Rare diseases

Business was booming for Swiss pharma giant Novartis in the second quarter of 2025 with 11% net sales growth riding strong performance from major drugs. But one of the company’s “priority brands” rests squarely at the bottom of the pack, reflecting broader difficulties in the struggling gene therapy space.

Sales for Zolgensma, Novartis’ rare disease gene therapy for spinal muscular atrophy approved in 2019, fell 17% compared to the same quarter last year, bringing in only $297 million. At launch, Zolgensma was the most expensive treatment in the world, and Novartis expected blockbuster peak sales potential. Now, the company is struggling to find new patients.

Zolgensma got off to a strong start following its May 2019 FDA approval, with net sales of $361 million that year. Then in 2020, its first full year on the market, the gene therapy almost hit the blockbuster threshold with $920 million in net sales, and in 2021, it reached $1.35 billion.

That’s when things got more difficult. While Novartis still saw growth in Zolgensma sales in 2022, the curve began to flatten. The following year marked the therapy’s first annual decline, just four and a half years after launch. What happened?

In Novartis’ first-half earnings report, the company kept Zolgensma talk to a minimum, noting in a release that “sales declined reflecting a lower incidence of SMA compared to prior year, while demand remained robust.” Executives did not address the therapy on a call with analysts.

Gene therapy tribulations

As a gene therapy for a very rare disease that mostly affects children, Zolgensma has had a difficult road on the market. A one-and-done treatment originally listed with a price tag of $2.1 million, Zolgensma targets a disease diagnosed in just 450 to 500 U.S. children each year, Novartis said when it was approved. Now, its initial sales bump has diminished.

Novartis is betting on the potential for approval in older patients to see a rise in Zolgensma’s fortunes, and at the beginning of this year, CEO Vas Narasimhan said annual sales could turn it into a $3 billion-plus earner. The company has conducted clinical trials in older patients, but the landscape for SMA has changed over the course of a decade with competitors crowding the field.

At the beginning of 2023, Narasimhan acknowledged the full-year dip, saying that reaching new geographies would be critical to finding new patients. As of last year, Zolgensma was approved more than 51 countries.

“Growth now is largely dependent on adding additional countries in emerging markets around the world,” Narasimhan said, adding that he expected sales to “stabilize” to $1.5 billion until a potential approval in older patients.

With the current limited indication for Zolgensma, rightsizing the model for sales growth has been difficult. And in the broader gene therapy space, the industry has come to a crossroads that could make those efforts even more challenging to overcome.

In 2022, Novartis confirmed the deaths of two patients who developed acute liver failure associated with Zolgensma. While Narasimhan said at the time that safety was likely not related to slipping sales, the gene therapy world has been rattled by patient deaths that have taken a financial and regulatory toll.

Most recently, Sarepta Therapeutics has dealt with the blowback from the death of a patient treated with the company’s Duchenne muscular dystrophy gene therapy Elevidys. Sarepta’s delayed disclosure of the matter caused the FDA to demand the company withdraw the treatment, but it has so far refused to do so.

The problems associated with safety, price and the limited patient pool for gene therapies have coalesced into a difficult market for companies like Novartis and Sarepta, both of whom have poured billions into development. But that hasn’t stopped them from keeping the dream alive.

Last year, despite the challenges with Zolgensma, Novartis announced the $1.1 billion acquisition of gene therapy platform company Kate Therapeutics, which develops technology that could improve how these treatments work.

Between a 20% reduction in workforce in April and the departure of several top officials across departments, the FDA is undergoing a major transition.

The job cuts have heightened concerns about potential delays and raised questions about how the federal regulator will keep up with its workload. But Commissioner Dr. Marty Makary has vowed to keep the review wheels churning, and the FDA recently launched its AI tool, Elsa, to help. 

So far, the overall rate of drug approvals appears to be on track (or better) for the year. And the FDA is looking at other new initiatives to speed up drug reviews. While some of the proposed programs are still short on details, the FDA is expected to release more information about its plans in the coming months. 

Here’s a look at some of the new programs and tools at the FDA aimed at streamlining reviews.

