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Volume 29, Issue 9
Stakes are high for emerging biopharmaceutical companies to get their relationships with CRO partners right from the outset.
Many emerging biopharmaceutical companies are highly dependent on the success of one product—usually their lead compound. Because of limited staffing and regulatory experience, many hire contract research organizations (CROs) to help them navigate the regulatory pathway, leaning on their expertise, foresight, and knowledge of the complex landscape.
Some emerging biopharma aren’t completely satisfied with their CRO relationships, and believe the CRO partners could be more responsive to their needs, particularly in light of the increasing role these smaller companies are playing in driving drug innovation—responsible for much of the life sciences industry’s R&D pipeline in recent years.
Emerging biopharma companies developed about 65% of the new drugs approved in 2018 in the U.S., according to IQVIA. In addition, of all companies sponsoring one or more clinical development program, 61% are not among the top 50 largest pharma. Moreover, 60% of FDA approvals in 2018 went to firms that had never before received an approval.
These small biotechs are under pressure to get CRO and vendor partnerships right from the start, much more so than for big pharma, because they cannot afford missteps that cost them time and money. The smaller operations simply don’t have the financial resources that larger pharmaceutical companies have, making the smaller biopharma more sensitive to such problems as clinical trial timeline delays, out-of-scope change orders, and cost overruns. For many, one poorly-designed clinical trial could end their existence.
The relationship between emerging biopharma and CROs continues to evolve, but are CROs, especially the larger ones, tailoring their service offerings enough for these fledgling, important players, given their unique operating constraints compared to big pharma?
It’s helpful to have all of the bells and whistles that new technologies can bring to a clinical trial, but small companies also need a high-touch relationship with CROs. Many are looking for close contact and good oversight on the part of the CRO. They want a service provider that’s mindful of their small-client needs. They don’t want to feel like they’re just a drop in the bucket of a large CRO’s business.
“With worries about cost overruns, financial issues, and paying enough attention to detail, I’m looking for a smaller CRO that I can connect with, who would be very responsive, and a contact there who takes on responsibility,” Audrey Rossow, senior director of clinical operations at Pulmatrix, Inc., a developer of pulmonary-delivered therapeutics, tells Applied Clinical Trials. While partnering with a CRO with pulmonary or rare disease expertise would be beneficial, Rossow adds, “We need, above all else, transparency, flexibility, and problem-solving skills from a CRO.”
As a small company running clinical trials, Rossow’s concerns include avoiding cost overruns and timeline delays, and executing properly designed trials with little deviation as possible from the trial protocol. Essentially, what’s important to her is a CRO partner that pays attention to detail and meets timelines, which in Rossow’s experience has not always been the case.
“For small biotechs, a week for us is like a month or two in terms of making decisions and getting things done. I don’t need the Titanic, I need a speedboat,” says Rossow, who has a deep background in clinical operations and project management; before joining Pulmatrix last fall, she was a consultant for 10years.
When interviewing CRO project manager candidates, Rossow notes that it’s the answers to the soft questions that are most telling. “What would a CRO’s tactical and financial plan be if they are 10 months behind in activating trial sites, or months behind their enrollment timelines?” she says. “I want a project manager at a CRO that I can completely connect with. In my career I’ve had to change projects managers at CROs, and it was the best decision I ever made because someone else came on board and got what I was talking about, and got things back on the rails.”
Mike McLaughlin, associate director of clinical operations at Dermavant Sciences, Inc., says the company is seeking a CRO partner with a mindset and culture similar to its own. “It’s important to find a CRO that’s a right fit from a culture standpoint, with a culture similar to ours, which is to be nimble, quick, and flexible, and offer a quick turnaround,” he says.
“We’re concerned that we’re just a drop in the bucket in a large CRO’s financial portfolio. So then how much attention are we going to get?” adds McLaughlin. “We need a CRO team that’s high quality, high performing, and offers overall support.”
