Commercialization

U.S. Humira sales fell 40% year over year during the first three months of 2024, to about $1.8 billion, as biosimilar copycats put pressure on AbbVie’s top-selling drug, the company said April 26.

The declines were “in line” with what the company had anticipated for its inflammatory disease drug, AbbVie commercial chief Jeffrey Stewart said in a call with investors. Humira now faces 10 copycat competitors in the U.S., the first of which launched Jan. 31, 2023.

Stewart said the company also expected a recent decision by CVS Health, whose pharmacy benefit manager is the country’s largest by prescription claims, to remove Humira from its national pharmacy effective April 1. Although that has meant Humira’s market share dropped from 96% to 81% over two weeks, Stewart said some of the shift went to other branded medicines, like AbbVie’s products Skyrizi and Rinvoq.

AbbVie’s post-Humira future is becoming clearer. Richard Gonzalez, the only CEO the company’s ever known, is handing over the reins effective July 1 to chief operating officer Robert Michael. The executive team has nearly finished navigating Humira’s loss of market exclusivity and AbbVie’s next challenge is growing its newer slate of drugs.

But questions remain about how much revenue AbbVie can still wring from Humira, which topped out at $21 billion in global sales in 2022, as well as how quickly it can be replaced by revenue from Skyrizi and Rinvoq, which treat many of the same conditions Humira does.

Skyrizi and Humira had nearly equivalent global sales in the first quarter, at $2 billion and $2.3 billion respectively, while Rinvoq brought in $1.1 billion. The newer drugs are growing quickly, too — Skyrizi sales rose 48% and Rinvoq 59% over the first quarter of 2023.

CVS’ decision to exclude Humira does raise some doubt over how well sales will hold up in the U.S., especially if other pharmacy benefit managers follow that lead. Sandoz’ Hyrimoz, which benefits from an exclusive contract with a CVS subsidiary called Cordavis, represented 15% of the total prescriptions for adalimumab, Humira’s scientific name, for the week ending April 12, according to analysts from Deutsche Bank.

That number held steady the week ending April 19, those analysts wrote. However, Alvotech and Teva announced a deal for their new biosimilar Simlandi, which mimics Humira’s most popular formulation and can be directly substituted at the pharmacy. “It's hard to rule out” a similar strategy to “rapidly gain share,” the Deutsche Bank analysts write.

Stewart said AbbVie doesn’t expect “widespread” exclusions, however.

“If we look through the rest of ‘24 we have very solid contract with the payers,” he said. “Remember that these payers can add biosimilars at parity, whenever they choose to [as they did] last year, in the middle of the year, and that's really not different [this year].”

At the start of the last decade, big pharma was getting smaller. Blockbuster medicines that had fueled years of growth were losing patent protection, exposing the industry’s largest companies to generic competitors. The resulting impact was so substantial it temporarily stalled the relentless upward march of U.S. drug spending.

Today, big drugmakers are facing an even larger “patent cliff,” with more than $200 billion in annual revenue at risk through 2030. But this time around, many of the brand name drugs losing market exclusivity are biologic products, manufactured from living cells, rather than the chemical pills that previously dominated the ranks of pharma top-sellers.

These biologic drugs, like AbbVie’s anti-inflammatory treatment Humira and Merck & Co.’s top-selling cancer medicine Keytruda, will face competition from so-called biosimilar drugs that, unlike generics, may not be as easily substitutable. Still, it will be a treacherous period for drugmakers to navigate, as they will need to replenish their research pipelines and carefully manage new product launches to replace lost revenue.

“This is of tectonic magnitude,” Arda Ural, health sciences markets leader at the consultancy EY. The looming patent expirations "capture most blockbusters," he added.

Besides Humira and Keytruda, drugs like Bristol Myers Squibb’s immunotherapy Opdivo, Johnson & Johnson’s immune disease medicine Stelara and Regeneron’s eye treatment Eylea will reach the end of their patent protection this decade.

The launch of Amgen’s copycat version of Humira in January was a start of sorts for this looming industry-wide patent cliff. Half a dozen other Humira biosimilars arrived by mid-year. As a result, U.S. sales of the drug, which totaled $18.6 billion in 2022, are predicted to steadily shrink.

A different sort of cliff

The pattern of sales decline for Humira and other blockbuster biologics like it is expected to be different for several reasons, though.

Many biosimilars won’t be interchangeable, or directly substitutable, by pharmacists, for example. Physicians, meanwhile, may be reluctant to switch patients who are stable on the branded drug, meaning that initially it will be newly diagnosed patients with chronic diseases who are most likely to receive biosimilars. And because biosimilars are more expensive to develop and make, their manufacturers won’t be able to afford cutting prices by nearly as much as with generic pills.

