Years ago, in the era of small-molecule, mass-market pharmaceuticals, the name of the game was market share. Companies were judged on how quickly, and how convincingly, they dominated the market for a therapy class. Field sales reps were incentivized on new prescription (NRx)—the volume of new patients that start on a drug—and there were stories about sales reps so quickly offering price discounts that the drug was actually a loss leader for the manufacturer.

Now, with the rise of specialty pharmaceuticals and rare-disease therapies, the emphasis is on gross-to-net (GTN): the ability to retain as much of a drug’s offering price as net revenue to the manufacturer. An industry where nearly half of revenue comes from 2%-3% of the patients treated (the rest of spending being non-specialties, or low-margin generics) is, in a word, a distorted market. That warped market puts an emphasis on a crucial management function: market access.

Market access has become a catchword over the past decade in parallel with the rise of another factor in drug commercialization: the dominance of pharmacy benefit managers (PBMs). This year, according to estimates from IQVIA, 52% of the wholesale acquisition cost (WAC, generally considered the best approximation of “list price”) of drugs sold in the US is taken up by rebates to PBMs and other payers—and this will continue growing over the next four years. Manufacturers provide rebates to PBMs with the expectation of favorable placement on the PBMs’ formularies, which, in turn, increases the likelihood that patients will receive that therapy.

PBM rebates are the dominant factor affecting GTN revenue; nevertheless, as much as 35% of patients don’t fill their prescriptions, mostly due to the price the patient sees at the pharmacy counter. Thus, rebates don’t solve the market access question. The manufacturers’ response to that is to provide a coupon or voucher to the patient, and some $50 billion is spent on that effort. PBMs have responded by limiting how much of the coupon value gets to the patient (the term of art is coupon accumulators or maximizers), so yet more revenue is lost to the manufacturer.

There are additional obstacles: the use of prior authorization letters, which put a burden on the prescriber to clear the way for the patient to receive a drug; limitations on which pharmacies are able or willing to dispense the drug; or outright PBM “exclusion lists” (which have grown from a handful 10 years ago to over 600 in 2024). Exclusive or limited-distribution specialty pharmacies present their own problems, representing additional costs, accessibility questions and the like (on the other hand, they also represent one of the best ways to get hands-on service for complex drug therapies).

Government pricing

Most of the preceding refers to commercial insurance plans, and the PBMs most often are service providers to the health insurance providers for employers (and the biggest PBMs are now subsidiaries of these insurance companies). A whole other world of complexity enters with government provided health insurance: Medicare, Medicaid, TriCare (for the military); and a variety of interrelationships with individual states.

TriCare and, to a certain extent, Medicaid, have been subject to negotiations over drug prices, with mandated discounts for many patients. With passage of the Inflation Reduction Act of 2022, a long-sought goal of healthcare experts was achieved: negotiated pricing for a limited number of branded drugs. That negotiation is set to begin next year, with additional drugs added in future years. Meanwhile, the Trump administration is shaking up the government-pricing scene, first by negotiating discounted prices for the popular GLP-1 obesity drugs, and second by threatening to impose a “most-favored nation” (MFN) price for other drugs, based on what those drugs cost in other countries.

All that being said, the government program most alarming to the industry today is the continued growth of the 340B discounting program, which allows “covered entities” (healthcare providers such as hospitals that provide care to indigent patients) to substantially discount what they pay for drugs. From a small start in the early 2010s, the program has grown to cost manufacturers $147.8 billion in 2024, and has been growing at double-digit rates for years.

Industry groups such as the Pharmaceutical Research and Manufacturers of America have been protesting inequities in the program more and more loudly; on the flip side, the American Hospital Association says the discounting is justified for indigent care, while also freely admitting that “Without the financial support from the 340B program, communities in need across the country could lose access to valuable, lifesaving care.”

Integration is the goal

With all these revenue sinkholes growing, it’s no wonder that corporate executives are feeling increasingly defensive.