A voucher-based approach

The FDA recently announced plans to launch a new voucher program, with the lofty goal of reducing drug review times from as long as a year to as little as a month for select candidates. Dubbed the Commissioner’s National Priority Voucher program, the concept replaces the standard review with a team-based approach in which “a multidisciplinary team of physicians and scientists” will review submitted information in one day. 

Makary, a surgical oncologist, said the review process will be similar to how teams of doctors make decisions on “major life-and-death questions for patients” in a “one-day tumor board-style discussion.” The agency also stated it would issue a “limited number of vouchers” in the first year, designated for companies “aligned with U.S. national priorities.” 

The vouchers operate via four criteria, including if a drug or program addresses a health crisis in the U.S., delivers innovative cures, addresses an unmet public need or increases domestic manufacturing. Drugmakers can be granted a voucher for a specific drug candidate that meets the criteria or as an undesignated voucher that can be used at the company’s discretion. Based on the design, drugmakers would use their voucher to submit the chemistry, manufacturing and controls portion of their application for pre-review 60 days before submitting the final application.

“Using a common-sense approach, the national priority review program will allow companies to submit the lion’s share of the drug application before a clinical trial is complete so that we can reduce inefficiencies,” Makary said in the statement.

The FDA already has voucher programs for drug approvals that incentivize new treatments in certain disease areas, including priority review for rare pediatric disease, tropical disease and medical countermeasures. Unlike the CNPV program, these priority review vouchers can be bought and sold by pharma companies, and they’re sometimes worth over $100 million. 

The CNPV program does not have congressional approval, and the FDA hasn’t yet clarified the program’s jurisdiction nor how the agency will implement new regulations, according to legal experts. The CNPV program appears to borrow from established voucher programs, allowing drugmakers to pre-submit some information prior to a final new drug application. New vouchers will begin this year.

Not all research experts believe the idea will benefit patients at a time when the FDA is operating on a shoe-string staff, and some have questioned the potential dangers of a faster timeline and the potential for the process to become politicized.

“[T]he commissioner is forcing the FDA to use its limited resources to rush through reviews of new drugs for unclear reasons,” Dr. Reshma Ramachandran, a member of the board of directors of Doctors for America, said in a statement. “Corners are likely to be cut.” 

There’s also potential for increased litigation as some drugmakers will experience “enormous value of a shortened review period” and there’s little transparency so far as to how companies will be selected, according to legal experts at Hogan Lovells.
 

Conditional approval pathway

Prior to announcing the voucher program, Makary proposed greasing the approval wheels for ultra-rare diseases with a new conditional approval pathway. In his plan, drugs could receive conditional approval based on a “scientifically plausible mechanism” rather than randomized clinical trial data. Makary announced his idea for the pathway during an interview with Megyn Kelly in April, in line with his policy-from-the-podium approach to regulating, and no further details on the program have since been released.

Currently, the FDA grants some drugs accelerated approval on the condition that drugmakers complete confirmatory trials. If these later-stage trials fail, drugs could be pulled from the market.

The agency has other mechanisms to speed reviews as well, including fast track and breakthrough therapy designations. So far, based on the few details about the proposed idea, rare disease leaders aren’t sure another pathway is needed. 

“I would say that the FDA already has sufficient pathways to approve what they need to,” Ultragenyx Pharmaceutical CEO Dr. Emil Kakkis said during a panel at BIO this month in Boston, BioSpace reported. Ultragenyx is a California-based biopharma developing gene therapies for rare and ultra-rare diseases.

However, past FDA officials, including Dr. Janet Woodcock, former acting commissioner, and former director of CBER Dr. Peter Marks, have pushed for a revamp of rare disease regulations. 

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By Advanced Clinical

In drug development, rare disease represents one of the most urgent and complex areas of opportunity. More than 300 million people worldwide are affected by one of over 7,000 rare conditions, most of which lack approved therapies. For people living with a rare disease, their caregivers and their families, every advancement brings hope. For sponsors, the stakes are high, and the path forward is anything but linear.

Today’s rare disease innovators must navigate fragmented participant populations, evolving regulatory expectations, and rising demands around access, equity, and speed. As the space evolves, the strategies, delivery models, and partners that bring these therapies to life do too.