“If you track the sales of a typical small molecule that goes generic it really goes off the cliff — 80% of the market can be gone in 30 to 90 days and the price goes down even more,” said Richard Kelly, a senior partner with the law firm Oblon, McClelland, Maier & Neustadt who specializes in life sciences intellectual property.

“[Biosimilars] have to be sold,” he added. “[Salespeople] have to go around to the doctors to sell a drug. It’s just another product in the detail-man’s bag.”

Take the statin Lipitor, once the world’s most lucrative drug. Sales fell from nearly $11 billion in 2010, the year before it faced generics in the U.S., to $4 billion in 2012. Pfizer’s overall revenue fell from $68 billion to $59 billion over the same period.

In the case of Humira, the fall is expected to be more gradual, with the company forecast to retain more than one-third of its 2022 U.S. revenues in 2024 and hold onto more than $2 billion through 2030, according to Evaluate Pharma.

The impact will be felt, nonetheless: AbbVie and analysts alike expect company-wide revenue to fall for at least a year because of Humira competition. And AbbVie executives recently indicated sales are likely to be sluggish in 2024, too, walking back earlier predictions that the company would see a return to growth then.

Humira’s sales erosion will be closely watched throughout the industry as executives and investors try to understand the long-term effects of biosimilar entry. Early biosimilars didn’t impact prices the way that payers and lawmakers had hoped, in part because there weren’t many of the copycat drugs. (While 42 biosimilars are now approved in the U.S., only a little more than two dozen are available on the market.) Branded drugmakers also successfully used contracts and rebates to stave off competition.

However, analysts and industry experts believe the sheer number of Humira copycats and the entry of interchangeable products will allow them to take share from AbbVie.

The chief question facing AbbVie is how quickly it can recover through two replacement products: Skyrizi for psoriasis and Crohn’s disease, and Rinvoq for rheumatoid arthritis and several other inflammatory disorders. The company has upgraded its forecasts for both drugs, which it now says will earn $21 billion combined in 2027, approximately equalling Humira’s peak sales.

One major reason Humira achieved its massive sales was the many different autoimmune disorders for which it gained approval. With follow-on biologic drugs, however, the incentives to do so may be limited by the Inflation Reduction Act, which gives the federal government the power to negotiate lower prices within Medicare, said Mara Goldstein, Mizuho Securites’ senior biopharma analyst.

“We’re living through this real time and it’s a little challenging,” she said. “Does it truly create a disincentive to develop indications? Will companies continue to invest in new clinical trials right up to patent cliffs? How does [the law] change the value of dollars invested over time?”

New lessons to learn

AbbVie followed the lessons of the previous patent cliff by merging with Allergan in a 2019 deal that gave it enough new revenue to withstand the expected erosion of Humira's sales. Its approach was similar to large pharmaceutical companies’ strategy ahead of the 2010s patent cliff, which spurred the megamergers of Pfizer with Wyeth and Merck with Schering-Plough.

Megamergers might not be the answer this time, however. For one, current pharma executives have expressed reluctance to do big deals because of the complexity of combining two companies. There is debate, too, over the effects such deals have on market valuation and R&D productivity afterwards.

Another reason is that, after years of industry consolidation, there are not many major large drugmakers left as attractive merger targets. Those that remain have patent cliffs of their own, Goldstein said.

Instead, the hunt for new products will either be in big drugmakers’ own laboratories or in those of smaller biotechnology companies. By having two successor blockbusters already in waiting, AbbVie has shown it can execute on the former approach.

Yet, across the industry, big drugmakers’ “R&D productivity is not necessarily corresponding to the R&D investment,” Ural said. R&D productivity and returns have, with a few exceptions, steadily declined each year over the past decade, according to data from both IQVIA and Deloitte.

Meanwhile, in biotech, “there may not be enough assets out there,” Ural added. “It’s going to be a fight for established assets, of which there aren’t that many.”

That fight will be fueled by large cash holdings. Jefferies analyst Michael Yee estimates big drugmakers have $500 billion in cash to spend on acquisitions and other pipeline-building transactions. Small and mid-sized biotechs have simultaneously seen their valuations drop, limiting their financial options, Yee wrote in a Feb. 5 note to clients.

The experimental drugs large pharma companies chase, through acquisition, licensing or inside research, might need to be different, too. They could find advantages in development platforms that can generate multiple new medicines like messenger RNA, gene editing or next-generation antibody technology, or in drugs that have promise across multiple indications.

Humira-sized blockbusters may become harder to achieve, though, which will change how drugmakers develop and commercialize new products, said Bill Coyle, global head of biopharma at consulting firm ZS. AbbVie, for example, needs two drugs — Sykrizi and Rinvoq — to replace sales of Humira.

“I think we’re potentially entering an era of fewer blockbusters and a lot more smaller products,” he said. “The other shift for many of the big pharmas is that their cadence of launch needs to be more efficient and frequent. They need to become more effective launchers of new assets.”

