Big Pharma Business Strategies

Scientific breakthroughs. Upcoming patent cliffs. Stagnant M&A. Lingering political unease. And a whole heaping dollop of uncertainty.

The ups and downs of the pharma industry last year have carried through into 2025, and although certain milestones like the outcome of the U.S. election have put some questions to rest, Big Pharma still faces a series of unknowns that have impacted their M&A strategies.

So far, reported earnings for the fourth quarter and full year suggest executives are going back to the basics to overcome the challenges of the year ahead, including a focus on smaller, more consistent deals as well as pumping up new meds to replace the losses of yesterday’s bestsellers. Here’s what some of those CEOs had to say in the last couple weeks.

J&J’s CEO provided insight into the company’s wide net for acquisitions, last year picking up Ambrx, Proteologix and Yellow Jersey Therapeutics, each with valuations of $2 billion or less. Last month, J&J kicked off 2025 with a $14.6 billion purchase of Intra-Cellular Therapeutics, larger than any pharma deal in 2024.

But is J&J aiming for more of those bigger deals as the year goes on? Not necessarily, according to Duato. Deals like the Intra-Cellular acquisition are opportunistic, he said, and while they create value as outliers, they don’t make up the company’s bread-and-butter business development strategy. In many ways, that reflects a wider trend in the industry, with pharmas placing smaller bets on earlier-stage assets that serve to build up a pipeline over time as opposed to in one fell swoop.

And as J&J’s pharma revenues feel the weight of competition to the blockbuster immunology drug Stelara, the pharma juggernaut managed to pour $17 billion into R&D last year and $32 billion into acquisitions in the last 12 months, which includes the buyout of Intra-Cellular. Those commitments illustrate the company’s full-steam-ahead approach to Stelara competition and other headwinds like Medicare redesign.

AbbVie faces some of the same headwinds as J&J in terms of overcoming the loss of a major blockbuster, but for the seller of the immunology flagship Humira, those winds blew a little harder — in 2022, Humira represented more than a third of AbbVie’s overall revenues, whereas in the same year, Stelara made up a much smaller portion of J&J’s total sales. With those big shoes to fill, the company has scrambled to bring patients over to its new meds Skyrizi and Rinvoq, and that bet is paying off, CEO Rob Michael said.

Skyrizi and Rinvoq are now expected to bring in almost $24 billion in revenue this year, Michael said on the earnings call last week, a growth of $6 billion from last year that would surpass Humira’s peak revenue of just over $21 billion in 2022 before competition became an issue.

Novartis faces a big patent cliff for its cardiovascular drug Entresto this year, and generic competitors will likely tear revenue down quickly. But the company has been growing its pipeline and, according to a report in the Wall Street Journal, looking to do more in obesity to fill those shoes.

But those opportunities won’t come easy, CEO Vasant Narasimhan said, and Novartis is likely to first stick with its growing expertise in RNA, cell and gene therapies. The Swiss drugmaker is working on its own obesity drug, and something would need to be very special to stand out as an acquisition target in that space, which is in very high demand.

That “replacement power” is what Narasimhan referred to in the company’s earnings report last week, particularly in clinical trial readouts that will be ready in the next few years. Meanwhile, the company is looking to achieve sales growth above 5% through 2029, outpacing generic competition impacts with a pipeline that provides “protection well into the 2030s,” he said.

Merck & Co. is facing a tough time in 2025 with a major headwind for sales of the HPV vaccine Gardasil in China and the question of incoming competition for the cancer drug Keytruda, which was the bestselling treatment in the world last year.

Merck had once expected to rake in $11 billion from Gardasil by 2030, but with low sales in China, that target has gone out the window, CEO Robert Davis said the Chinese landscape for the vaccine is “challenging,” but other aspects of the business will carry the weight. Particularly when it comes to Keytruda’s loss of exclusivity by the end of the decade, the company is looking at “a hill versus a cliff.”