“It’s not surprising that gross-to-net has become a concern at the C-suite level,” says Maria Whitman, global head of commercialization at ZS Associates. “Every company has now realized GTN is no longer optional. It informs smarter contracting, it informs pricing, it informs affordability decisions.”

Going further, Whitman says that the overall topic of market access has expanded, going well beyond payer contracting to include field sales, health economics, and even reaching back into clinical decision-making. There should not be an approach of a “point solution” to access questions.

This scenario will require a much broader perspective than the operational managers of pharma are accustomed to.

“In my numerous industry presentations, I’ve asked from the stage, ‘How many of your brand managers can articulate what gross-to-net is?’ and the response has been, ‘very few,’” asserts Bill Roth, general manager and managing partner of IntegriChain’s consulting business, and a Pharmaceutical Commerce editorial advisory board member.

Integrichain started 2025 with the launch of the ICyte Commercial Data Suite, a “revenue optimization” platform that provides highly detailed analytics, including data aggregation, master data management, channel, and patient-journey analytics. The analytics also form the backbone of a regulatory, compliance, and controls function.

Model N, an IT company based in Redwood City, CA, pioneered what it called “revenue management” (more or less synonymous with GTN) over a decade ago, and now processes data for many of the largest pharma companies. Jesse Mendelsohn, senior vice president, says that contracts between pharma companies and payers generally run two to five years, and usually have built-in specifications offering periodic reviews (by the buyer or the seller).

“Our pharma clients are usually monitoring the agreements to ensure that they are meeting internal targets.” The current wave of “value-based” contracts—designed for expensive specialty treatments—are especially challenging: because reimbursement is based on outcomes, anonymized patient data needs to be evaluated and issues like the completion of adherence programs need to be verified. “We’ve built our software platforms to be very flexible to incorporate new or specialized data sets,” Mendelsohn notes, adding that compliance with complex state and national legal requirements is an equally important goal.

Furthermore, Model N is already gathering much of the data required for calculating reference pricing (in cases where a national payer uses this system) or for potential MFN reporting could come into effect in the US.

A variety of other organizations have developed IT systems and services to manage access and the broader goal of getting drugs to patients. Some examples:

IQVIA. Known as a market leader in gathering sales and prescribing data for pharma clients, has developed a range of IT tools and services for what it calls “Connected Intelligence.” Services include strategy consulting and data analytics as well as GTN planning, rebate validation, and state-level price-transparency reporting. The company unifies these and related services in a Market Access Center of Excellence.

Luke Greenwalt, former lead of the center and now VP, US thought leadership and innovation, illustrates the problems with a narrow focus on payer relationships. “A recent client launched a specialty product and generated a certain demand for it. But following through on that demand and finding how many of those patients were still persistent (i.e., on therapy) 12 months later dropped the figure to 4%.” This shows that if “you get formulary coverage, but it has prior authorizations or it has step edits in it, or it has line of therapy considerations for it, there’s a lot of leaky points for this. That quality of access really becomes an important piece to consider,” he concludes.

Greenwalt says that IQVIA espouses a “total cost of access” calculation that would include rebates and any GTN deductions (such as 340B programs or upfront discounts to wholesalers), plus co-pay offsets. “The goal is to manage these holistically, thinking about trade-offs as you move through the process, and [seeing] what the effect is on your bottom line.”

ZS. According to Whitman, it is a given today that pharma companies need to expand their scope beyond contracting details and GTN computations. The company espouses something of a bottom-up approach of first aligning workflows to enable automation, and then applying a host of artificial intelligence (AI) tools—specifically, agents—to speed up analysis and decision-making.

“Even before you talk about technology, you should ask, what is the end-to-end process here? Where are the places you can cause a real impact? Then, let’s build out the data analytic readiness infrastructure and all the right places to use AI so that you can mitigate [revenue leakage],” says Whitman. When done right, she adds, the workflow automation enables looking at the entire funnel, from point of manufacture to point of patient engagement.