Patent thicket-ing

For drugs further from patent expiration, extending the date of generic or biosimilar entry through the construction of a “patent thicket” is another tactic drugmakers are pursuing. By surrounding Humira with dozens of patents in the U.S., for example, AbbVie pushed off biosimilar entry by seven years after the drug’s principal patent expired.

Others in the industry are seeking to do the same. Merck is testing a subcutaneous version of the intravenous Keytruda, which could potentially merit a separate patent and extend its market exclusivity by years.

A trial of subcutaneous Keytruda in lung cancer is due to deliver results this year. While subcutaneous Keytruda would likely still be delivered by physicians, it could be more convenient. “It’s not the same as having to get an IV, where you have to sit in a chair for an hour or two,” Kelly said.

Other drugmakers sought to push out the entry of biosimilars using this strategy, including Johnson & Johnson with its multiple myeloma medicine Darzalex and Bristol Myers with its Keytruda rival Opdivo.

Already, Bristol Myers has benefited from such intellectual property practices with its medicine Revlimid. The blood cancer drug’s exclusivity was protected by patents held by its original developer, Celgene, that were strong enough to keep most generic competition at bay through 2026. That will give Revlimid, a small molecule drug, a pattern of sales decline that looks more similar to biologic drugs, at least for a few years.

Tahir Amin, founder and executive director of the Initiative for Medicines, Access & Knowledge and a critic of pharma companies’ intellectual property practices, said he expects drugmakers with approaching cliffs to use late-earned patents to delay competition.

Striking limited distribution deals with copycat drugmakers, as Celgene did with Revlimid, could also be a tactic to stave off government drug price negotiation, because the Inflation Reduction Act limits that authority to only those products with no competition.

“At the end of the day the patent system is going to define how they shape the market,” he said.

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By Real Chemistry

Between the bounty of real-world data and a new generation of high-powered analytics tools, life science leaders have more resources than ever to find and engage target customers, be they patients or health care providers (HCPs). And yet many still struggle to find and engage the right people at the right time with the right messaging. What’s going wrong?

Let’s explore some frequent missteps and tips to overcome them.

Tip #1: Machine learning tools can help find patients that even the best data sources might miss  

Most biopharma companies have the data and resources to find patients within narrowly defined parameters, but all too often, they don’t think broadly enough, especially when looking for a particular sub-segment of patients or those diagnosed with a rare disease. This requires asking different and potentially more nuanced questions upfront.

By now, most leaders understand the value of setting up alerts that get triggered by specific events —such as when a patient receives a new diagnosis or initiates a new treatment. But too few use artificial intelligence (AI), machine learning (ML) and other analytics to find potential patients who may be underdiagnosed, misdiagnosed or about to stop an alternative treatment.

In fact, in a survey Real Chemistry did with studioID, just 34% of respondents said they used AI/ML to find undiagnosed or misdiagnosed patients, versus 53% who said they used those technologies to find new patients for products. Technologies such as AI and ML don’t just find potentially “unfound” patients, they establish a predictable order from a chaos of disparate data points.

Even in rare diseases, with all their misdiagnoses and winding journeys, these patterns are still consistent. And not using AI and ML to track them overlooks enormous potential for impact.

Tip #2: Strive to understand HCPs as people, not just prescribers

Most commercially available HCP datasets are static and lack sufficiently robust profile information about how those clinicians make choices and what factors may influence those choices. This limits life science companies’ ability to use their HCP analytics tools in ways that can meaningfully improve activation and engagement. Without understanding who the prescribers are in their “native environments” — such as what they care about, how much clinical decision-making autonomy they have and what their broader patient populations are like — it can be difficult to set up outreach for success.

Although life science companies usually have access to some sort of master provider database, those (sometimes costly) resources can be one-dimensional, lacking contextual richness. For example, many profiles are limited to basics about the practice and the HCP’s demographic background — such as where they went to medical school or from where they’re board-certified.

But does that tell you enough? Not really. By contrast, integrated real-world data, ideally enhanced with AI-derived attributes, can fill in the blanks with details about who providers are as people – how they show up online, how they prefer to consume content, or even whether they consider themselves to be early adopters of clinical innovations. While having those details can inform non-personal promotions such as marketing, they’re also useful for field staff, such as medical science liaisons (MSLs).

Tip #3: Take a data-driven, coordinated approach to omnichannel

Finding potential patients and HCPs is only half the struggle — even if you do everything right
to identify a targetable market segment, you still have to activate them. It’s critical to engage them with the right message, in the right channel, at the right time.

Patient finding, field outreach and HCP digital marketing often get pigeonholed as specific tasks, allocated to specific teams, tied to specific budgets. While that specificity may help an organization’s operations, it jeopardizes program success. Siloed activities tend to result in uncoordinated and misfired engagements that bump up against one another and disrupt the experience for potential customers.