In 2020, Pfizer achieved a major feat in developing the first approved COVID-19 vaccine, bringing billions of doses to the world. As the pandemic subsided, that star fell to earth as quickly as it rose. Now, executives believe that volatility is behind them as revenues stabilize. In the last year, the company actually reported better-than-expected sales for both the vaccine and the antiviral pill Paxlovid.

However, because COVID products aren’t expected to be the only contributor to Pfizer’s future success, the company is using its cash position to pump up the pipeline in oncology and other areas where it hopes to be an even stronger player in the years to come, Bourla said. CFO David Denton said on the call that the company could have between $10 billion and $15 billion in business development firepower in 2025 “if we chose to focus on that area.”

Manufacturing investments have taken center stage in recent years — from some pharma giants ramping up GLP-1 manufacturing capacity to meet soaring demand to other companies focusing on advanced capabilities that could ensure an adequate supply of vaccines.

With the spotlight on the industry’s need to increase capacity and make manufacturing more efficient,  Eli Lilly and Merck & Co. have partnered with Purdue University to launch the Young Institute Pharmaceutical Manufacturing Consortium, which will research and develop new production technologies.

“The consortium brings together companies invested in pharmaceutical manufacturing, with the goal of spanning the value chain: Big Pharma, startups, equipment manufacturers, instrument manufacturers, packaging companies, and venture capital, to name a few. Our initial focus will be on drug product manufacturing,” Elizabeth Topp, director of the Young Institute, said via email.

The collaboration also “underscores a commitment to onshoring pharmaceutical manufacturing while bolstering domestic production,” said a press release announcing the consortium. That could be especially important as new tariffs threaten to raise costs and exacerbate shortages.

Lilly has already put its money where its mouth is in that regard, saying it will spend $3 billion to expand a manufacturing facility in Wisconsin it bought in April and add new capabilities to produce injectable medicines. It also recently invested $9 billion in an Indiana manufacturing site and opened a new facility in North Carolina.

At the new Young Institute, companies will focus on experimentation.

“We hope that innovations from our consortium will make it into ‘real’ manufacturing facilities, though,” Topp said.

One major focus of the consortium will be improving aseptic processing technology, a key component of injectable drug manufacturing, through advances including AI, robotics and in-process sensors.

“Aseptic processing maintains a sterile, microorganism-free environment during manufacturing without using heat sterilization. It's particularly important for injectable liquid products, where sterility is an absolute requirement but where the drug could be damaged by heating,” Topp said. “These ‘sterile injectables’ include life-saving medicines like insulin and vaccines, and constitute most of the drug shortages in the U.S.”

Here, Topp explains more about the consortium’s potential impact on the industry.  

This interview has been edited for brevity and style. 

PHARMAVOICE: Let’s talk about how the consortium will leverage its manufacturing footprint. Will it include joint facilities and cost sharing? 

ELIZABETH TOPP: Yes, joint manufacturing facilities will be involved. We're working on renovating space at Purdue that will be a testing ground for new manufacturing technologies. It won't be operated under full regulatory approval (under GMP conditions), so we won't actually be making any drug products. We're very keen to have companies of all kinds join our consortium — proposals for joining by cost share, in the form of equipment donations or donations of computational resources, are welcome. 

How will these efforts eventually benefit the broader pharma industry? 

Member companies and the industry as a whole will benefit in several important ways. For example, our members will have the opportunity to develop new manufacturing technologies, and to drive the focus areas of the consortium's research efforts toward the critical pain points for the industry. Those efforts will involve collaboration with Purdue's outstanding faculty, which is rich in science and engineering talent in a strongly entrepreneurial environment.

In addition, members will be able to speak collectively to regulatory agencies, in the form of best practices papers and consensus standards for new manufacturing technologies, with greater impact than individual companies speaking alone. Our members will also develop a direct connection with a great talent pipeline in the form of Purdue students and will have the opportunity to help shape the type of education and training they receive. 

What will participation look like for companies in the consortium?

We have three membership tiers with a range of financial commitment and influence. The tiers have been designed to encourage participation by the full value chain, from multinational pharmaceutical companies to startups and academic institutions.

