CGT Manufacturers Face Variety of Commercialization Challenges

Sessions during the cell and gene therapy (CGT) track at the Reuters Pharma USA conference, held March 28 and 29 in Philadelphia, echoed much of the same advice for pharma companies commercializing one of these products. Starting the process early and collaborating with and forming partnerships with a variety of stakeholders are critical steps to success, multiple speakers emphasized.

Companies looking to bring a cell and gene therapy (CGT) to market should start preparing early on issues such as manufacturing and logistical matters, market access and patient access, advised Warner Biddle, senior vice president and global head of commercial for Kite Pharma, a Gilead Sciences, Inc. company. Kite has two chimeric antigen receptor T-cell therapies on the U.S. market: Yescarta (axicabtagene ciloleucel) — the second CAR-T to secure FDA approval — and Tecartus (brexucabtagene autoleucel).

He also advised manufacturers to “spend time on the system you will use to connect with patients” and providers, which for his company is Kite Konnect. “We did test runs” with authorized treatment centers, Biddle noted. “You have to focus on making sure this is flawless from the beginning.”

Marjan Shamsaei, vice president and head of commercial at Allogene Therapeutics — which is developing allogeneic CAR-T products — noted that even though his company has yet to have a marketed product in the U.S., it’s already dealt with reimbursement and manufacturing, and coordinated with authorized treatment centers and addressed the logistics of getting a product to patients.

Allogeneic CAR-Ts are “in a hybrid space,” he explained, in that there can be a product on a shelf that can be shipped anywhere in the world, “but it is also a living product” that requires a high-touch commercialization model. Preparation for launch “doesn’t start 18 to 24 months before your PDUFA [Prescription Drug User Fee Act]” date, Shamsaei maintained. “It starts much earlier than that.”

Asked by moderator Lung-I Cheng, vice president of cell and gene therapy at AmerisourceBergen, what the CGT space may look like in the next five to 10 years, Biddle asserted that “it’s an exiting time to be in CAR-T.” Companies are focusing on how to shorten the turnaround time, a process that normally takes weeks but has lengthened to months amid supply constraints. Companies also are investing in next-generation CAR-Ts, such as bispecifics, he noted. “I think we’re at a tipping point in the industry.”

“It’s not about allogeneic vs. autologous” therapies, said Shamsaei, but rather “how do we provide access to all” who need them? In addition, in the coming years, “I’d love to see the therapies get into solid tumors,” a hope echoed by other speakers at the conference.

Partnerships Across Industry Are Important

Many conference speakers emphasized the importance of partnerships within the CGT space.

Shamsaei observed that it was “good to see partnerships across the industry,” both between private companies and between private and public entities such as CMS and patient-advocacy groups. Partnerships also are important for monitoring patients after they leave an authorized treatment center, he stated.

Lynelle Hoch, senior vice president and cell therapy franchise lead for Bristol Myers Squibb, contended that it’s “really important that we partner across the ecosystem.”

Her company has two FDA-approved CAR-Ts: Abecma (idecabtagene vicleucel) via its Celgene Corp. division and Breyanzi (lisocabtagene maraleucel) through its Juno Therapeutics, Inc. unit.

Hoch noted that there has been some progress in developing CAR-Ts for solid tumors, citing gastric cancer in particular.

The big question around CAR-T “is can we make it durable?” In 2012, Emily Whitehead became the first pediatric patient to receive CAR-T, “and today she is getting her driver’s license,” pointed out Hoch. “I consider this a cure,” she said, “but this is the exception.”

She shared that Abecma had a “difficult launch,” as the wait list for it was “extraordinary,” and the company was under pressure from centers for treatment slots. It’s important for companies to provide clinical data to treatment centers in order to determine which patients are “best suited” for therapy.

To “deliver on the promise” of cell therapy, the industry faces three challenges, she maintained: operational, scientific and regulatory. Manufacturers need to “scale for 100% of patients,” and the “technology needs to equal the science.” Companies need to determine how they “can enhance efficacy” of the therapies, particularly as CAR-Ts expand into new indications, such as autoimmune disorders like multiple sclerosis and lupus, and drugmakers develop new next-generation agents.

Drugmakers need “a multipronged approach to meet these challenges,” Hoch insisted, one that involves stakeholders across the industry, including academic centers, health care providers, advocacy groups, caregivers and regulatory bodies.

“We are hope- and memory-makers,” she said. “It makes waking up very easy.”

Consistent Communication Is Needed in Evolving Market

Bill Nichols, senior vice president of marketing, sales, strategy and analytics for bluebird bio, maintained that prelaunch preparation should not be thought of as a blueprint but rather as “IKEA-like.” Much of the process has to do with “digitization,…audiences who expect information when they want it.”

The FDA approved two bluebird CAR-Ts last year: Skysona (elivaldogene autotemcel) and Zynteglo (betibeglogene autotemcel).

To engage effectively, “companies must consider how to engage with stakeholders when information is everywhere,” contended Nichols. “The issue of consistency is important.” Drugmakers should conduct stakeholder mapping and engage and “leverage the commercialization team so the right message is getting to the right stakeholder.” They also should clarify launch expectations.