If a manufacturer finds potential patients but then can’t direct appropriate messages so that HCPs are likely to see them, that’s a missed opportunity — not only for the manufacturer but also for the potential patient. The key: look at the data. Companies like Real Chemistry’s Swoop now use advanced analytics to recommend specific messaging, channels and timing. The foundation of those recommendations is relevance.

By using data-driven activation tactics, organizations can get a sense of whether physicians might be motivated by a specific call to action, for example, or whether they’re more open to MSL conversations. You might also see whether they react better to messaging around dosage safety, efficacy or outcomes, and where in the digital universe those messages should go.

Keep in mind, however, that these outreach touch points should still be seamlessly connected with ongoing patient and HCP finding. This helps to avoid blasted, buckshot approaches that engage very few and are disruptive for many — not to mention an expensive waste of resources.

Interested in learning more? Access Real Chemistry’s Customer Finding and Engagement playbook here.

Cigna is moving to limit how much health insurance providers and employers have to pay for pricey and in-demand obesity medications.

The insurer plans to cap annual price increases for the drugs, called GLP-1 receptor agonists, at 15% for employers and plans participating in a weight loss management program offered by its pharmacy benefit manager.

It’s the first financial guarantee available in the market for the drugs, according to the payer. Cigna’s health services division Evernorth, which includes PBM Express Scripts, announced the news in March during the insurer’s investor day in New York City.

The cap could insulate employers from surging costs for GLP-1s while increasing patients’ access to the popular therapies, experts say. GLP-1s have been out of reach for all but a select few, given their high price tags and ongoing shortages of the medications.

The cap is possible through agreements that Express Scripts made with drugmakers Novo Nordisk and Eli Lilly. Cigna is not sharing specifics of the contracts.

As a result, employers and plans participating in Evernorth’s weight management program EncircleRx won’t see more than a 15% annual increase in spending on Novo’s Wegovy and Lilly’s Zepbound, according to Cigna.

In comparison, health plans are seeing the annual cost trend for weight loss drugs hit 40% to 50%, a spokesperson for the insurer said.

“It’s a completely unsustainable number and our clients continue to look to us for help,” Adam Kautzner, president of care management at Evernorth and of Express Scripts, said March 7.

The cap could expand employer coverage of GLP-1s, experts say.

However, a 15% annual price increase being presented as a major step forward on affordability shows both the incredible demand for GLP-1s and the country’s out-of-control spending on drugs, said Arielle Trzcinski, a principal analyst at Forrester.

“It’s a step forward. Is it enough? Maybe not, but in comparison to that 40% to 50% it feels like a much more palatable number,” Trzcinski said.

Cigna’s move illustrates how large insurers are looking for new strategies to prove the value of their pharmacy benefit offerings as they face federal scrutiny into their business practices and competition from drug pricing disruptors.

It’s also a snapshot of the evolving market for GLP-1s, as health services and pharmacy companies look to capitalize on not only providing access to the drugs, but creating services around them.

Increasing GLP-1 coverage

GLP-1s have long been approved to manage diabetes, but the medications — which control blood sugar levels and reduce hunger and food intake — have real potential to move the needle on obesity and the downstream health conditions caused by excess weight, according to physicians and researchers.

Yet payers have been leery about covering the drugs due to their cost. Wegovy and Zepbound — two of three GLP-1 medications currently approved for weight loss in the U.S. — have monthly list prices of $1,349 and $1,060, respectively.

And, the medication needs to be used in perpetuity to maintain its effectiveness. That sustained drain on resources could bankrupt some companies, according to experts.

As a result, only 25% of employers cover GLP-1s for weight management today, according to a recent survey by care delivery company Accolade. More than a third of employers cited cost as a barrier.

Moreover, the drugs remain in limited availability, according to the FDA. The shortages, paired with low coverage rates, are creating a bottleneck for the drugs despite sky-high demand.

More than 40% of Americans are obese, according to government data, creating a total addressable market for GLP-1s of almost 140 million individuals in the U.S.

Cigna’s new program is meant to make future GLP-1 cost trend increases predictable for employers, to give them more financial certainty in covering the medication, Kautzner told investors March 7.

Evernorth is guaranteeing a maximum 15% annual increase in spend. But a company’s specific guarantee differs based on “client type, depending on current benefit offerings and size of patient population, among other factors including specific client preferences and financial strategy,” a Cigna spokesperson told Healthcare Dive.

Cost control risk

Cigna is gambling that it will be able to successfully control medical costs for members of EncircleRx, the weight loss management program Express Scripts launched last summer amid spiking demand for GLP-1s. EncircleRx ties access to GLP-1s with lifestyle modification services like coaching.

