Along with the acquisition of Immunex in 2001 - mostly to gain rights to Enbrel, which DID turn into a ginormous blockbuster - Amgen acquired a hodgepodge of early and mid-stage leads in the Immunex pipeline.
In most acquisitions like this, it seems like there is little value placed on the early leads of the target company - most of the attention is on the flagship, late stage product (Enbrel, in this case), and even then, the incoming programs & leads have to compete for resources with the incumbent R&D programs. Since these early stage leads have little data accumulated, and may involve new biology, little ever becomes of the "bonus" leads. (Also, after a merger, the acquiring company becomes even more of a "product" company, and also needs to cut cash costs post-merger to meet the financial expectations justifying the merger.)
Hats off to Amgen, though, for sticking with a lead sourced from Immunex, as today it was disclosed that an antibody targeting HGF (for cancer) has enough anti-MET activity that it generated strong response in certain gastric cancers.
(The Amgen antibody is referred to as either AMG 102 or rilotumumab. An excellent press release with lots of technical details is here, including the survival data. (11.1 months overall survival WITH AMG 102 versus 5.7 months without for patients with high MET expression.)
This story is really exciting for a reason beyond the notion that we might have another weapon in the war on cancer, and the notion that Amgen is a great research organization.
Searching Clinicaltrials.gov leads me to believe that this trial is the one that generated today's good news. If so, note that the trial was launched nearly four years ago, and there is NO mention of MET protein or biomarkers in the trial design.
It seems to me, then, that some astute Amgen researchers - after the trial started and likely after Amgen had already concluded that AMG 102 wasn't effective enough to continue development - decided to sift through the results on a patient by patient basis to see if there was a genomic commonality with the responders. The researcher (or team) then used either a shotgun profiling approach to identify a biomarker to stratify the patients or decided to specifically assay for MET expression. I'd guess that the first approach was used, but either way, Amgen boldly applied genomic technology to do something oft-rumored but seldom seen - a biomarker-driven compound rescue.
(And even if I'm wrong, and Amgen was onto MET stratification all along, it is still an impressive finding.)
To temper the excitement somewhat, the clinical trial found only 27 of 82 (32%) gastric cancer patients in the trial had over-expressed MET protein, so it is likely then that the FDA label for AMG 102 - like Xalkori - will be very targeted and linked to a companion diagnostic. However, as discussed here before, MET is a hot target with likely broad applicability, so AMG 102 might someday reach blockbuster status.
Also, due to its' origins back in Immunex's labs, 11 or more years of the patent life of AMG102 may have already lapsed. I would guess that someone within Amgen has just been tasked with conjugating AMG 102 with something interesting in order to boost efficacy and reset the patent clock. (Immunomedics: make sure someone is manning your phones!)
The other possible winner here: Francis Collins & his NCATS initiative. Amgen's work on '102 reinforces that there is value in rummaging through pharma programs to find new applications.
AMG 102 is another manifestation of the Molecular Future hypothesis, and more proof that targeted therapy is effective. It sure seems like targeted therapies have a higher-than-average clinical success rate once safety has been demonstrated in a Phase I trial. (And maybe those targeted therapies that haven't succeeded just need the right biomarker.)
ADDENDUM: on reflection, I do not believe that Amgen's results are predictive of success for NCATS. My understanding now is that NCATS is less about further qualifying a lead through advanced technology (genomics, etc.) than about starting de novo development in new applications for drugs that have previously made it into clinical trials. Other than the fact that the compounds under consideration are likely safe for humans (i.e. the leads had successful Phase I trials), the NCATS approach provides no running start or any reason to anticipate better than average discovery success. (In fact, I'd argue that a bureaucratic organization like the NIH is LESS likely to have discovery success.)
On a positive note, let's hope that Amgen's success can be similarly applied to the rest of the bio-pharma industry.
Showing posts with label NCATS. Show all posts
Showing posts with label NCATS. Show all posts
Wednesday, May 23, 2012
Thursday, April 12, 2012
NIH to repurpose failed leads?
(Let's call them "shelved" leads instead of the pejorative "failed." Some of the leads just lacked the organization will, expertise, or budget necessary to justify the risk of further investment.)
I find Collins' idea VERY interesting for a few reasons:
- this seems like a good role for government DD investment - the NIH can provide some very worthwhile assets & expertise, especially as leads may be repurposed from one disease class to another. (say, cancer to allergy application.) No pharma company has the breadth of expertise that the NIH does across their Institutes.