Whitman says that it builds AI systems and agents for point solutions to business management problems, but is also flexible to make use of clients’ own AI efforts, and a wide array of third-party software providers. Two examples of how this has worked successfully for clients are an automation system for copay fraud detection; and a related system for rebate anomaly detection. In the former case, 70 pharmacies were flagged for fraud, saving $25 million; in the latter case, irregularities in rebate claims, such as duplicate discounts, were identified that resulted in a one-year savings of $40 million.

“What this means is that not only do we save those expenses, but we’ve gotten smarter on how to find patterns across contracts, or analyzing pricing sensitivity in contract operations,” she says.

This level of AI sophistication is undoubtedly a heavy lift for most pharma companies. Whitman says that the first wave of AI applications has been in document generation—cutting the time needed to produce meaningful reports from data. The second wave is to find efficiencies in business functions (such as the fraud detection in co-pays or rebates). The coming third wave is achieving meaningful effectiveness, making the overall process more aligned to creating value for the enterprise.

Eversana. Eversana has built up a substantial business in what could be called “commercialization in a box,” in that it offers pharma clients—usually small-to-midsize companies—clinical and commercial services, including field sales, contract management, logistics, and a specialty pharmacy to deliver directly to clinics or patients. A robust patient-support system can also be included. The company announced a string of such commercialization projects, including with Shorla Oncology, OS Therapies, Iterum Therapeutics, Precigen, Inc., Citius Oncology, and OWP Pharmaceuticals, just this year.

Direct to patient

Eversana considers itself well-positioned to take advantage of a growing practice in pharma commercialization—direct-to-patient (DTP) services. The practice has been tried at various times in the past, but took a noticeable jump forward in the industry when Eli Lilly announced LillyDirect to distribute its Zepbound obesity product in 2024. Telehealth interaction with a prescriber is combined with a cash-pay program to, in effect, sidestep PBMs, insurance obstacles (if present), and wholesaler involvement.

According to Faruk Abdullah, chief business officer, the company’s DTP program is “a platform solution that allows manufacturers to offer cash pricing or even covered pricing in a digitally convenient manner where a patient can be able to go through digitally, engage with a physician, figure out their disease, get a prescription, have their benefits verified, their prior authorization verified, and get their product at the lowest cost possible already automated through their benefit and shipped to their local pharmacy or to their home, all automated under our direct platform.”

Abdullah stresses that a DTP program is more than a telehealth connection and mail-order pharmacy; a well-run program should include “staying with the patient throughout the life cycle of their experience on a brand all the way through, making sure they’re adherent and keeping up with them.” Eversana provides a white-label “skin” to the online portal, so that the program retains the manufacturer’s branding, while also providing the behind-the-scenes functionality.

Like others in the commercialization services field, the company is plugging away at AI implementations, an effort that Eversana calls “pharmatizing” AI. The company has a relationship with Google (and Google’s AI product, Gemini) for an AI-based marketing agency, as well as a collaboration with Amazon for a service called Orchestrate MLR, for medical, legal, and regulatory report writing.

Knipper Health. Knipper Health, benefiting from a mid-year investment by private-equity firm Frazier Healthcare, is also jumping on the DTP bandwagon. The company has a long history in providing sample and marketing-materials delivery to HCPs; now, it has built out a DTP platform that includes its in-house pharmacy plus linkages to copay programs and live patient support.

“We have been able to show a significant improvement in patient conversions over the traditional retail pharmacy channel,” says Willis Chandler, CEO. “In some cases, up to 90% conversion versus 50% that has been estimated in retail. This is a huge win for our pharma partners.”

The Big Four consulting/accounting firms, Accenture, Syneos Health, and Clarkston Consulting, as well as numerous other consultants are positioning themselves to help pharma companies navigate the changing commercial arena. From the look of things, the pharma industry will need all the help it can get in dealing with the increasingly hostile commercial space of the next few years.

— Nicholas Basta is Founder and Editor Emeritus of Pharmaceutical Commerce