Will the consortium have an impact on the broader industry goal of onshoring more pharma manufacturing? 

It's a great question and we certainly don't have all the answers. Pharmaceutical manufacturing is global, with many key raw materials and drug compounds being produced in countries like India and China. Because it's less expensive to manufacture in those countries than in the U.S., offshoring has helped control overall manufacturing costs. Imposing tariffs may decrease the offshore advantage, but with the risk of greater overall costs, costs that will probably be passed on to consumers.

There is also considerable interest in onshoring pharmaceutical manufacturing to ensure that there's an adequate supply of critical medicines during pandemics or global conflicts. We hope that our initiatives to improve pharmaceutical manufacturing technology will help make onshoring achievable, and lessen the impact of tariffs, by improving efficiency, throughput, and supply chain management.  

Johnson & Johnson announced this year it would drop $14.6 billion on neuroscience company Intra-Cellular Therapies, reflecting a strong start to M&A this year and potentially signaling a surge that some industry watchers have been forecasting for 2025.

After a period of light M&A last year in which no transaction outside of GLP-1 manufacturing rose above $5 billion, and a wave of upcoming patent losses, pharma companies may now have no other choice than to pry open the purse strings.

“We’re still going to see this loss-of-exclusivity wave, and that puts pressure on the majority of the industry to be vigilant with how they spend and how they will be acquiring,” said Arda Ural, Americas life sciences sector leader at EY, who pointed out that the industry is in an ideal cash position to start spending on deals.

And while analysts have been “cautiously optimistic” for at least two years regarding a dealmaking upswing, and that has led to what Ural calls “optimism fatigue,” this year may be different because the pieces are falling into place.

“The industry has the capacity to afford it, and so we have continued optimism that we believe is different from the optimism of the prior two years,” Ural said.

Crunch time for M&A

While 2024’s deals pale in comparison to bigger mergers in previous years, pharma companies showed a willingness to look at earlier-stage deals that could pay off more handsomely in the long run, said Roel van den Akker, pharmaceutical and life science deals leader at PwC.

“When all is said and done, 2024 was a reasonable year for M&A in pharma and life sciences — we’re definitely down year over year in value, but volume was pretty decent with a good number of deals,” said van den Akker. “People have migrated to smaller transactions with a backdrop that was kind of unpredictable, but there are still significant [revenue] gaps moving forward, and companies are going to have to lean more heavily into M&A to make up those gaps.”

Pharmas looking to jump those gaps need to “take their foot off the brake and a little more onto the gas,” van den Akker said, pointing to more potential activity in the $5 billion to $15 billion range.

The strategy to transact earlier in a biotech’s R&D journey, along with the uncertainty of an election year, contributed to a year of smaller acquisitions with no deal rising above $5 billion, but that doesn’t mean pharmas have been lowering their standards, said Dan Chancellor, vice president of thought leadership at Evaluate.

“The ones that have been picked up are the ones that are really exciting, either best-in-class, first-in-class or offering new capabilities from a technological point of view, even though they’re earlier in the process,” Chancellor said.

He also noted the strategy could shift to bigger, later-stage acquisitions soon as the industry faces a wave of patent losses. 

“Between 2025 and 2029, we’re seeing $250 billion of revenue at risk, which is a huge amount to replace, and that will require more mature companies to navigate that patent crush,” he said.

The more a company faces near-term revenue challenges associated with incoming competition, the more likely it will engage in larger deals to offset future losses, Chancellor said.

“These are companies whose internal R&D and clinical trial results have underwhelmed, the companies that are essentially facing that they are going to need to plug a near-term hole,” Chancellor said.

Smaller deals aren’t necessarily a bad strategy for now though, van den Akker said. With lower execution risk and a more focused agenda on differentiated science, pharma could afford to be more selective while looking at these earlier-stage companies.

“Dealmaking is very focused on where larger acquirers see differentiation, clinically or otherwise, to complement their existing product portfolios — but if there’s conviction in the science, there’s no reason why a deal wouldn’t exceed the $5 billion range,” van den Akker said.