As a life sciences consulting and delivery firm, Advanced Clinical consults to help sponsors align strategy and execution, determining the right approach for each program, whether through a CRO, an FSP, a strategic resourcing model, or a hybrid approach. Our experience spans decades of rare disease support, including study startup, regulatory planning, and talent alignment for global, highly complex trials.

Trend #1: The Acceleration of Orphan Drug Development

Despite recent leadership transitions at the FDA, the Orphan Drug Act and EMA’s orphan designation continue to spur development. Incentives like tax credits, fee waivers, and market exclusivity have contributed to a wave of rare disease activity.

These programs don’t eliminate complexity. Trials often involve small, ultra-rare populations, where each participant carries significant weight in the data. Execution must be flawless.

Advanced Clinical managed a global pediatric rare disease program that achieved approvals in both the U.S. and EU with just 12 participants. Regulatory inspections were rigorous, reinforcing the need for precision, documentation integrity, and proactive risk management from day one

Trend #2: Genetics and Precision Medicine Expand the Horizon

Rare diseases are often monogenic, making them well-suited for genetic and precision therapies. Despite industry-wide financial pressures, breakthroughs in genomics, CRISPR, and biomarker discovery continue to unlock new therapeutic avenues.

But precision requires infrastructure. Natural history studies are critical to establish baselines and inform meaningful endpoints.

Advanced Clinical works with sponsors from the earliest phases to align the right expertise and operational support and infrastructure at each stage of development.

Trend #3: Trial Models Adapt to the Realities of Rare

Rare disease clinical trial participants often face access barriers including mobility limitations, few trial sites, and minimal proximity to specialists. Decentralized and hybrid models offer vital, patient-centric solutions, designed with patient recruitment and retention in mind

Flexibility can increase complexity, which is why an experienced partner is essential for rare disease studies. Designing the right model requires more than technology, it requires clinical insight, logistical coordination, and site input.

Advanced Clinical draws on real-world experience implementing these models across continents. We engage directly with sites to co-develop feasible, patient-centric protocols.

Trend #4: Participant Advocacy Is Reshaping Development

Rare disease communities are highly organized and engaged, often influencing trial design, recruitment, and regulatory conversations.

Agencies continue to prioritize tools like participant-focused drug development (PFDD) meetings and participant-reported outcomes (PROs). Sponsors that delay engagement risk losing trust or missing critical insights.

Advanced Clinical partners with global advocacy groups at the feasibility stage and beyond, integrating community feedback into design and planning. These relationships aren’t performative, they are a core part of how we help sponsors build more inclusive and effective trials.

Trend #5: Data Is Getting Smarter and More Actionable

Traditional trials aren’t always feasible in rare disease. Regulators are increasingly open to real-world evidence (RWE), historical control data, and registries to support approvals.

These data streams require strong systems and governance. For small sample sizes, Advanced Clinical often recommends managing Key Risk Indicators (KRIs) through participant-to-participant comparisons rather than site-level assessments to gain meaningful insights.

From registry design to wearable integration, we help sponsors craft data strategies that are both scientifically valid and operationally sound.

Trend #6: Globalization Is the New Norm

Rare disease trials often require a global reach to identify enough eligible participants. This means navigating varied regulations, cultures, and operational realities.

Success isn’t just about going global, it’s about thinking local, too. Advanced Clinical delivers global reach with regional precision, leveraging trusted site partnerships and staff embedded in-market to manage logistics, approvals, and engagement.

And today, enrollment isn’t enough. Long-term site and patient relationships are essential for retention, follow-up, and ongoing data collection.

Conclusion: Collaboration Is the Catalyst for Rare Breakthroughs

Developing treatments for rare diseases is among the most challenging and meaningful work in life sciences. It demands strategy, unwavering focus on participants, and speed.

Consulting partners like Advanced Clinical help sponsors move from possibility to strategy, and from strategy to implementation. With early alignment on goals, delivery models, and risk mitigation, we help unlock innovation—faster, smarter, and with the participant at the center.

The future is rare, but the breakthroughs are real, closer, and faster than ever.

Federal work policies are not the typical focus of patient advocacy groups. But when the Foundation for Sarcoidosis Research dug into the challenges patients face with staying in clinical trials, the solutions were too obvious to ignore.

