopearl123 » Tue Oct 16, 2018 2:57 am

J6, I moved your post to the top of the list since it provides a lens through which we might interpret the up coming ASH presentations. I found these articles particularly reassuring and if we see good data, they may prove relevant. Janssen made a big deal about billion dollar pipelines. So what if Imetelstat is not a billion dollar drug if it works and enhances available treatment options. Regard, bp

Zhears
Posts: 74
Joined: Mon Oct 08, 2018 12:19 pm

Re: FDA Thoughts on Accelerated Approval

Post by Zhears » Tue Oct 16, 2018 10:39 am

For accelerated approval I thought part of the process was to inspect the manufacturing facilities of the company.

Geron still needs to resolve that question. Out sourcing it to already existing facilities or building there own.
Either means that the approval isn't just around the corner.

Secret Third Arm
Posts: 31
Joined: Tue Aug 28, 2018 3:26 pm

Re: FDA Thoughts on Accelerated Approval

Post by Secret Third Arm » Wed Oct 17, 2018 12:46 pm

Not entirely true. JNJ is contractually obligated to continue to manufacture Imetelstat for Geron for 2 years. I'm fairly certain whatever facility they are doing that in is more than adequate to meet FDA regulations.

biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Re: FDA Thoughts on Accelerated Approval

Post by biopearl123 » Fri Oct 26, 2018 2:33 pm

Agree that for ongoing studies Janssen has to provide drug but not for new studies or if drug approved. I hope Geron has contracted with the existing producer of Imetelstat otherwise the FDA hurdles re a new facility will be huge. bp

biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Re: FDA Thoughts on Accelerated Approval

Post by biopearl123 » Sat Oct 27, 2018 12:02 am

I may be wrong about that. Janssen provides for two years. bp

Post Reply