Even so, Big Pharma has been on a divestiture kick this decade with several big companies like J&J and Merck & Co. spinning off major business units to focus on core therapeutic areas.

“The conglomerate days are a little bit over, and companies really need to be focused,” van den Akker said.

Still, pharmas with cash to spend have waited out the U.S. election for a period of more certainty and the return to a valuation threshold that’s more appealing for the type of risk they’re willing to take on, Chancellor said. There are no sure bets, however, in terms of contributing factors, and every case is unique.

“M&A is just inherently volatile, and we’re careful not to ascribe too much importance to certain things when you will always have bumps and troughs on a cyclical basis,” Chancellor said.

In line for some larger deals are the usual suspects in the therapeutic areas of oncology and immunology, as well as growing areas of metabolic and neuroscience treatments, Chancellor said. Genetic medicines like cell and gene therapies and RNA-based programs are also on the rise, and rare diseases “are here to stay as a dealmaking opportunity,” he said.

A biotech bolus

The previous biotech boom at the beginning of the decade, during a time of low interest rates, fed into a period where companies weren’t as hard-pressed to differentiate themselves to gain funding, van den Akker said. Investments were widely available and less discerning than they are now.

“We’re living with a bolus of companies that went public or got funding in the 0% interest years that did not have the levels of clinical differentiation or were going into a crowded class with a me-too innovation,” van den Akker said. “That’s a nasty by-product of a low interest rate in a long-duration industry where people look at risks and rewards and returns 10 or more years out.”

Out of necessity, as those funds ran dry and competition became fiercer, biotechs have been more focused and disciplined, “which is something to be happy about,” van den Akker said.

IPOs faced a similar story with a boom in the early 2000s, van den Akker said, and a more conservative market now. But 2025 should be a healthy year for IPOs in the overall markets. Tech will lead the way, with some biopharma companies in the mix, he said.

“We’re on the up and up, with quite a few companies sitting in the green room, waiting for predictability and a stable backdrop, because in the IPO markets, timing is everything,” van den Akker said. Whereas cash runways dominated the conversation during more meager years, 2025 could portend a bigger focus on growth, he added.

New administration, new outlook

A new U.S. presidential administration could make a difference in 2025’s M&A markets, with a potentially less stringent FTC and interest rate cuts that have already begun.

The FTC, which took a stricter stance on anticompetitive behavior in the last few years, could begin to loosen under President Donald Trump, Chancellor said.

“Common conventional wisdom suggests the Trump administration would be less interventional with the FTC, which means we might see deals that tend toward the larger size, where previously there might have been anticompetitive risks,” Chancellor said.

A new administration also means an end to the uncertainty of a hotly contested election year. Knowing the way forward is important as companies grow their businesses, said van den Akker.

“The view is that predictability and stability in the environment creates clarity for dealmakers,” said van den Akker, noting that healthy GDP and decent unemployment, plus a more predictable and neutral interest rate, could provide a degree of certainty that has been lacking in the last few years.

And with the potential for more interest rate cuts on the horizon, more biotechs could be willing to jump into the IPO pool as well, Ural said.

“There’s a very clear inverse correlation between the cost of capital and IPOs, and when that window opens, there’s more opportunity in the market for capital moves,” Ural said.

Strategic R&D cuts have been a high priority for many pharma companies lately, from Moderna slashing R&D by 20% and discontinuing five clinical programs to Incyte eliminating several pipeline programs after a “strategic review.”

Although reevaluating and deemphasizing clinical programs is nothing new in biopharma, signs point to it being more widespread than a handful of companies doing business as usual. Analysts point to Charles River Laboratories’ staffing cuts and site closures as a sign of a decrease in demand for drug development services and a bellwether for the industry as a whole.

For the R&D programs that survive, the goal is to make them more efficient and cost effective than ever.

“There’s huge spend there,” said Bill Coyle, global head of biopharma at ZS, a healthcare consulting firm.