It all started when the organization turned to its patient community for insights about the clinical trial journey.

A rare inflammatory disease, sarcoidosis disproportionately impacts Black Americans, who are 12 times more likely to die from the condition than the general population.

“It’s really significant, so that was a catalyst for us … to learn how it’s impacting this community,” said Tricha Shivas, chief of staff and strategy at FSR.

The organization surveyed about 400 patients last year and then met with industry leaders to learn more about representation in clinical trials. Ultimately, the efforts pinpointed several key issues such as doctors not informing patients about trials and the challenge of getting time off from work to participate in research. 

“One clinician told us about a patient enrolled in a study but had to spend three to four hours of her day to be in the trial. So her company told her she’d have to drop out of the study or lose her job,” Shivas recalled. “Then it became about: How do we stop talking about barriers and actually make change?”

The linchpin to one solution was the Family and Medical Leave Act. Because the policy’s language only allowed for time off to receive “treatments” for a medical condition, employees couldn’t leverage it for clinical trials, which often administer placebos. But after lobbying the Department of Labor, FSR got word last year that regulators were on board to switch the language and account for clinical trials.

The win reverberated beyond the sarcoidosis community to all participants in U.S. clinical trials. FSR’s policy score also showcased the role patient groups can play in overcoming obstacles to representation in research.

That role has gotten more important this year. Although pharma has invested heavily in boosting clinical trial diversity in recent years, broad anti-DEI measures by the Trump administration have sent mixed signals over regulators’ ongoing support. 

“Advocacy groups are uniquely positioned to understand and speak for patients,” Shivas said. 

Now, the focus is on building that momentum to drive sarcoidosis R&D while broadening clinical trial access and diversity for pharma as a whole. 

Sarcoidosis and beyond

Like many patient organizations, FSR dedicates much of its resources to bolstering drug development. Although FSR doesn’t lead R&D funding efforts for sarcoidosis, the group tracks progress in pharma’s pipeline and helps funnel patients into studies for new drugs. 

A research agenda published this year by FSR also pointed to top priorities for scientists, including the need to find more biomarkers and diagnostic techniques. Because sarcoidosis can affect multiple systems and organs, the disease often presents with a constellation of symptoms that can flare up and fade over time, making it a “very hard disease to diagnose,” Shivas said.

Advances on those fronts will also set the stage for more drug innovations.

The first-line treatment for sarcoidosis is generally steroids, which come with an array of difficult side effects. The drugs also carry comorbidities for the Black community who are already at a higher risk for illnesses associated with steroid use including heart disease and diabetes.

Now, about a dozen new drugs and assays are being tested in clinical trials, Shivas said, and the pipeline includes several innovative approaches such as JAK inhibitors.   

One potentially impactful readout is expected later this year from aTyr Pharma, which plans to publish phase 3 results for efzofitimod, a first-in-class biologic immunomodulator, in pulmonary sarcoidosis.

Meanwhile, the other pillars of FSR’s current work could have ripple effects beyond the sarcoidosis community.

The organization’s Coalition to Transform Clinical Trial Engagement has strung together dozens of industry stakeholders, including pharma, research and healthcare companies, along with leading bioethicists such as Arthur Caplan, to address research disparities in the Black community.

The coalition is aiming to make policy recommendations that break down barriers such as clinical trial compensation.

It also recently launched Champions for Change, an initiative encouraging corporations to offer paid time off for employees who want to participate in clinical research.

As a mature organization that’s been around for 25 years with a key regulatory win under its belt, Shivas said FSR will continue to keep its eye on large prizes that bolster the entire industry. 

“We see these systemic changes as being a part of our mission now,” Shivas said. “We’re not just calling out problems, but identifying actionable changes.”

Without proper incentives, the economic equation of undertaking R&D to treat a small number of patients simply doesn’t match the years needed to bring new drugs to market.

That puts policy front and center in the rare disease conversation as a means to incentivize difficult development programs for patients who would otherwise fall by the wayside. But the pressure is growing amid increased political uncertainty and a risky financial environment, said Josh Trent, CEO of healthcare consulting company Leavitt Partners and a former White House recruiter, HHS deputy director and congressional counsel.