Dermavant, a clinical-stage biopharma company focused on the development and commercialization of in immuno-dermatology treatments, has five candidates in various phases of clinical trials. McLaughlin says that for fairly small Phase I or II studies, he prefers to link up with a smaller CRO that’s more sensitive about costs and meeting deadlines. In addition, the contact person at the sponsor would likely be easier to reach to discuss any concerns, McLaughlin notes. In his experience, a smaller CRO can often provide an experienced, flexible, and responsive team with low staff turnover.
McLaughlin says it’s important for an emerging biopharma not to be “shoehorned” into a larger CRO’s system, where it’s more difficult to pick and choose the services and support the sponsor needs. The alternative can often be service offerings that are redundant to a biopharma’s internal capabilities.
When considering CRO partnerships, McLaughlin looks for quality and thoroughness in CRO proposals, which help quantify capabilities. He’ll also discuss the candidates with colleagues, but sometimes the decision ultimately comes down to gut instincts, he indicates.
“All sponsors are looking for quality, timeliness, and staying within budget from their CROs,” he says. “I want to keep changes and costs to a minimum.”
Among specific deliverables from CROs that emerging biopharma’s are looking for, according to McLaughlin, include:
“It’s important to calculate and track your interactions and activities along the established timeline,” he notes.
Possessing certain intangibles are key as well, says McLaughlin, such as trust, good communication, and being proactive. “A CRO team of high performers and experts will make it easier for us to develop a good relationship,” he explains. “It’s like dating. We’re trying to develop a good relationship. It’s an engagement that you’re about to go through, for better or worse, for the next six months, year, or longer. The clinical trial needs to have a good start for the relationship to work.”
Jim Barlow, CEO at ImmunoGenesis, Inc., which designs therapies targeting immune resistance in immunologically cold tumors, is planning for the company’s main trial to get underway in 2021. “As for a CRO partner, we’d be looking to link up with a company that has oncology experience, although it would not necessarily have to be exclusively oncology,” he says. “It’s important that they have some experience with oncology trials, and that they know the pitfalls and challenges in the area.”
Barlow notes that small biopharma companies have fewer resources, and thus are “laser-focused” on a single clinical trial most of the time. “The company team will know the ins and outs of that study, and will work on it every day. It will typically handle budget negotiations with the trial site partner, and most of the logistics around training and site initiation,” he says. “But if you’re running several trials, you’ll need a CRO that can take command and coordinate all of the trial work.”
Barlow would like to be able to pick from a menu of services and support offered by a CRO. For him, adverse event reporting, the statistical analysis plan, project management, and addressing regulatory issues would be very important.
“Being able to have a modular approach where you could pick only the services you need would help bring fixed costs down and would be a huge advantage,” Barlow tells Applied Clinical Trials. “We might have a trial operating at only two sites, so it’s not the same amount of legwork needed as if we had 50 sites. But we’re still going to need some of the key systems the CRO will offer, so I would like to negotiate on these.”
Another option for the smaller-sized sponsor, Barlow suggests, is considering hiring CROs on a consulting basis for specialty tasks, and still gain access, for example, to their statistical analysis group, adverse event reporting, or their knowledge of local markets and regulatory requirements.
Executives note that sponsors will sometimes encounter a serious design issue in the middle of their study that they didn’t plan for when initiating. “While a challenge for big pharmas, the impact can be significantly greater for smaller companies who already have much more limited budgets and resources to consider,” says Tanya du Plessis, vice president of data strategies and solutions at the Bioforum Group, which describes itself as a data-driven CRO, offering expertise in clinical data management and biostatistical analysis, among other services.
Essentially, big pharma organizations have large, cross-functional teams with an array of specialists in-house, unlike many smaller companies who do not have the budgets or scale to staff their teams as comprehensively—and with people who have deep experience addressing all the issues that can come up and disrupt a clinical trial.
“We try to understand how emerging biopharma companies operate,” du Plessis says. “We help them by offering smart solutions. We try to be nimble because we realize the limited options that small biopharma may have.”
CROs recognize the importance for sponsors in getting the right advice and guidance early on so that they can design the study properly and collect the appropriate data from the onset. “It all comes down to thoughtfully mapping out a data collection and management strategy that builds in flexibility from the start,” says Amir Malka, president and co-founder of Bioforum. “You need to put a lot of effort and accuracy into designing the study and at the same time be aware of the budgetary restraints.”