R&D efficiencies go beyond streamlining the pipeline to only include the assets that are most likely to succeed in the marketplace or using AI to boost efficiencies in drug discovery and trial design. This strategy should also include more practical, brass-tacks factors that impact the entire development process. Here are a few tactics that Coyle said will help companies get products to market more quickly.

Embrace human-centered trial design

Participating in a clinical trial can be burdensome for patients, which is why sponsors should design their trials with people’s real lives in mind and remove barriers to participation.

This could include compensating patients for transportation services and child and elder care, or connecting them with financial support groups. When looking to boost diversity in its clinical trials, Johnson & Johnson employed these kinds of tactics, Denise Bronner, the company’s director of diversity, equity and inclusion, told PharmaVoice earlier this year.

However, this approach can also extend to the way the trial is designed by using digitization and decentralization when possible and reducing the frequency of patient visits for assessments.

“If it's a blood draw, can you do it at home versus having to come in to the site?” Coyle said.

Human-centered trial design can also help boost ROI by making trial enrollment faster.

“If we increase the speed of enrollment, that is a big driver of the cost and the time to market, the time to which we get the data to submit,” he said.

Human-centered trial design also reduces patient dropout. Researchers estimate that it costs more than $6,500 to recruit just one patient, and replacing them adds to that expense.

Speed up decision making

One of the biggest inefficiencies in R&D is slow decision making, Coyle said.

Sponsors should decide quickly whether next steps are a go or no-go after a data readout. But that doesn't always happen. Instead, they take too long moving from proof-of-concept to phase 2 and phase 3.

“They're big, important, expensive decisions,” Coyle acknowledged. “But I think there's a little bit of time lag there sometimes. How do we more rapidly make those decisions?”

One way is by thinking through decisions early. As trials move into later stages, companies must determine whether the data supports a marketable product, as well as shore up their phase 3 trial design and study endpoints. Instead of waiting for data readouts to start that decision-making process, companies can think ahead and map out different actions based on possible phase 2 outcomes.

“Being very clear on those as you're going through phase 2 [is important] so when you see the readout, you're able to act quickly,” Coyle said.

He also warns executives against fighting too hard for a lagging asset because they’re wedded to a therapeutic category or were involved in the asset’s identification or purchase.

“Some of the human elements do get involved in these decisions, which make them slower to negotiate and move through,” he said.

Be smart about site selection

Sponsors often choose trial sites they have an existing relationship with. But making that the sole or most important criteria is the wrong strategy. Instead, companies should choose the most productive trial sites by leveraging data about prior performance, speed of enrollment and whether they hit their enrollment targets, Coyle said.

Sponsors should also look for sites that will provide the appropriate clinical trial diversity and that are geographically relevant to the therapeutic category based on patient data.

“We have to be thinking about the prevalence of the diseases,” Coyle said. “Different diseases might have different prevalence drivers and be more prevalent in different areas.”

One of the most difficult aspects of developing treatments for Alzheimer’s disease is understanding the mechanisms of neuron death amid amyloid plaques, tau tangles and other forms of toxicity that are all engaged in a complex web.

While amyloid plaques have been the target of choice for approved therapies like Kisunla from Eli Lilly and Leqembi from Biogen and Esai, researchers are still on the lookout for deeper connections to treat the disease earlier and more effectively.

Apart from the amyloid hypothesis, tau tangles have been shown to more reliably predict which parts of the brain are affected by Alzheimer’s disease, potentially leading to treatments that could make a difference in disease progression.

“I would love to know why neurons die,” said Fiona Elwood, vice president and disease area leader in neurodegeneration at Johnson & Johnson Innovative Medicine. “We still have a lot of unknowns. Why does amyloid trigger tau aggregation and the spread of tau through the brain? If we knew the mechanism that links amyloid to tau, that could be an opportunity to intervene at this critical acceleration point in disease progression.”

J&J recently picked up a fast-track designation for posdinemab, a monoclonal antibody that targets tau tangles, adding to the company’s Alzheimer’s roster that also includes a fast-tracked anti-tau immunotherapy called JNJ-2056. Both candidates are entering phase 2b trials, with posdinemab’s fully enrolled.