Employers pay a monthly fee to enroll their workers in the program. As such, Cigna could generate savings by improving members’ health outcomes and avoiding more expensive medical care down the line.

“If they can improve these individuals’ A1C [levels], blood pressure, cardiovascular health, that has long-term upside for them in terms of savings on medical spend,” said Forrester’s Trzcinski.

Cigna could also be on the hook for excess costs if the drugs and its lifestyle modification program are unsuccessful in changing members’ outcomes.

During the investor day, Kautzner said he was “confident” Evernorth can successfully manage trend, given the division’s history of caring for patients in value-based models. SafeGuardRx, Evernorth’s portfolio of value-based condition management programs, has run risk-based models for hepatitis C, diabetes and other diseases, Kautzner said.

Evernorth has some additional “proprietary” mechanisms that “do limit our downside risk,” Kautzner said.

Cigna has not shared enrollment numbers or savings projections for EncircleRx, but the financial upside of value-based programs can be huge.

SafeGuardRx — which covers 86 million lives across 14 value-based programs, including EncircleRx — created $6.4 billion in savings last year, according to its website.

Cigna isn’t the only insurance conglomerate with a weight management program that includes access to GLP-1s.

UnitedHealth and Elevance launched their own programs in January and February, respectively, for employer clients of their PBMs.

Express Scripts benefit

Expanding access to GLP-1s could also boost revenue for Express Scripts, experts say. That’s because PBMs generally receive larger financial rebates from drugmakers for including more expensive drugs on their formularies.

Starting last year, a number of insurers said rising utilization of GLP-1s was generating notable revenue or earnings in their pharmacy arms. That includes Cigna, which brings in three-quarters of its revenue from Evernorth, and just one-quarter from its legacy insurance business.

“GLP-1 utilization does continue to build, which in the Evernorth business is a positive contributor to our earnings,” Evernorth CEO Eric Palmer said during an August 2023 call with investors.

Enticing more employers to cover GLP-1s “would obviously benefit Express Scripts. They would definitely be incented to do that,” said Jennifer O'Brien, a partner at consultancy West Monroe.

The GLP-1 trend cap could also help Express Scripts in the court of public opinion. Large PBMs have been touting recent cost-cutting and transparency measures as they face rising criticism over their role in increasing drug prices and frustration from employer clients over opaque business practices.

A growing number of employers and plans are turning instead to vendors with clear operational models like Mark Cuban’s Cost Plus Drugs. Still, Cigna’s cost cap shows how major players are jockeying to entrench their position in the GLP-1 distribution market before drug companies fix their supply chains, lessening shortages of the drugs and throwing open the doors to broader access, experts say.

Supply isn’t expected to return to normal until later this year as drugmakers struggle to keep pace with the market’s appetite for GLP-1s.

If insurers and their pharmacy benefit managers already have programs in place to manage that demand, once supply improves they’ll see a windfall, according to O'Brien.

“Once the supply chain is figured out, it’s going to be amazing how many people will be on these drugs,” O’Brien said. “If these PBMs have all these people lined up, waiting — it’s like the amusement park. Let’s open the gates and let everyone in. And they’re well-positioned at that point to receive them.”

Medicare will cover the costs of Novo Nordisk’s obesity drug Wegovy for some patients with a history of heart disease, a policy shift that could significantly open up access to the in-demand weight loss medicine. 

A spokesperson for the Centers for Medicare & Medicaid Services confirmed on late March that obesity drugs receiving Food and Drug Administration approval for an “additional medically accepted indication” may now be covered under so-called Part D plans. Those accepted uses include an approval to reduce the risk of heart problems or treat diabetes, the spokesperson said. 

The new guidance currently only applies to Novo’s Wegovy, use of which the FDA expanded earlier this month based on clinical testing showing it can protect heart health. In a large study, treatment with Wegovy was associated with a 20% reduction in the risk of heart attacks, strokes or cardiovascular death compared to a placebo. 

Those findings separated Wegovy from rival medicines developed by Eli Lilly, which makes Zepbound for obesity and Mounjaro for diabetes, at least for now. Results from a similar trial of Mounjaro are expected later this year. A study of Zepbound could follow a few years later. 

The results were also seen as critical to spurring broader use of Wegovy, as such evidence can convince insurers to cover treatment. Wegoy has a list price of over $1,300 per month and payers have resisted covering the drug.

Medicare is prohibited by law from covering obesity medicines, meaning up until now, people with Part D plans had to cover the drug’s costs out of pocket. The CMS spokesperson said that Part D plans may consider using prior authorization for obesity drugs to “ensure they are being used for a medically accepted indication,” and not only weight loss. Those seeking coverage without a history of heart disease would need their plans to offer a supplemental benefit.

