Oncolytics Biotech Inc T.ONC

Accelerated Approval, surrogate endpoints, registration

[Noteable]

When studying a new drug, it can sometimes take many years to learn whether a drug actually provides a real effect on how a patient survives, feels, or functions. A positive therapeutic effect that is clinically meaningful in the context of a given disease is known as “clinical benefit”. Mindful of the fact that it may take an extended period of time to measure a drug’s intended clinical benefit, in 1992 FDA instituted the Accelerated Approval regulations. These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint. Using a surrogate endpoint enabled the FDA to approve these drugs faster.

A surrogate endpoint used for accelerated approval is a marker - a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Likewise, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality (IMM). 

Using surrogate or intermediate clinical endpoints can save valuable time in the drug approval process. For example, instead of having to wait to learn if a drug actually extends survival for cancer patients, the FDA may approve a drug based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit. In this example, an approval based upon tumor shrinkage can occur far sooner than waiting to learn whether patients actually lived longer. The drug company will still need to conduct studies to confirm that tumor shrinkage actually predicts that patients will live longer.

Where confirmatory trials verify clinical benefit, FDA will generally terminate the requirement. Approval of a drug may be withdrawn or the labeled indication of the drug changed if trials fail to verify clinical benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with the drug (e.g., show a significantly smaller magnitude or duration of benefit than was anticipated based on the observed effect on the surrogate).

 

https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/accelerated-approval

 

 

[Noteable]

On Dec 29, 2022, US President Joe Biden signed The Consolidated Appropriations Act into law. This wide-reaching Act contains notable reforms to the US Food and Drug Administration (FDA) statutory and regulatory frameworks. The legislation amends key regulatory frameworks, including changes to the FDA-expedited approval programme, Accelerated Approval. This pathway has been substantial for drug

[Noteable]

"Registration enabling campaign for accelerated development" is a program that Roche / Genentech employs https://dc.engconfintl.org/ccexvi/241/

[Noteable]

An example of the use of Registered Enabling Trial as defined in the Licensing Agreement between “AstraZeneca” and Sierra Oncology, Inc Page 10. 1.96. “Registration Enabling Trial”,  means, with respect to a Licensed Product, a human clinical study (whetheror not designated a  Phase 3 

[Noteable]

Sierra Oncology was subsequently acquired by GSK in 2022. 

[Noteable]

Sierra Oncology's acquisition gave GSK an experimental myelofibrosis treatment known as momelotinib, which previously passed through the hands of three other drugmakers. The drug was initially developed by Cytopia and then YM Biosciences before Gilead acquired YM and momelotinib. But mixed results in one trial and negative data in another led Gilead to give up on momelotinib, sending its

[Noteable]

A Registration Enabling Study is a continuation of a formally registered Phase 2 study, as outlined in the below referenced AstraZeneca and Sierra Oncology licensing agreement, which means that the protocol is the same as the Phase 2 study, thus accelerating the product approval process, and putatively moving pelareorep towards an Accelerated Approval and ultimately a full product marketing

[Noteable]

Quote: " If a human clinical study is denominated not a Phase 3 Clinical Study (for example, human clinical studies formally registered as Phase 2 clinical studies) then it shall only be treated as a Registration Enabling Trial ."

[Noteable]

" Registration-Enabling Phase II Trial means a Phase II Trial of the Licensed Product that (a) would, based on interactions with a Regulatory Authority or otherwise, (1) satisfy the requirements of 21 CFR 312.21(c) or corresponding foreign regulations or (2) is designed in a manner to allow for the addition of additional

[inthno]

For those that are suggesting that the company has removed all references to phase 3 it all depends upon the terminology being used. From the August 2023 investor presentation the graphs showing the trial phases and how far along they used to be always said phase 1 , phase2 and phase 3 and yes that has changed in the latest from phase 3 to license enabling study.....BUT also in the same

[Azzak34]

It's simply to allow us to apply for approval mid trial or when the prerequisite primary endpoints have been met, or look like they're going to be met.  "Traditional" phase 3 could take 3-4 years, by which time our patent may be close to running out, giving us very little or no bargaining power regardless of results.  With the licensure enabling we have more leeway to

[Noteable]

Not quite. An Accelerated Approval can be requested as soon as the FDA sees the study protocol and patient enrollment has begun. The Registration Enabling Phase 2 Study satisfies the FDA's protocol requirements and patient enrollment will be a continuation to ONCY's Goblet-1 Phase 2 pancreatic cancer cohort study. thus meeting FDA's requirements for registration and their Accelerated

[Azzak34]