“We’re excited about the potential of posdinemab because it’s tau that predicts disease progression in patients,” Elwood said. “Whilst amyloid may be more of a triggering factor, tau appears to be the driver of neurodegeneration and cognitive decline.”

Still, Alzheimer’s research isn’t a zero-sum game — both options could be useful in different patients or those at a different point in their disease.

“This is a huge population with great unmet need, and there’s going to be opportunity for multiple mechanisms of action,” Elwood said.

Reprioritizing the pipeline

J&J has been in the Alzheimer’s R&D space for more than 30 years, and what helped the company turn a corner was the discovery of biomarkers to determine which patients will benefit most at the right times. But the disease has been tricky, and the company had to trim the neurodegeneration pipeline last year to keep resources flowing to more likely prospects.

The most high-profile of these cuts was the discontinuation of the mid-stage Alzheimer’s candidate seltorexant, which was being studied as a potential treatment for the agitation and aggression that patients (and their caretakers) often contend with. J&J will continue to pursue seltorexant as a treatment for depression and insomnia.

But Elwood noted that the pipeline adjustments give the company a chance to redouble efforts on therapies like posdinemab.

“We have to do this all the time,” Elwood said. “We’re making sure to channel our resources to the drugs that are most likely to have an impact on patients, and [posdinemab] is targeting a new mechanism of action with the goal of disease modification.”

Posdinemab is unique in that it targets tau outside of the neuron cells — traditionally, tau is thought to be inside cells while amyloid builds up between neurons. The extracellular phosphorylated tau was discovered about 10 years ago as a potential means by which the tangles proliferate in a patient’s brain, Elwood said, noting that posdinemab has been shown to block that spread.

Tau-targeted therapies have stumbled in the clinic before, though. From Biogen’s gosuranemab to Lilly’s zagotenemab to Roche and AC Immune’s semorinemab, the industry’s perseverance has been tested by many failures.

J&J stuck with tau for its remaining pipeline candidates in Alzheimer’s because researchers like Elwood believe the protein exhibits the most potential in cognitive decline. While approved therapies like Leqembi and Kisunla have demonstrated an ability to reduce amyloid in the brain, their clinical effectiveness has been called into question.

“These [anti-amyloid therapies] are great because they’re the first disease modifying therapies, and they show it’s possible to slow disease progression in Alzheimer’s patients,” Elwood said. “Posdinemab is different because it targets tau, which correlates really well with cognitive decline — this is why we think tau is a great target and why we’ve invested in these two therapies.”

An intermediate start

With posdinemab, J&J is focused on patients in a particular sweet spot for therapeutic intervention. Using a PET scan, they determine which patients have enough tau to measure the spread, but not so much tau that intervention could be too late.

“We’ve used tau PET and novel analytic methods to enroll this intermediate level of tau, and we’re the first tau monoclonal antibody to use that precision approach,” Elwood said. “We’re enrolling a patient population where we think we’re most likely to match that mechanism of action.”

Although competing pharma companies are operating in different ideological camps — amyloid, tau and otherwise — Elwood said there is a sense that everyone is also working together against the disease.

“We have to recognize what a radical change these new amyloid removal therapies represent for the field — if you were a patient who was experiencing cognitive decline five or even three years ago, what would your diagnosis pathway be?” Elwood said. “No blood tests, costly and invasive diagnosis procedures and only a symptomatic therapy along with the phone number for the Alzheimer’s Association — now we’re talking about well-based biomarkers to diagnose patients.”

The slow uptake of anti-amyloid drugs hasn’t deterred J&J’s own efforts, Elwood said, because posdinemab could enter a changed landscape in the event of an approval down the road.

“I don’t think it’s that surprising we’re seeing slow uptake because the whole system has to change in order for patients to access these therapies,” Elwood said, pointing to difficult diagnosis and treatment schedules, as well as side effects that could scare off payers. “These are meaningful therapies that represent meaningful change, but there’s still a huge opportunity to improve on them from the perspective of efficacy, safety and convenience.”