Even with those barriers, Wegovy has gotten off to a fast start. The drug generated about $4.5 billion in sales in 2023 despite manufacturing issues that made it difficult for the company to meet surging demand. Mounjaro, too, has quickly become a blockbuster, making obesity medicines one of the most lucrative opportunities in the history of the pharmaceutical industry. Analysts at investment bank Leerink Partners expect obesity drugs to generate $158 billion in yearly sales by 2032. 

Medicare’s shift in guidance could boost those estimates, broadening access to Wegovy and other weight loss drugs.  

Biogen plans to increase the number of salespeople selling the company’s prized drug for Alzheimer’s disease, now that some of the initial challenges launching it have been worked through.

The drug, branded as Leqembi, generated $19 million in sales between January and March, nearly triple what was recorded over the final three months of last year. Biogen co-developed Leqembi with the Japan-based pharmaceutical firm Eisai, which has led U.S. commercial operations since the therapy gained approval in early 2023.

On an earnings call April 24, Biogen executives said the estimated number of patients on Leqembi more than doubled between the fourth quarter and the first quarter. Order volume also tripled at 100 “integrated delivery networks” that the company has deemed high priority because they treat so many patients.

The growing demand has convinced Eisai and Biogen the time has come to invest more in their sales and marketing efforts, so the latter is expanding its Leqembi field force by 30%.

“Generally, we look at revenue as a surrogate for demand,” Biogen’s CEO Chris Viehbacher said on the call. With Leqembi, however, “that linkage is not quite so clear, because it has taken this upfront time before you see revenue pulled through.”

“In this first quarter ... we're actually seeing a little bit more of that linkage,” he said.

Viehbacher said it's too early to forecast future Leqembi sales. “But I would certainly say I'm extremely encouraged by the progress that has occurred.”

To Biogen, the commercial success of Leqembi is vital. The company’s revenue has been in decline for much of the past four years as courts knocked down key patents protecting its core multiple sclerosis business and new competition began to whittle down one of its top-selling medicines. By Biogen’s estimates, the best path to near-term growth lies with Leqembi and two other new-to-market products that, respectively, treat postpartum depression and a rare disease known as Friedreich’s ataxia.

Even though Biogen and Wall Street had high hopes for Leqembi, getting the drug to patients has proven more arduous and time-consuming than expected. The Centers for Medicare and Medicaid Services, which insures a large segment of the Alzheimer’s population, has policies that, until recently, strictly limited access to Leqembi.

Administering the drug is another challenge, as it requires an hourlong intravenous infusion every two weeks as well as a series of brain scans. Treatment centers offering Leqembi have therefore had to devote significant time, money and manpower to ensure patient access.

Viehbacher said that, at one hospital he and the Biogen team visited, staff claimed it took three months to get approval to hire a nurse who could help them navigate the system. He also recalled how a different medical center had to develop a five-year business plan to be able to access infusion beds.

“I've been in this business for three and a half decades. I've lost count of how many launches I've seen. But this is an extraordinarily difficult launch, because the amount of change that physicians are facing with this is really profound,” Viehbacher said.

According to Alisha Alaimo, president of Biogen’s North American operations, the goal with the expanded field force is to hasten uptake of Leqembi at those large integrated delivery networks.

Alaimo noted how some of those networks are already opening up satellite offices, through which more patients will be diagnosed and treated. She predicts an increase throughout the rest of the year in the number of physicians prescribing Leqembi.

Across the broader business, Biogen recorded total revenue of $2.3 billion in the first quarter, down 7% from the same period a year prior. The company reiterated that total revenue is expected to decline by a low- to mid-single digit percentage compared to 2023, with its core pharmaceutical revenue being about the same.

When Katherine Wisner began studying postpartum mental health in the 1980s, the field barely existed. Relatively little research was focused on psychiatric illness related to pregnancy, and postpartum depression wasn’t yet well understood.

Wisner, now an associate chief of perinatal mental health at Children’s National Hospital in Washington, D.C., recalls a senior male supervisor dismissing a case she flagged of a new mother experiencing severe depression and suicidal thoughts. “You have to be wrong,” she remembers him responding. “Women aren't depressed in pregnancy, because they're fulfilled.”

For years, the idea that having a baby is one of the happiest times in a mother’s life persisted despite research indicating that’s not always the case. Over time, though, researchers and physicians began to acknowledge the range of mental health effects a postpartum woman can experience, spurring research into medicines that might help.

Now, doctors in the U.S. have two drugs they can prescribe specifically for postpartum depression, or PPD, a condition that affects an estimated 1 in 8 women following birth and can be severe. Both are from biotechnology company Sage Therapeutics. An intravenous injection called Zulresso was approved in 2019, while a daily oral pill called Zurzuvae got clearance last summer.

Their approvals were many years in the making. Yet both come with risks and limitations, and adoption has been slow — a fact some experts attribute to still-evolving awareness of PPD, and how to treat it.