Understood but the point I'm making/ reiterating is that we're not running a phase 3 to sit and wait until the end of it to submit for approval or decide next steps. The name of the next step, phase 3/ licensure enabling etc is irrelevant. We're full steam ahead to get this to market.  As dude has said institutions are starting to increase their stake which means they agree with

[Noteable]

Yes I totally agree with you Azzak34 ... "we're not running a phase 3 to sit and wait until the end of it to submit for approval or decide next steps ... We're full steam ahead to get this to market. "

[lonc17]

The concern I have is that while all Phase 3 trials are inherently 'registration enabling,' not all 'registration enabling' trials are Phase 3. The alteration made to ONC's investor presentation, where all references to Phase 3 were replaced with 'registration enabling' or similar phrases, seems like a preemptive measure by ONC to address the disappointment arising

[Azzak34]

Is that you dont think it'll happen or you don't want it to happen?  Matt has been talking about a Licensure enabling study as the next step for at least 7 months. Even when we had Pancan on board this was the wording. Go back and listen to the calls, firesides, interviews etc.... he's always said Licensure enabling study. The Phrase phase 3 has never been mentioned.  You

[Noteable]

" The path we're on makes everyone, who actually has shares, a lot of money in the near to mid term." Agreed Azzak34

[Noteable]

And just as a reminder .." The path we're on makes everyone, who actually has shares, a lot of money in the near to mid term."

[Buckhenry]

Something will have to happen one way or another in the near term... they are running out of money. Clocks ticking dude. 

[Peladawn]

Wow!   You figured that out all by yourself, Bucky?!

[Lesalpes29]

Reading in it a very good development. Maybe just maybe with ower future partner (BP like Roche!) to support us and to help us. Have a good sunday,

[Buckhenry]

This post has been removed in accordance with Community Policy

[Peladawn]

Yes, and apparently you didn't even have to finish sixth grade, either.

[Buckhenry]

How did you know that peladuffus?  MIT recruited me into their engineering program  before I finished the 6th grade. 

[Azzak34]

Bucky does the I stand for illiterate? 

[Peladawn]

Although that is incredibly hard to believe, it could certainly be possible, concidering MIT's use of their woke DEI Program that provides scholarships for the intellectually challenged. 

[Peladawn]

Especially since you were the only 21 year old in your sixth grade class.

[Buckhenry]

This post has been removed in accordance with Community Policy

[Azzak34]

It's weird you know the process for that! 

[Buckhenry]

The reason I know is I give back to my community to help those less fortunate to try and become better people and an asset to their community. Maybe you get your GED you could one day become an asset  instead of a liability in your community assak. 

[Azzak34]

So someone who helps their community become better people is using the mechanism of his kindness as a slight to someone on a message board?  So what your saying it if Pelaboost did go back for a GED he'd be some kind of loser? Doesn't that go against the very ethos of the good you're trying to do?  I've worked with a down syndrome kid before, should I use his condition

[Buckhenry]

One would think after all the endless pumping by pumpers anonymous on here in the last several years this stock would be bought out or at least $20 a share. Guess the market is not paying much attention here. Maybe if the pumpers could put in a little more zeal in their post we can get there. But I'm sure prosperity is just around the corner..... 

[Noteable]

It will soon enough.

[Noteable]

Meanwhile ... a " Registration-Enabling Phase II Trial means a Phase II Trial of the Licensed Product that (a) would, based on interactions with a Regulatory Authority or otherwise, (1) satisfy the requirements of 21 CFR 312.21(c) or corresponding foreign regulations or (2) is designed in a manner to allow for the addition

[Quentin30]

Perhaps to dispell ANY doubt, ONCY could have phrased registration enabling study with "Registration Enabling Phase II". It's either always deliberately vague to draw new money in, whilst weariong rose-tinted specs... or its an oversight. I would hope they clarify potential pathways at the forcoming panel meeting. Enough of the smoke screen Matt... Either you have data to support

[Azzak34]

Yessss the oracle has returned!!! Rough week babe? You're the new Jim Cramer round here with your big stock picks.  Are you day drinking? Who is ONVY?  What a pile of garbage. The trial has to be run whether we get AA or not! The approval could be pending no? Why, as a dedicated shareholder of "ONVY", would you paint it negatively when the alternative is just as likely

[inthno]

Hey Azzak, so why did you have to draw me into your post....mine was an opinion as is everyone else on this board and no one knows better than anyone else.... As for AA, yes I do not think it is possible at this point in time or it would have happened by now but that is not to say that it will not happen after they get the phase 3 trial started and then have their first set of result.... As for

[Azzak34]

Yeah and your pal Quentin just made the same point. Therefore I lumped the 2 people who said the same thing in together, that's unreasonable to you?  I have the same insight you do but I have the good grace to not whinge every day things don't go my way and drag everyone else in to it.  Talk us through the "if it hasn't happened by this point it isn't on the cards