“Be bold,” he advised. “The space you’re walking into does not exist.” That said, companies need to “plan for reality.…If you can’t pivot, you’ll lose.”

“What you think about cell and gene therapy is probably wrong because this is a constantly evolving market,” he maintained.

Asked about how his company is meeting demand, Nichols said that bluebird works with contract research organizations, a “constant process.…We want to continue to go as fast as possible,” but there are many steps in the process before a patient is infused. A further challenge he acknowledged is the ability to serve certain areas. For instance, sub-Saharan Africa has a high rate of sickle cell disease, “but the infrastructure isn’t there” to produce CGT.

When interacting with patients and caregivers, drugmakers must “be as transparent and honest as possible,” he stressed, adding that pharma cannot make assumptions about those stakeholders’ knowledge — or, more specifically, their lack thereof — around these agents. Companies “can’t assume they are any less intelligent than providers.…It’s a mistake to think this.” Rather, manufacturers must assume patients and caregivers “can make a decision on CGT in a heartbeat.”

On the possibility of standardizing CGT launch strategies, Nichols said that companies can build an approach informed by those of others, but he noted that even Kite’s two drugs had different strategies, so it can be “difficult to standardize.”

Over the next five years, he said he hopes access to these therapies improves. “My personal goal is that any patient who is healthy enough” to undergo CGT “can raise their hand” and have the opportunity for treatment.

Technology, Collaboration Are Critical for Commercialization

In a panel session on how to enable seamless CGT commercialization, Marie Muniz, senior director of marketing gene therapies for PTC Therapeutics, addressed the topic of how technology can be leveraged to identify patients within the ultra-rare disease space. Once a patient finally has a diagnosis for an ultra-rare disease — a process that often takes many years — technology can be used to “look back and see different misdiagnoses.” That data can be used to develop algorithms to “understand how patients are moving within the care system” in order to offer “interventional education points for providers,” among other opportunities. “Big data is wonderful,” as it can help reveal “trends in ethnicities,” as well as “where patients may be.” This information also can help determine the best way to communicate with certain communities, such as with bilingual opportunities.

Rita Johnson-Greene, chief operating officer for the Alliance for Regenerative Medicine and formerly with bluebird and Spark Therapeutics, Inc., explained that when the latter company launched Luxturna (voretigene neparvovec-rzyl), it was targeting ophthalmologists, “but we found many patients were located with primary care physicians” and sometimes nurses within emergency departments because the inherited retinal disease it treats “was being misdiagnosed.”

When most people have a medical issue, they go to their primary care provider, said Robert Sexton, vice president of program alliance and leadership at Mustang Bio, and “they languish there,” which can hinder getting an accurate diagnosis.

Muniz explained that if there is an ICD-10 code associated with a disease, for example, companies can use that to better understand a patient’s diagnostic journey, including what kind of providers patients were referred to and when, and then use that information to identify an intervention point.

When commercializing a product, “whether you are small or the biggest biotech on the planet, you have to start where you are,” stated Sexton. To do that, a company must evaluate its current state, including sales and operational teams, by conducting gap assessments and then develop the needed capabilities.

“The learning curve is tremendous,” he contended. And while employees may come into a firm with a variety of past experiences, they need to “throw those out” because they can’t assume that because they had an experience with one product, that it will be the same for another. They need to “respect and manage the differences.”

Allogene’s Shamsaei said the same thing during his session: A “good team…must learn and unlearn.”

The framework used for commercialization of traditional therapies “needs to look different for CAR-T,” asserted Marissa Cullen, director of CAR-T strategic planning & operations in oncology at Johnson & Johnson. “It’s a very different delivery model,” and there is a “real partnership between manufacturers and treatment centers” with CAR-T. In addition, while experienced centers will want to know how a new therapy differs from another treatment it has administered, newer centers “need a different level of training, education and handholding.…We need to meet centers where they are.”

When developing patient portals, “it’s probably a good idea to partner” with treatment centers, as “they are your primary customer,” advised Sexton. Companies should find people within their organization that can connect the front end, such as sales teams, with the back end, such as manufacturing. “Your portal is the least important part of your enterprise,” he said. “It is the things behind the portal that make the portal great.”

“You want the functionality to be intuitive and simple,” added Cullen. “If you know one treatment center, you know one treatment center.”

“Another consideration is when to train” treatment centers on a patient portal, said Johnson-Greene. Companies need to make sure that the centers have enough time to “react and respond to patients” but that not so much time elapses that they forget the training. It’s likely that only one or two people are doing intake at a hospital, she explained, but they are working with many different patient portals.

Cullen also noted that portals need to be flexible, as they may need modification. For example, what might be needed at launch may be different than what’s needed one year or two years postlaunch, or perhaps the patient materials a manufacturer launches with are not what the provider wants.

“If you have 100 certified treatment centers, you have to stay ahead of all of them,” Sexton noted. “There are a lot of moving parts,” and a lot of synchronization is needed.

Since each patient is unique, one attendee asked whether there is a role for white-glove personalized disease management. “Absolutely,” said Cullen. Added Muniz, “as different as treatment centers are, patients and caregivers are more different.” And Sexton noted that companies “have to manage a variety of personas” with different touchpoints.

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