About 95% of rare diseases do not have treatments approved by the FDA, according to a white paper from the Health Capital Group. Although policies like the 1983 Orphan Drug Act incentivize development, the number of approved treatments has dropped significantly in that time as changes in policy have diminished the scale of those incentives, UCB recently reported.

And while rare disease R&D took a hit from recent efforts to dramatically slim down the federal government, policy remains a critical part of the orphan drug infrastructure, Trent said.

“One of the realities of discovering and developing treatments for Americans with rare disease is that being able to do it successfully depends on a robust ecosystem with multiple factors that present challenges,” said Trent, who contributed to the UCB report. “Some of the challenges are policy-related, some of them market-related, and others are just inherent in understanding the etiology of a particular rare disease and the life cycle of development.”

The goal now is to push for policies that will continue to make rare disease drug development attractive for the industry and other stakeholders.

Diminishing returns

The FDA approved only a few rare disease drugs per year ahead of the Orphan Drug Act, Trent said, but then as a result of the policy, the rate shot up to 252 drugs between 2011 and 2020. Now, in an unstable investing environment, that number has leveled out with 27 drugs approved in 2022, according to UCB.

While there’s bipartisan support for improvements to rare disease drug development incentives, successful policies have a hard time seeing the light of day, Trent said.

“We’ve seen Congress get gummed up on how to ultimately get these across the finish line — it’s less about finding consensus on the policy and more about finding consensus on the process for enacting it,” Trent said. “Business decisions are being made on a daily basis, and businesses and investors take clues from the degree of regulatory uncertainty and act accordingly. That tends to be a bad thing for patients over a longer period.”

In many cases, the difficulty of bringing new incentives to the table is a matter of procedural complications and “the nature of policymaking,” Trent said.

“One of the challenges for policymakers, and I have experienced this myself in Congress, is that life is lived looking forward, but understood looking backward,” Trent said. “The nature of policymaking is trying to be informed by what has worked in the past but recognizing that the future will be different — that’s particularly challenging in innovation, because it can be easy to overindex the issue of the moment.”

As technology platforms and market dynamics shift, policymakers have to look ahead five or 10 years without knowing for certain how the overall landscape could change. But if multiple stakeholders across the rare disease ecosystem are aligned — and there is overwhelming support to do so, Trent said — then patients will ultimately be put first.

“The great thing is there are some clear, concrete, bipartisan opportunities to improve the policy environment,” Trent said.

Policy paths forward

Despite the many challenges, several opportunities exist, and they all carry a good deal of support among stakeholders including pharma companies, payers, lawmakers and patients.

One of the ways to protect rare disease drug development would be to amend exclusions for orphan drugs from Medicare price negotiations under the Inflation Reduction Act, Trent said. 

Currently, the IRA excludes drugs that treat only one orphan condition, “discouraging rare disease research and development from further exploring promising research that could lead to additional treatment options,” according to an email from the Rare Disease Company Coalition.

“This creates a roadblock to rare disease innovation, and in turn, the development of treatments for the more than 95% of rare diseases without approved therapies,” the RDCC wrote, pointing to the Orphan Cures Act introduced by a bipartisan team of lawmakers that would do away with the exclusion. “By expanding the single-orphan exclusion, the Orphan Cures Act would open the door for the research and development of existing products that could help find treatments.”

Another potential policy driver of rare disease drug development is the rare pediatric disease priority review voucher program, which once provided vouchers for companies that bring new rare disease drugs to market. The program lapsed at the end of last year and has been reintroduced in 2025 by U.S. Rep. Michael McCaul (R-Texas) in the Give Kids a Chance Act, but has not yet been passed.

“There’s a lot of unity in the rare disease community about the priority and importance of that, and I think it will get done,” Trent said. “It has proven harder to get done in the current environment, however.”

One more way to incentivize rare disease drug development? Restoring the Orphan Drug Tax Credit to its original 50% after tax reforms in 2017 brought it down to 25%, Trent said, calling it a “concrete opportunity.”

Overall, the burden of rare disease is too great for policymakers to ignore the opportunities that come from lowering the bar for new drugs to enter the market, Trent said.