- this looks like a high leverage role for the NIH - theoretically, a small incremental investment in a shelved lead that is already proven safe in humans could have a HUGE return. However, the nature of the quest says that there will be ALOT of failure along the way, so much failure that pursuit of this mission by the private sector isn't economical.
-Politics: Any clinical success can make the NIH's mission more tangible to those who fund the NIH. The NIH does some great research, but since it is heavily biased towards early, basic research, not a lot of it can be used as a 'trophy' to gain more funding. Also, from the NIH perspective, a "win" from repurposing can come a lot sooner than a "win" from de novo drug discovery by NCATS, and by the nature of the repurposing work, the NIH can't step on any toes. If a pharma has shelved a program, how can they object to the NIH building off their earlier work? (I think we all know how pharma execs run from failed programs like cockroaches when the lights are turned on.)
-Also, while I'm not in love with the idea of the NIH taking a formal role in translational research, this seems like a smart way to dip a toe into drug discovery. Perhaps the NIH's DD experience to come from repurposing will help improve the DD regulatory process.
The devil is in the details, and in this case, it's the IP. What happens if a chemical patented by Company A for Disease X is found to be effective in Disease Y? Who owns the resulting IPR? There's no shortage of failed/shelved leads for the NIH to consider, so might they only pursue leads off patent or nearly off-patent?
The only question that I'd ask the NIH is "why does the NIH believe they have a higher probability of success with the "shelved" leads than the originating pharma team?" I can think of a few reasons, but I'd like to hear their rationale from them.
Friday, March 16, 2012
NCATS' vs. Calibr (public vs. private translational medicine)
The NIH's National Center for Advancing Translational Sciences - has been controversial since first promoted a year ago by Francis Collins, head of the NIH. The controversy is due, in essence, because the NIH isn't the right vehicle for drug discovery. (See Derek Lowe @ In The Pipeline for a very sharp, accurate, extended opinion.)
As NCATS is still being formed, there hasn't been a lot of news or action taken on their stated strategy, but they announced their initial partnership this week: NCATS and Eli Lilly will work together to profile almost 4,000 compounds either FDA approved or under investigation. The main goal seems to be to establish other possible applications for these compounds (What does this compound for kidney cancer do in CV models?)
As a first deal, the NCATS-Lilly partnership is a solid one, as disseminating the resulting info in the public will add to the characterization of existing drugs, and hopefully the development of new therapeutic applications, very possibly at a high speed, as many of the drugs in the NIH database will have already received she level of clinical scrutiny.
As an indication of NCATS' direction, however, this deal is underwhelming. It's an easy extension of NIH assets and activities that doesn't justify the dedicated infrastructure of NCATS. The partnership could have been undertaken by the existing extensive NIH compound profiling efforts (the NCI-60, for example), or externally as grant funded research.
(Given that some partnerships take more than a year to negotiate, one could wonder if the idea for the NCATS-Lilly partnership actually pre-dates NCATS.)
With the announcement of NCATS last year, the NIH announced the termination of the NCRR (National Center for Research Resources - I'd never heard of it either), and in principle, I like the idea of taking a look at current NIH missions and assets and restructuring when ideal. (Science changes regularly - shouldn't the NIH change with it?) However, I still don't see what the NIH is bringing to drug discovery/translational medicine that doesn't already exist. I hope NCATS' next deal proves that they are not a solution looking for a problem to solve.
(btw: congrats and thanks to Janet Woodcock and others at the FDA who are similarly progressively looking for opportunities to restructure the drug approval process. The current FDA/NIH leadership is to be commended for their commitment to progress and regulatory process improvement.)
In marked contrast is the just-announced private, not-for-profit translational medicine institute sponsored by Merck, Calibr (short for California Biomedical Research). There is a huge need for somebody to shepherd along promising molecules between their discovery in a basic research environment (universities) and when they are "ripe" for commercial development by a pharma/biotech company, and while NCATS is a step by the government to address this need, I think it is much more the responsibility of for-profit life science stakeholders.
Merck is seeding Calibr with $90M (likely feeling to Merck like a ~$60M expense, after accounting for the tax deduction), and will receive a right-of-first refusal for resulting technologies. The investment by Merck will also be leveraged by government grant funding of Calibr R&D. I'm sure Merck could put more exact numbers to it, but they'll probably get the benefits of say $120M in R&D over the next few years, for a $60M investment. This makes TONS of sense, and to any economic development folks out there, this also results in lots of new US jobs.
In contrast, NCATS' budget in 2012 will be $722M, with $553M to come from retitling existing programs. (In effect, NCATS = ~ $169M in incremental translational programs, less start-up costs).