[inthno]

I did not say I know what the status of AA is right now, I said I do not think it is in the cards at this time and IMO, for some reason you seem to think otherwise. So I guess we will see what comes first, the hopeful phase 3 or AA, what do you really think? Either way the company needs to get something going of substance and sooner than later rather than constantly talking about it and the purple

[Azzak34]

I'm happy to say I don't know. However, the path is fairly straightforward with a licensure enabling study. As your pal Quentin says we are on the clock for our patent as it expires in 2028. We can't allow ourselves to get near that as the closer we get to that expiration the less negotiating power we have. If you think the Board/Advisors don't know that then you're less smart

[Noteable]

That's exactly right Azzak34. The path is straighforward and is ultimately governed by the FDA. ONCY is now moving into a registration study with the FDA's guidance. And Matt Coffey had already stated that registration would be on Goblet-1 Phase 2 study - which clearly emphasizes the same study protocol, and an expansion of patient numbers to facilitate an Accelerated Approval application.

[inthno]

MIne was just an opinion as is everyone else on this board. But good thing that Note's and Azzaks are the only ones that count and make sense.... Oh yeah I almost forgot, we were approved 7 years ago for an mbc phase 3 trial with a spa and even though we have the biomarker we are now still 7 years later looking for guidance.... Tell me , all knowing, just how much shareholder value has this

[Noteable]

And your "trigger-happy" opinion inthno, is as bad as this last post of yours, since very little of what you say "holds water", and you have never provided any proof to what you say, when asked. So inthno, you are as phoney as a $3 bill. 

[inthno]

at least a 3 dollar phoney bill is worth more than a share of onc right now.

[Azzak34]

See, it wouldn't be because it's a phony $3 bill. You can sell right now and gosh darn it I wish you would. I hear Crispr is doing great, try that. 

[Quentin30]

Thanks Azzak, Yes CRISPR is doing great...  it's dropped from the recent high of 90 dollars per share, but that's given would be investors a chance to get on board for a lower cost basis...  excellent news I'd say... If you compare CRISPR performance to that of ONCY since I recommended you buy it at the end of October...shucks, it's only UP 75%. ONCY... ? well, it's

[Noteable]

Quentin30 it's surprising how out of date you are concerning ONCY, especially now that Big Pharma is beginning to successfully  report on their research with mRNA vaccines in pancreatic cancer, thus opening the vaccine/OV space for further investment dollars and acquisitions of companies currently opening up this novel 4th pillar of cancer treatment area of cancer immunotherapeutics.

[Noteable]

BTW crispr stick is down to $64 from its high of $200 in Jan 2021. Just sayin' that health technology often takes time to prove itself, particularly if it is innovative and novel. And cell and gene therapy hasn't proved itself because of the complexity of the human immune system, where if one tries to change one thing another unexpected thing happens due to homeostasis. That is why a

[Noteable]

Should read: crispr stock is down to $64 from a high of $200.

[Noteable]

Additionally, and as importantly, ONCY's oncolytic virus pelareorep is administered through intravenous (IV) injection rather than intratumoral (IT) injection, which is the route most other oncolytic viruses are administered. Consequently ONCY's pelareorep has few OV competitors since IV administration is the route that Big Pharma wants. And not IT.

[Noteable]

So .... among other things, intratumoral (IT) injection has not been used in routine clinical practice. Firstly, the safety of an intratumoral procedure is a prime concern in identifying lesions that are safely accessible and injected without causing tumor spread and hemorrhage. Secondly, specialized handling and patient immobilization is required to utilize a delivery device for the

[Azzak34]

Haha some one got a lil defensive. How many days you pore over this diatribe? I love that you're having to use the ole "buy the dip" defense for Crispy. So your trading it or are you holding? And are you going to apologize for pushing a stock on a different board then losing money for anyone who was dumb enough to listen?  Again, here's the difference between us. I have

[Noteable]

'Trigger Happy" and Phoney inthno would have you buying a phoney $3 bill than one share of ONCY. So he has unwittingly revealed his purpose for being here.

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inthno wrote ... "As for AA, yes I do not think it is possible at this point in time or it would have happened by now..."     REALLY? Tell us why. You obviously didn't or couldn't understand the reasoning so far.

[Noteable]

Specialty drugs, which are typically composed of large molecules that need to be injected or infused, as a category, represent roughly 50% of pharma spending today and continues to increase. Apr 16, 2024 The global oncology market size was valued at USD 222.36 billion in 2023 and is poised to grow from USD 242.15 billion in 2024 to USD 521.60 billion by 2033, growing at a