“From an efficiency perspective, we are already paying for rare disease in the form of direct care, but a lot of it is spending that could be more efficient and optimized,” Trent said. “The efficiency argument is important, and every administration, everyone in Congress, wants to be a good steward of taxpayer dollars — the opportunity we have now is the science, and good policy will result in less irrational utilization and more cost savings.”

Twenty-two years in and Alnylam Pharmaceuticals is still not raking in any profit. But that’s a testament to the company’s R&D focus, because it takes more than one or two successful drugs to make a lasting mark on the biopharma industry.

That biotech pluck keeps Alnylam reliant on its RNAi acumen and a strong R&D engine, but also product launches that stick the landing.

“We're still not profitable, so we have to be very thoughtful about how we optimize and how we justify costs,” said Tolga Tanguler, chief commercial officer and executive vice president at Alnylam.

The company’s latest win came in March with a U.S. approval for its drug Amvuttra to treat ATTR amyloidosis with cardiomyopathy. Leading the commercial launch, Tanguler is aiming for Amvuttra to become a first-line treatment due to the severity of the rare disease and the genetic medicine’s ability to knock the illness down more thoroughly than other treatments.

“In some disease categories, doctors like to wait for the more effective option later. Given that this is fast progressing, doctors want to be able to treat this as quickly as possible,” Tanguler said. “One of the challenges in this disease is, when you lose cardiac function, you don’t get it back — if you wait long enough, it’s too late.”

A smaller approach

For more than two decades, Alnylam has worked to bring the Nobel Prize-winning RNAi technology into the rare disease market as a mid-size biotech with stiff competition. Amvuttra’s main competition in the cardiomyopathy space is Pfizer’s tafamidis franchise, known as the brands Vyndaqel and Vyndamax.

Tanguler’s position is unique — once the head of North America rare disease at Pfizer, that franchise was once under his jurisdiction. He also led commercial efforts for well-known drugs like Viagra and Eliquis. But leading the commercial team at Alnylam is different, Tanguler said, in a way that is much better suited for the rare disease market.

“At Pfizer, we were working as a Big Pharma rare disease model, and I don’t think that really works because while large organizations are good at scaling up and driving large indications, they are not always in tune with a smaller, more captive audience like these rare diseases,” Tanguler said.

Tanguler sees the competition as a positive for Alnylam because of Pfizer’s ability to educate physicians and patients about the disease, which is considered to be widely underdiagnosed.

“Obviously, we don’t have the type of resources that a large company like Pfizer could provide, but I look at our science as building a series of skyscrapers with a strong, single foundation,” Tanguler said. “And as a smaller company, we have the ability to go deep into customer segments where you offer value-based solutions.”

Going bigger

Although Alnylam has focused on rare diseases, the company is striving to add more prevalent diseases like hypertension to the docket, partnering with pharma giant Roche in 2023 to co-develop and co-commercialize the RNAi candidate zilebesiran. And Alnylam also has an Alzheimer’s disease program in the works with Regeneron Pharmaceuticals.

“What this is doing for us is building the muscles that we’ve exercised well in the rare and specialty spaces, and building them into more prevalence,” Tanguler said.

One challenge Alnylam faces is addressing patient access issues for genetic medicines like RNAi. Pricing plays a role in that conversation, but Tanguler said Alnylam is suited for the task.

“If we’re going to price something, we’re going to have to price it with what we call value-based agreements — to pay for performance and base it on clinical outcomes,” Tanguler said.

With four products on the market since 2018, Alnylam pulled in $1.6 billion in 2024, enough to mark sizable growth from the previous year but still eclipsed by a $2.4 billion operating budget.

Tanguler said that points to the company’s devotion to R&D, punching above its weight in tackling the next big challenges in science.

“It’s a privilege — when I joined Alnylam, I said to myself, ‘This is the next big thing,’” Tanguler said. “Here we are, standing alone with amazing science and introducing these medicines in the most innovative way.”

When Michelle Werner’s son Caffrey was diagnosed with Duchenne muscular dystrophy five years ago, she felt adrift. Lost in a fog.