“We are not recognizing it as a country and as a society,” Wisner said.

Slow recognition

Mental health professionals have relied on a guidebook called the Diagnostic and Statistical Manual of Mental Disorders, or DSM, to diagnose and treat their patients for more than 70 years.

But the DSM didn’t recognize PPD until the 1990s, when its fourth edition codified the condition as a “major depressive disorder occurring within four weeks of giving birth.”

The next edition, in 2013, went a bit further, defining PPD as a major depressive episode occurring during pregnancy or within four weeks after giving birth. The most recent update also highlights possible coexisting symptoms of anxiety and panic.

“Slowly the field grew so that eventually there actually was a formal diagnosis of depression,” said Wisner.

The drawn-out recognition of PPD left women dealing with the condition to fend for themselves for decades. It wasn’t until 2015, for instance, that the American College of Obstetricians and Gynecologists issued its first guidance on screening for symptoms in both pregnant and postpartum women.

The U.S. Preventative Services Task Force and American Psychological Association soon followed with similar recommendations.

“Historically, the messaging was that pregnancy is the greatest time in a woman's life, and there's no happier time than after a baby’s delivered,” said Julia Riddle, a reproductive psychiatrist and assistant professor at the University of North Carolina School of Medicine. “And it took a lot to really demonstrate that, maybe, it's a little more complicated.”

Difficulties in diagnosis

Even with formal screening recommendations, diagnosis can still be challenging. Questionnaires like the Edinburgh Postnatal Depression Scale and the Patient Health Questionnaire are often used by doctors to determine whether new mothers may be experiencing PPD or anxiety.

If PPD is suspected, psychotherapy, or “talk therapy,” is typically the first option. Drug intervention is usually reserved for more severe cases or for women who were previously on medication.

Actually receiving treatment can be a hurdle, too. Michelle Visser, a mother and psychotherapist for pregnant and postpartum women, recalled how few people asked about her mental health after she gave birth.

“A lot of people don't necessarily know when they need help, because people aren't talking about it,” Visser said. “You don't know what you don't know.”

Partly as a result, PPD is often underdiagnosed and, even when it is, not well treated. According to the Centers for Disease Control and Prevention, approximately 60% of women with symptoms of postpartum depression go undiagnosed, and half of those diagnosed aren’t treated.

“People tend to do the [Edinburgh] scale and then move on,” said Judith Joseph, a psychiatrist at NYU Langone Health and a researcher on trials of Sage’s PPD drugs. “Many times, there's shame in reporting any type of sadness to the provider because if your baby's happy and healthy, you should be happy and healthy too.”

Moreover, not every OB-GYN is trained to treat PPD since it has not always been a part of standard care. Access to therapies can also vary depending on a person’s insurance coverage, resources, or other health concerns.

Treatment shortcomings

Before Sage’s drugs were available, physicians treating PPD typically turned to standard antidepressants like selective serotonin reuptake inhibitors, or SSRIs.

These medicines can help, but their effects don’t usually kick in for four to 10 weeks, if at all. The evidence supporting their use in PPD is also limited.

“When people are having depression, that impacts their functioning and their quality of life,” Joseph said. “Telling them they'll get relief in eight to 10 weeks is very difficult to hear for someone who has a lot of responsibilities, who wants to be able to bond with their child, who wants to be able to get back to the life that they once had.”

Antidepressants can also cause weight gain, gastrointestinal issues, agitation and sleep disturbance.

Doctors need to evaluate prospective patients for bipolar disorder before they prescribe an antidepressant, too. Up to 1 in 5 people screened for PPD may instead have bipolar disorder, a mental illness that causes mood swings and psychosis. Antidepressants can exacerbate bipolar disorder.

Additionally, treatment can be a difficult choice for pregnant or postpartum women, who may feel pressured to go without therapy or fear a drug might affect their child through breastfeeding. (Breastfeeding while on medication doesn’t necessarily present a risk to the infant, however.)

“There is stigma because people assume that motherhood should be inherent to being a woman,” Joseph said. “But [people] don't necessarily acknowledge the challenges.”

Socioeconomic status, ethnicity and familial support can also affect how someone might view receiving help.

“We treat in the medical system, for the most part, people of color totally different,” Visser said. “Those families are very concerned they're going to be seen as unfit parents and that action will be taken against them.”

A sparse drug pipeline

Despite a push for better treatments, the development of drugs specifically for PPD has been sluggish. Research has largely centered on psychotherapy and existing antidepressants.

“We weren't even recognizing these [postpartum] illnesses decades ago, so we weren't going to do trials trying to find a medication specifically for these illnesses,” said Nancy Byatt, a perinatal psychiatrist and professor at UMass Chan Medical School.

