Strategies for Biotechs Planning FDA Approval Pathways in Current Financial Market
As the biotech financial markets shift from a peak 12 months ago, even well-funded biotechs are watching pipeline burn rates as uncertainty surrounds the next investment rounds.
There is however positive news from the investment sector on future demand. According to Fred Cohen, co-founder, and chairman of Monograph Capital Partners in San Francisco “pharma has a tremendous need for new products and it will only accelerate over the next eight years”. But he said what investors want is real innovation, “not slightly better because the payers are not going to pay you for just slightly better.”
Meanwhile, industry experts tapped by Novotech are pointing to the Asia Pacific for biotechs wanting to conserve funds while rapidly progressing their clinical programs, which also supports investment attraction for later phase research.
THE ASIA PACIFIC BENEFITS
Fred Cohen points to the benefits of having Asia Pacific sites that offer vast patient populations.
“Frankly, there are diseases where it’s easier to recruit in Asia where those diseases are more prevalent,” he said.
He said there are a number of places where it makes sense to extend your reach to recruit faster while you’re thinking about optimizing spend. “What you are pushing hardest for is time to last patient in.”
“The more you can shorten that, the more you can shorten the readout on your trial, which is ultimately what will be the fuel that will drive the subsequent growth of your company.”
“Everybody tells you you had better cut your spend probably by 10% or 15% and you had better focus that spend
on your asset that is farthest along.”
“That is, you will focus on your Phase II or your Phase Ib asset and reprioritize preclinical work which is a polite way of saying, You’ll put it on the shelf until you can afford to do it.”
That discussion is being reiterated in boardroom after boardroom after boardroom because ultimately what will make a biotech company successful is clinical data in its lead asset.
That’s where the value gets created and everyone knows it.
Discussing the advantages of a China presence Yi Larson, the chief financial officer of LianBio based in Shanghai, said that the founders Perceptive Advisors “saw a real need to build a new kind of company with the ability to accelerate Chinese patient access to innovative new medicines”.
LianBio is a cross-border biotech company with offices in China and the US focussed on bringing innovative drugs to China.
“What we’ve seen in recent years is new government policies that have been enacted to improve health outcomes. Many of these policies have really helped the biotech ecosystem in China to flourish.”
“At LianBio we in-license medicines uniquely suited to the Chinese market and have established a robust clinical development, regulatory, and medical affairs infrastructure operating on the ground in China.”
Addressing the current investment market, she said “We’ve certainly been very mindful of the current market conditions and have been disciplined about our cash management.”
“At the same time, we are fortunate to be well-capitalized and in a position to continue to invest in our
priority near-term commercial stage programs and launch readiness activities for these programs.”
“I’ll say also that in this current environment, what we have seen is an uptick in interest from potential western biotech partners in pursuing these regional deals.”
Commenting on potential locations for global trials Jeanne Novak, CEO, and president of CBR International in Boulder, Colorado said places like Australia offered significant opportunities, especially for early phase clinical studies. The region offers “incentives and the opportunity to get into really high integrity, very high-quality Phase I opportunities”.
CBR International develops global clinical development plans for its US and European biotech client base.
“There is absolutely a shift in the development patterns that we’re seeing in early clinical trials, and it is primarily based on the availability and speed of obtaining opportunities to get into Phase I trials,” said Jeanne Novak.
The shift that we’re seeing is because of many delays and some delays in trial start-up due to limited capacity and increased demand for CRO services. This is also true for getting into CRO’s Phase 1 units, et cetera here in the States; and even to some degree, in Europe.
Australia, for example, has become much more of a target for a lot of our early startup companies as well as young companies that might be into their second or third product in their pipeline wanting to get clinical data early.
These clients are shifting their strategies for early development to places like Australia where the incentives and the opportunity to get into really high integrity, very high-quality Phase I opportunities exist. We are seeing that shift.
Yi Larson said expanding clinical trials to China is a real option for biotechs wanting to quickly recruit patients.