“We felt like we were marooned on an island in the middle of an ocean, completely alone and having to figure out how to fend for ourselves in a very foreign situation,” Werner said.

A child’s rare disease diagnosis is devastating news. And for the Alltrna CEO and ex-Big Pharma exec with almost two decades of drug development experience, her son’s journey with DMD also became a call to action.

DMD patients often become wheelchair bound as the disease progresses and face grim prognoses, even if “survival into the early 30s is becoming more common than before,” according to the Muscular Dystrophy Association.

Although it was little solace at the time, Werner had a toolset most parents do not: a deep knowledge of the drug development process and a leadership position in healthcare.

With that experience, Werner also caught a glimpse of the glaring inadequacies rampant in rare disease R&D. At 10 years old, Caffrey didn’t fit the typical diagnosis age of about 2 to 5, and that, along with other factors, made him ineligible for all available clinical trials — a fact Werner learned immediately as she desperately sought options.

“I thought, holy cow, is it really possible that nothing is going on that my son could be eligible for? I felt like he was overlooked,” said Werner, whose 20 years in drug development were mostly in oncology — a field that boasts scores of clinical trials for patients of all ages. “That's how I felt as somebody who had familiarity. Imagine if you have no familiarity, how isolating and disheartening that could feel. That's what these families go through all the time.”

As she wrestled with Caffrey’s initial diagnosis, Werner came to understand ways the rare disease R&D pipeline can be improved. There’s hope, she says, in one day at a time.

Caffrey’s story

The year was 2020 and the world was grappling with the beginning of the COVID-19 pandemic when Werner’s own world came crashing into stark reality. But long before that time, when Caffrey was a baby, there were already signs.

“We noticed, even at 6 months old, that he was missing some of his gross motor skills, like sitting up independently, rolling over — the general consensus was that he had what’s called hypotonia, low muscle tone, and he would just catch up with his peers,” Werner said.

Physical therapy helped Caffrey become stronger and reach a healthy level of development. But later, when the family was living in Stockholm and Caffrey was about 8 or 9 years old, his motor skills deteriorated again. He showed difficulty climbing stairs. He stood up from the ground in an unusual way called the Gower’s maneuver to accommodate weaker hip muscles.

At a time when specialist appointments were tough to come by due to the pandemic, the family was finally able to speak with a neurologist who “took one look at Caffrey and knew it was muscular dystrophy,” Werner said. A genetic test confirmed the worst.

“The first thing when something like this happens is to think, OK, what’s the standard of care? How do I wrap my head around what’s the best possible option we have right now?” Werner said. “That’s when I realized the standard of care is not very good.”

Daily high doses of corticosteroids come with “a battery of side effects that are really atrocious, and that standard of care hasn’t changed for a couple decades,” Werner said, leading her to explore available studies at ClinicalTrials.gov — to no avail.

“It was so disheartening, and as I dug into it further, his diagnosis cast a spotlight on the inadequacies for rare disease drug discovery and development,” Werner said. “I got this pull to professionally transition my career as well.”

A new path

For Werner, a deeply emotional and personal experience was also a professional epiphany.

“Having worked for 20 years in oncology, I feel like I played a small role in bringing novel medicines to patients in those areas,” said Werner, who has headed up cancer drug launches and strategic directions at Novartis, AstraZeneca and Bristol Myers Squibb. “Now, if I’m going to work for another 20 years, I want to do the exact same thing for rare diseases, because I know what it’s like to be a family that feels completely left behind.”

While sometimes viewed monolithically as a business unit, Werner saw an opportunity to look at rare diseases in a new light.

“We have to find different ways to tackle the problem of 10,000 or so rare genetic diseases than the way we’ve been doing it historically,” Werner said. “Novel treatments like gene therapy, gene editing, mRNA, antisense oligonucleotides — you name it — are all very specific for a certain disease or gene or protein, and we can’t tackle a problem of 10,000 diseases one by one, because it’ll be a long time before we make a dent in that problem.”

Most of all, patients like Caffrey don’t have time to wait.

“I feel this incredible sense of urgency because of my family’s real-life experience to make a much more profound, transformative difference in many diseases at a time,” Werner said.