Compounding the difficulty is the fact that clinical studies have historically not always included women, nor have drugmakers focused on illnesses that primarily affect women. Clinical trials frequently exclude pregnant women over concerns an experimental drug may harm a fetus and, as a result, researchers don’t know as much about how different types of drugs can affect pregnant women.

Enrolling postpartum women in trials is complicated, too, as the window of time to test a therapy is small.

“It’s still hard because we're talking about nine months. People are often not talking about their pregnancy until three months in,” Riddle said. “So you have a very brief time to consent them, get them onto a protocol and follow them into the postpartum. It's a hard thing to study.”

Sage has been one of the few biotechnology firms to try. The company set out early last decade to develop the drug that became Zulresso, which was approved in 2019 for moderate-to-severe PPD. Its modest efficacy and 60-hour infusion requirement has kept adoption minimal, however.

Working with Biogen, Sage later developed an oral drug called Zurzuvae that it sought to get approved for both PPD and in major depressive disorder. In 2023, the FDA approved it for PPD, but not MDD — a blow to the company that led to layoffs.

Earlier academic research had set the stage for Sage’s drugs. Studies found that depressive symptoms caused by changes in certain brain chemicals during pregnancy might be alleviated with drugs that act on so-called GABA-A receptors. Both of Sage’s PPD drugs are synthetic versions of a neurosteroid called allopregnanolone, a brain hormone that affects GABA-A receptors. They essentially work similarly to hormone therapy, suggesting the role hormones might play in PPD.

“For a long time, it's been debated whether postpartum depression is just another form of major depressive disorder or it's an entity by itself,” said Bassem Maximos, an OB-GYN in League City, Texas and a trial investigator. “A lot of us OB-GYNs believe there has to be a different mechanism because a lot of our patients are different from regular major depressive disorder patients.”

Beyond Sage’s drugs, the pipeline of therapies in development for postpartum depression is thin. Brii Biosciences, another biotechnology company, has a drug in mid-stage testing, but there are few others. 

Will PPD drugs succeed?

While Zulresso and Zurzuvae’s approvals were a milestone for PPD drug research, neither has been widely used.

Zulresso’s lengthy administration must take place in a healthcare facility, keeping adoption low, while Sage faced pushback for the drug’s $34,000-per-course price tag. Sales were $6.7 million in Zulresso’s first full year on the U.S. market, and only $10.5 million last year.

The FDA, as well as psychiatrists like Byatt, agreed Zulresso’s “benefits outweigh the negatives.” But the drug’s requirements make it a hard sell, especially for women who lack additional support, or are a single parent.

Zurzuvae, which launched commercially in the U.S. last December, seems more attractive. As an oral medicine, the drug can be shipped to a patient’s home and is taken daily for two weeks. Psychiatrists, OB-GYNs and primary care physicians have already started prescribing Zurzuvae, with $12 million in sales for the first quarter.

Zurzuvae takes effect rapidly, which could help it stand out compared to other medications, such as SSRIs, that have a slower onset of action. In clinical trials, Sage also found its drug could relieve symptoms of anxiety.

“The fact that this medication works quickly, and also gives [patients] that added relief for sleep and anxiety is beneficial compared to an SSRI that works slower, and may not necessarily relieve sleep and anxiety as rapidly,” Joseph said.

Zurzuvae, which is being co-marketed with Biogen, costs $15,900 at list price for a two-week course — less than Zulresso, but still high enough to raise access concerns.

While Zulresso’s and Zurzuvae’s side effects are modest, both carry black box safety warnings. Zulresso’s warns of excessive sedation and loss of consciousness, while Zuruvae’s cautions of impaired ability to drive. However, Maximos claims the drowsiness was a “positive side effect” for some mothers in the clinical trials who suffered from a lack of sleep and exhaustion.

“It's exciting that we're here,” Riddle said “It's exciting that women have spoken up about their struggles, and that women have taken the time to say, ‘hold on, [motherhood] was actually hard.”

Beyond drug-specific challenges, new mothers face other hurdles that can impact PPD care. Paid maternity leave is not guaranteed in the U.S. and many women are in so-called maternity care deserts, making finding adequate support difficult.

“We always want better treatments that work but the reality is we're not getting the treatments we have to the people who need it right now,” Wisner said. “That's where the big gains are going to come from.”

In an effort to make treatment easier, Sage and Biogen have launched a patient support program, and are working with organizations on PPD education initiatives.

Some experts think a bigger change around culture and access is needed, however.

“The main way that we could possibly address mental health — what's been a crisis for years and is now an emergency — is by supporting resilient and healthy families, and we have to start with perinatal mental health to be able to do that,” Byatt said.

Still, there is some optimism. Joseph sees Sage’s approvals as opening the door to more drug research, for instance.

“This is an opportunity to pave the way for a huge amount of research in this space,” Joseph said. “It's just the beginning.”