Anyone want to bet which is ultimately more productive, per dollar, NCATS or Calibr?
(BTW: to make my criticism more constructive, what I'd instead nudge the NIH more towards is post-approval research. I think there's a need for impartially-sponsored Phase IV testing, and also a need for simply more Phase IV testing. As an example, consider a new compound approved for a particular solid tumor cancer. Post-approval, the pharma concentrates on marketing the new cure, and clinicians begin experimenting on off-label uses on an ad hoc basis. The NIH could better organize this research, expand upon it by scaling, and mitigate the inherent conflict of pharma-run Phase IV trials.
Alternatively, I'd be in favor of taking the NCATS $$$$ and using it to re-restablish R&D at an abandoned Pharma site. (Such as the old Parke-Davis/Pfizer campus in Ann Arbor, MI.) There's plenty of R&D talent, experience, and assets already available, with a big bang-for-the-buck.)
As NCATS is still being formed, there hasn't been a lot of news or action taken on their stated strategy, but they announced their initial partnership this week: NCATS and Eli Lilly will work together to profile almost 4,000 compounds either FDA approved or under investigation. The main goal seems to be to establish other possible applications for these compounds (What does this compound for kidney cancer do in CV models?)
As a first deal, the NCATS-Lilly partnership is a solid one, as disseminating the resulting info in the public will add to the characterization of existing drugs, and hopefully the development of new therapeutic applications, very possibly at a high speed, as many of the drugs in the NIH database will have already received she level of clinical scrutiny.
As an indication of NCATS' direction, however, this deal is underwhelming. It's an easy extension of NIH assets and activities that doesn't justify the dedicated infrastructure of NCATS. The partnership could have been undertaken by the existing extensive NIH compound profiling efforts (the NCI-60, for example), or externally as grant funded research.
(Given that some partnerships take more than a year to negotiate, one could wonder if the idea for the NCATS-Lilly partnership actually pre-dates NCATS.)
With the announcement of NCATS last year, the NIH announced the termination of the NCRR (National Center for Research Resources - I'd never heard of it either), and in principle, I like the idea of taking a look at current NIH missions and assets and restructuring when ideal. (Science changes regularly - shouldn't the NIH change with it?) However, I still don't see what the NIH is bringing to drug discovery/translational medicine that doesn't already exist. I hope NCATS' next deal proves that they are not a solution looking for a problem to solve.
(btw: congrats and thanks to Janet Woodcock and others at the FDA who are similarly progressively looking for opportunities to restructure the drug approval process. The current FDA/NIH leadership is to be commended for their commitment to progress and regulatory process improvement.)
In marked contrast is the just-announced private, not-for-profit translational medicine institute sponsored by Merck, Calibr (short for California Biomedical Research). There is a huge need for somebody to shepherd along promising molecules between their discovery in a basic research environment (universities) and when they are "ripe" for commercial development by a pharma/biotech company, and while NCATS is a step by the government to address this need, I think it is much more the responsibility of for-profit life science stakeholders.
Merck is seeding Calibr with $90M (likely feeling to Merck like a ~$60M expense, after accounting for the tax deduction), and will receive a right-of-first refusal for resulting technologies. The investment by Merck will also be leveraged by government grant funding of Calibr R&D. I'm sure Merck could put more exact numbers to it, but they'll probably get the benefits of say $120M in R&D over the next few years, for a $60M investment. This makes TONS of sense, and to any economic development folks out there, this also results in lots of new US jobs.
In contrast, NCATS' budget in 2012 will be $722M, with $553M to come from retitling existing programs. (In effect, NCATS = ~ $169M in incremental translational programs, less start-up costs).
Anyone want to bet which is ultimately more productive, per dollar, NCATS or Calibr?
(BTW: to make my criticism more constructive, what I'd instead nudge the NIH more towards is post-approval research. I think there's a need for impartially-sponsored Phase IV testing, and also a need for simply more Phase IV testing. As an example, consider a new compound approved for a particular solid tumor cancer. Post-approval, the pharma concentrates on marketing the new cure, and clinicians begin experimenting on off-label uses on an ad hoc basis. The NIH could better organize this research, expand upon it by scaling, and mitigate the inherent conflict of pharma-run Phase IV trials.
Alternatively, I'd be in favor of taking the NCATS $$$$ and using it to re-restablish R&D at an abandoned Pharma site. (Such as the old Parke-Davis/Pfizer campus in Ann Arbor, MI.) There's plenty of R&D talent, experience, and assets already available, with a big bang-for-the-buck.)
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