She said while we’re not developing for the US market, when working with partners “we typically contribute anywhere from 15% to 20% of the global trial enrolment from China as part of that global trial, and we’ll leverage that global trial for approval both in the US as well as in China”.
“Our core model is to in-license programs for development in China and other APAC regions.”
We like to bring in programs that are at a stage where we can add value to the global program.
For example, by contributing to Phase III trial enrollment.
I can tell you that the ability to contribute patients to a global program can be very meaningful to US-European-based partners.
Before I was at Lian, I was the CFO of Turning Point Therapeutics where I led the out-licensing of China rights to our lead programs.
The reason that we were interested in a regional deal was because of the clinical development resources, the partner was able to bring to the table and the ability to quickly recruit patients, particularly in trials of precision medicine can be very attractive.
Another way that we are maximizing value for clinical programs is by pursuing region-specific indication strategies.
For example, we’re studying our FGFR inhibitor Infigratinib, in gastric cancer, which has a higher prevalence in China than in any other geography.
Indication expansion can generate value on a global scale while also allowing our partners conserve their resources.
CHINA AS A DESTINATION FOR CLINICAL TRIALS
In terms of accelerated development pathways in China there has been a lot of change according to Yi. “Particularly over the last few years that I think makes it such an exciting place to be operating in biotech right now.”
“That comes in many forms. Regulatory reforms, we’ve seen China joining the ICH which has enabled that ability to join the global clinical trials, also accelerated regulatory pathways, which include priority review, breakthrough therapy designation, and clinical trial waiver programs, so mirroring a lot of the programs that we already have in the US as well as significant government support to really foster innovation.”
That’s through their policies, strategic investments in the sector, and supporting growth in the infrastructure in China.
We’re also seeing an improved reimbursement system through the national reimbursement drug list, which now sees annual listing updates.
“It used to be much less frequent which are driving more rapid and greater access throughout China as well as stronger IP protection. All of those things, I think, are making it a much more favorable environment to be operating in and also much more aligned with the global development.”
THE FDA APPROVAL PROCESS
Yi also commented on the FDA approval process around multi-center trials.
“The FDA has actually been very clear about their requirements to get FDA approvals.”
“They’re looking for multi-center randomized control clinical trials which demonstrate applicability to the patient population in the US.”
“They also want to make sure that primary endpoints are applicable to the standard of care in the US and that the control arm is also applicable to standard of care in the US. These are all incredibly important.”
Jeanne Novak agreed saying “The FDA is actually very open to clinical data coming from outside of the US”.
“With regards to, again, Phase I studies that are designed and conducted in Australia, for example, it’s known that oftentimes the data and the safety data collection and monitoring is, again, of such a high quality that these data are readily accepted by the FDA.”
“Certainly, if the study is designed appropriately, these results can absolutely springboard a program directly into a Phase II or maybe a Phase Ib with an expanded opportunity to continue evaluating dosing and schedule.”
“Oftentimes, we advise that if it’s possible to get early clinical data in a Phase I, normal healthy volunteers again, in Australia, that oftentimes it can be very important information for filing even an early application with the FDA; or can serve to support a request for a meeting to actually discuss the data and not just bring it in to support the Phase II. These data can actually serve as a basis for discussions with FDA to help build a clinical development program with the FDA.”
I think a bigger part of the approvability piece starts early in development. It is important to begin early thinking about how to try to establish what are the benchmarks of safety and the efficacy endpoints for a particular product and clinical indication. This is important when designing and initiating early clinical studies that can be designed to provide meaningful early clinical signals.
Also, early trials conducted outside of the US can address some of the some of the key elements of pharmacokinetics early before we begin thinking about Phase ll, lll and global trials.
Endpoints that are in fact clinically meaningful, which is a big topic with the FDA right now, not only need to be statistically significant but clinically meaningful for the population that you intend to treat. These considerations can be piloted in early studies.