As for J&J’s other Alzheimer’s candidate JNJ-2056, Elwood said the convenience of an intramuscular immunotherapy against the disease could be “a game-changer for patients,” particularly those in an earlier stage of the disease.

“We want Alzheimer’s to be ancient history,” Elwood said. “The way to go about that is to identify patients as early as possible and target key drivers of disease like tau, as well as other mechanisms that can stop patients from ever moving to that place where they experience symptoms and cognitive decline.”

More and more pharma companies are looking to get under patients’ skin. 

From weight loss to cancer drugs, subcutaneous injections are popular with patients for their convenience, potentially freeing them from cumbersome intravenous infusions. Subcutaneous versions of existing drugs also benefit pharma companies by maintaining drug exclusivity. 

For example, the patent on Merck’s blockbuster Keytruda expires in 2028, but the investigational subcutaneous version of the drug, if approved, could retain patent protection, insulating the company from anticipated revenue loss. Recent oncology approvals include subcutaneous versions of Opdivo from Bristol Myers Squibb and Tecentriq Hybreza from Roche’s Genentech. 

The option is also appealing outside of cancer. 

Johnson & Johnson introduced its long-time IL-23 inhibitor plaque psoriasis and psoriatic arthritis drug Tremfya to the ulcerative colitis space in September. The approved regimen includes an IV induction phase and subcutaneous maintenance treatment, but J&J is now seeking approval for a fully subcutaneous induction option, which could make Tremfya the first drug in this class to offer an IV-free treatment pathway for UC patients. 

Other IL-23 UC options, which include Eli Lilly’s Omvoh, the first in the drug category to hit the market in 2023, and AbbVie’s Skyrizi, approved for UC and Crohn’s disease in June, only offer subcutaneous maintenance treatments, giving J&J a potential leg up in the space.

Responding to patient preference

Chronic illnesses like UC are prime targets for subcutaneous options because they minimize the daily disruptions associated with keeping these diseases in check. 

“[For] a younger patient, busy at work, needing to manage the hectic demands of family [and] professional life, intravenous drug infusion could really interrupt the flow of a day,” said Dr. Esi Lamousé-Smith, vice president and gastroenterology disease area lead in immunology at J&J Innovative Medicine. “A subcutaneous option makes meeting the demands of life while also managing disease a little bit easier.” 

J&J hopes data from its phase 3 study will convince the FDA to approve the new UC induction therapy. The drug met its primary endpoint, achieving patient remission and all secondary endpoints. 

Overcoming challenges 

Another reason subcutaneous options are on the rise is improved drug delivery technology and scientific advances in drug formulation, such as ensuring the proper drug concentration and stability. Some molecules still are more difficult to convert than others, Lamousé-Smith said. 

“There’s only so much in terms of volume that can be administered in a subcutaneous option,” she said. “So, each of those becomes potential challenges that need to be addressed and overcome from a scientific and pharmacologic perspective.” 

Manufacturing can also be a hurdle. Attempts to formulate a subcutaneous version of Rybrevant for non-small cell lung cancer ran into trouble recently due to problems at one of J&J’s manufacturing facilities.

Developing a subcutaneous option requires proactive planning to determine the best way to deliver the drug — using a syringe or specialized device — or to train patients in self-administration. 

“When people are developing subcutaneous treatments, they're thinking about all of these questions, addressing these questions, and then coming up with different ways to solve the problem,” Lamousé-Smith said.

However, if companies can overcome the challenges, the end result can pay off. 

“That has been one of our goals to provide both versatility and optionality for both physicians and patients,” she said.

GSK’s antibody-drug conjugate Blenrep looked like a breakthrough in multiple myeloma when it was approved in 2020, even as a fifth-line treatment for the difficult blood cancer. Just two years later, though, the drugmaker had to pull Blenrep from the market due to a failed confirmatory trial.

But GSK didn’t give up on its promising ADC, which targets the B-cell maturation agent (BCMA) commonly found in patients with multiple myeloma, and the company yesterday revealed overall survival data that could set Blenrep up for a blockbuster comeback. In combination with chemotherapy and a steroid, Blenrep reduced the risk of death by 42% compared to Johnson & Johnson’s standard-of-care, second-line treatment Darzalex. The results were revealed at the American Society of Hematology annual meeting.