It’s critical for CRO executives, according to Malka, to understand a small biotech’s level of clinical trial expertise; its data strategy, plans, and assumptions, which may require modifications; the size and complexity of the study; and how to integrate all of the technologies involved.
The significance of correctly written and designed clinical trial protocols—targeting the correct data—is greater for emerging biopharma, executives emphasize. Bioforum, for example, works with sponsors throughout the clinical trial process to FDA submission, involving itself in developing the overall strategy for a new drug candidate, as well as addressing safety and efficacy issues that arise.
Hence, data must be properly integrated from all studies before regulatory filing, a complicated process that smaller companies often partner with CROs to support. Bioforum, for instance, has experience in several therapeutic areas, but its specialty is working with smaller biotechs as a full partner, du Plessis says. The company prides itself in its flat organizational structure, which eliminates layers of management between a customer and the Bioforum leadership team.
“Even though we are a global company, we can come down to a smaller company’s scale, and develop a good understanding of their specific needs” says Du Plessis.
This involves partnering from the beginning of a clinical development program and recognizing where the potential risk spots are, Malka adds. “Our goal is to build a strong, long-term relationship with sponsors that grows as they do; so building trust is a top priority for us,” he says.
According to du Plessis, Bioforum generally encounters three types of clients: those who do not know the specifics of how to collect and manage clinical trial data; those who have predefined concepts but who require more specific guidance; and those who are in the middle of conducting a trial and encounter significant issues.
“They need to think about which technologies they want to use to collect their data. And it must be the correct data in the correct format. This takes time, and if they don’t have a background in data, they don’t have a really solid understanding of what has to be done,” she says. “We’re not going to force them in any direction, but will give them an array of options. It’s about doing their homework for them and making their lives easier. At the end of the day, we want them to feel good about the data, and they should feel confident.”
“Our client base looks for us to supplement their capabilities,” Tara Franks, chief operating officer, Translational Drug Development (TD2), tells Applied Clinical Trials. TD2 is an oncology-focused CRO that also specializes in working with biotechs.
“Some biotech companies don’t have the resources of a larger pharma. They look to our team to fill in the gaps in their internal infrastructure,” adds Franks. “This may be the first time a client is developing a drug together as a team, whereas the large pharma companies do it on a regular basis and have an infrastructure and process in place. When we engage with smaller biotech companies, we help them develop their plan and process.”
CROs specializing in offering this type of tactical and strategic support along the path to potential regulatory approval is a big appeal to the smaller, clinical-stage biopharma.
“Scientists will publish in a high-impact journal, get some venture capital funding, and form a company,” says Stephen Gately, PhD, president and CEO, TD2. “But there’s a fairly significant gap between writing a paper and actually getting a drug approved. Companies are typically technology-heavy but not development-heavy.”
Emerging biopharmas need partners that can provide a vision and context of the regulatory realities inherent in drug development— and ones not distracted by “cool science.” Their audience now is the FDA and not a scientific publication,” says Gately. “They need a pathway to approval.”
TD2’s service focus in this area includes aligning the science of a client’s molecule with the regulatory requirements for clinical testing and potential marketability.
The company has a staff of experts who assist with and write the sections of an investigational new drug (IND) application related to the chemistry involved.
TD2 and others can solicit requests for proposals from institutions that manufacture drugs, select those vendors, and support and audit those companies. CROs focused on the emerging biopharma space often have expert toxicologists who can establish the requests for proposal, can identify the clinical studies absolutely necessary, the minimum number of trials required, conduct the studies, audit the sites, and generate output of all study results in a format suitable for FDA submission, says Gately.
“We’ve had the responsibility for 30 full oncology INDs where our team managed every single aspect and presented the technology to the regulatory authorities,” he says. “Some companies come with data from perhaps a single academic center, where they evaluated the technology against one particular tumor type. And they conclude that the therapy can be developed against that same tumor type. Those companies have access to capital. But they don’t always bring with that access a tactical and strategic approach.”
Joseph Constance is an independent writer and analyst based in New Jersey. He can be reached at email@example.com