She said “building those attributes and those considerations early in your trials and looking for those types of benchmarks and paying attention to not only the design and adding value to the trial, but also the outcomes you’re looking for can actually guide that development program towards those pivotal efficacy studies that can in fact result in approval in the US.
PRECLINICAL PROGRAM GUIDE
The need for early planning and defining a robust preclinical program was also addressed by Kasey Kime, the Director of Regulatory Affairs at Novotech. She said there are 3 main points for biotechs to consider:
- The first is to know your product. Begin your product characterization early, develop your target product profile, and your associated quality target product profile. This will help you uncover challenges to your development program.
- The next tip is to take advantage of all available health authority meetings.
Educate yourself on which meetings you are eligible for and use this as an opportunity to discuss those developmental challenges.
This is going to help you focus your development and help save time and money and improve your overall chances of filing success.
- My third tip would be to think beyond Phase I.
For example, if you are considering applying for accelerated approval, you need to consider the impact of that on your overall development timeline because often the clinical development can move faster than the traditional CMC.
You need to give early consideration to expediting your CMC development if accelerated pathways are part of your strategy.
In addition, she said, Australia is an attractive early-phase destination.
“Some of the well-known reasons for this are the rapid start-up timelines,the overall lower cost of the trials due to the tax rebate program, and the efficiency of the regulatory pathway.”
It’s quite a streamlined regulatory pathway under the CTN pathway and of course, the quality of the clinical trial data coming out of Australia.
“For those reasons, it is a very attractive place for early phase trials.”
She said in addition, if a biotech has an open US IND, they are eligible for the CTN pathway in Australia.
She said that means some of the “biologicals like the CART T therapies, if you have an open IND, you can discuss with the TGA, and there is the ability to streamline that clinical trial under the CTN pathway.”
“Australia has a world-class health system and data is accepted by major regulators like the FDA and the EMA for future clinical trials.”
TOP TIPS FOR BIOTECHS ENTERING CLINIC
1. Fred Cohen, co-founder and chairman of Monograph Capital Partners in San Francisco
“Think hard about your target product profile and make sure that it will matter.”
“Having thought about that, make sure that the clinical trial that you’re working on ends up being supportive of the direction you’re headed in.”
2. Jeanne Novak, the CEO and president of CBR International Corp in Boulder, Colorado
“Absolutely think about the long-term goals and be flexible as you are willing and able to collect clinical data.”
“Assess those data appropriately and see if you’re still on target for what your original plan might have been and make the adjustments early so that you’re not falling so much in love with what your original theory might have been, but rather what the data are telling you.”
“Quickly pivot if needed and continue on a path to, again, developing excellent and high-integrity clinical data.”
3. Yi Larson, the chief financial officer of LianBio in Shanghai
“I think as it relates to a global development program, if you are thinking about doing a regional or global deal, the choice of partner really matters.”
“The deal itself is just the beginning of a long-term relationship that requires very close collaboration in order
to realize the full value of the deal which often entails a great deal more work than most people expect, so plan ahead, think about the timing, and the choice of that partner. That really matters.”
4. Kasey Kime, the director of Regulatory Affairs of Novotech
“I would say think carefully about your choice of CRO partner.”
“You want to pick a CRO with a proven track record and experienced staff in your therapeutic area.”
BioDesk is Novotech’s in-house regulatory consultancy group.
“We’re a little different to other regulatory consultancy groups by the fact that we’re actually part of global CRO Novotech that specializes in biotech.”
Because of that, we get to see a lot of innovative products and we get to work with a lot of different global health authorities, and we get to see how they treat these innovative products.
This kind of experience is highly valuable to our biotech clients, many of which are working right at the cutting edge of science in areas where the regulatory guidance is limited or not yet developed.
“I would say our major strength at BioDesk is being part of a global CRO that specializes in biotech.”
The China Biotech Landscape – Opportunities in China and the Path to USFDA Approval” is available to download here: https://novotech-cro.com/whitepapers/china-biotech-landscape-opportunities-china-and-path-usfda-approval