Blenrep’s potential re-entry into the multiple myeloma space comes when the market has plenty on the horizon, with cell therapies and bispecific antibodies poised to make a bigger splash in years ahead. 

Still, GSK is confident it has a game-changer on its hands.

“We’ve seen a lot of great progress being made in multiple myeloma over the past several years, which is really important for patients,” said Dr. Hesham Abdullah, global head of oncology R&D at GSK. “When you could potentially be improving five-year survival rates for patients, you’re doing something that is really impactful … and [these studies], along with this overall survival data, provide an important data point and body of evidence supporting the use of Blenrep-based combinations moving forward for patients with relapsing multiple myeloma.”

A changing landscape

When Blenrep won an accelerated approval in 2020, it was the first BCMA-targeting treatment to get the regulatory go-ahead. But pharma has been busy with multiple myeloma in the years since then.

Approvals for BCMA-targeting cell therapies like Abecma from Bristol Myers Squibb and Carvykti from Johnson & Johnson, as well as bispecific antibodies such as J&J’s Tecvayli and Pfizer’s Elrexfio, have entered the scene — while Blenrep has been sidelined.

For Abdullah and his team at GSK, it took resilience to go back to the drawing board and prepare the drug for its next stage, all while learning from the past.

“I reflect on this a lot, and this journey has been one of those unique experiences that drug developers don’t often go on,” Abdullah said. “We looked really closely at the data … and part of it was going back and saying, ‘How do we look at the mechanism of action of this drug?’”

That meant finding the silver linings, like a 41% response rate in patients who were already heavily pre-treated and a response duration of more than 25 months — a result that was “probably unheard of for an antibody-drug conjugate in a late-line patient population,” Abdullah said.

Those takeaways set the stage for two head-to-head late-stage studies: DREAMM-7 against the Darzalex combo, which led to the most recent survival data, and DREAMM-8 against a combo with the older drug Velcade, which earlier this year demonstrated a 48% reduction of disease progression or death.

“We were very confident in the outcome of the DREAMM-7 and -8 results,” Abdullah said. “We had great support and partnership of key external experts and colleagues from around the globe that told us to continue.”

Blenrep also has an advantage over other BCMA-targeting drugs, particularly in terms of hospitalization, the long turnaround times associated with CAR-T cell therapies and some infection-related side effects of bispecific antibodies, according to Dr. Maria-Victoria Mateos, lead investigator of the DREAMM-7 study.

When it comes to Blenrep, Mateos called the results a “potential paradigm shift.”

‘A hard road’

Before Blenrep reaches blockbuster potential, GSK will need to find the right dosing regimen for different multiple myeloma patients, said Citeline senior analyst David Dahan. Some physicians might be cautious about toxicity, he said, particularly with side effects that induce blurred vision and cause about 10% of patients to discontinue use.

“[GSK] is going to have to show some new clinical data showing a safer dosing regimen,” Dahan said, pointing out that reduced dosing could have the same efficacy — a “less is more” approach. “Is it going to reach blockbuster status? It may eventually, but it is going to be a hard road.”

Abdullah said GSK is exploring the dosing options.

“[We are] looking at lower doses, more extended schedules — our focus is continuing to better enhance the overall profile of Blenrep, especially as we start thinking about moving into front-line patients,” Abdullah said.

With an expected decision from the FDA next year, the company has forecast peak annual sales of $3.8 billion.

And although bispecifics are currently approved in much later lines of treatment, they could start moving up the line, driving more competition against Blenrep, Dahan said.

Still, Blenrep could become the flagbearer for other medications in GSK’s pipeline.

“As we’re rebuilding the pipeline and continuing to expand, we’re also looking at … other therapeutic modalities that we’ll be bringing into our repertoire, including in multiple myeloma,” Abdullah said, adding that this could include “a next generation of antibody-drug conjugates.”