In 2022, amid Caffrey’s ongoing journey, Werner switched gears from the hallowed halls of Big Pharma to the next-generation efforts of biotech innovation. Through the venture capital group Flagship Pioneering, she stepped into the CEO role at the genetic medicine company Alltrna, where tRNA technology was being used “to simplify the problem of 10,000 different diseases into universal diseases that can be addressed with a single tool,” Werner said.

Today, Alltrna has a pipeline aimed at reversing mutations known as codon diseases in the liver, with one candidate revving up for clinical trials and others in preclinical and discovery phases. What tRNA offers for that bucket of rare diseases is what Werner had been looking for: one technology that serves as the groundwork for treating multiple conditions.

One concept Werner brought to Alltrna is basket trials, which she said is a standard oncology approach that puts patients with the same mutation in a clinical study to treat them with one therapy in a disease-agnostic but mutation-specific indication, she said.

“It’s a great way to address the unmet medical need in R&D and it’s a perspective that hasn’t been done so frequently within the rare disease setting,” Werner said. “Not only do you treat the more common of the rare diseases, which is typically where R&D is focused, but you can also bring in the ultra-rare populations that would probably never get a clinical trial in their own right.”

That strategy stems from having both feet in two different worlds as a mother and as a life sciences leader, Werner said.

Mom hat, CEO hat

Werner came to Alltrna with doubts that the two parts of her life could coexist.

“When I first took this job, part of me wondered, am I going to have to compartmentalize being a mom and being a CEO?” Werner said. “But I realized that I’m the best mom when I’m also wearing my CEO hat, and I’m the best CEO when I’m also wearing my mom hat, because I can understand what needs to be done and why things are so important.”

And with Werner’s experience within the machinery of Big Pharma, she sees the power of a smaller biotech that can take risks in the name of science. In past positions, she has had to make tough choices to cut programs that don’t match a company’s appetite for lofty bets.

“Unfortunately, I’ve seen several programs that have stopped or not advanced because there were other ones that were more valuable to the company,” Werner said. “It feeds an issue of patients continuing to be overlooked and underserved, and that’s somewhere I want to be able to make a difference.”

Werner sees Caffrey’s face in every patient waiting for a better option.

“I know firsthand that every single day matters — every single day,” she said. “So if we get data today and make a decision based on it tomorrow, which is something that big companies don’t necessarily have the luxury of doing, we can take on novel modalities and generate new science that can make that difference.”

Progress is being made in DMD with new treatments like gene therapies and exon-skipping drugs, even in the five years since Caffrey was diagnosed.

Turning 15 this year, Caffrey is navigating high school with his service dog Ticket and, like many teenage boys, enjoys video games and “epic fail” videos online. He’s also a big history buff and he makes his own sour pickles at home. Werner said he’s wise beyond his years, not so much waiting for a better treatment than staying optimistic for when that day comes.

“Duchenne is a terrible disease and a terrible diagnosis to have, but it’s at least a disease that’s getting attention,” Werner said. “I’m very, very grateful that there are several companies, mostly small biotech companies, focusing in this arena. That is a blessing, and it’s a better place for us to be than we were a few years ago.”

Still, Werner tries to leave looking into the future for the biotech side of her brain. As a mom, she sees the world a little differently.

“When my son was first diagnosed, I had to learn a really important lesson, which is don’t think about the future that much,” Werner said. “Live in today’s world, not in the future world — he reminds me of this every day, to live the life, not the diagnosis.”

Upcoming patent losses are looming large for a number of pharma giants, including Amgen. 

The company reported a strong 2024, with revenue increasing 19% from the year before to $33.4 billion and 21 products that achieved record sales for the year. But Amgen is also losing exclusivity for several key products, including its blockbusters Otezla and Enbrel, which together racked up more than $1.6 billion in 2024’s fourth quarter alone.

As it looks ahead, the company, like many across the industry, has refocused its long-term strategy to answer the question: What now?  

For Amgen, the answers lie in a wide range of goals, including acquisitions, developing new products in four therapeutic areas, boosting its biosimilar business and maximizing the impact of its portfolio.

The roadmap ties to “ambitious growth aspirations over the next eight to 10 years,” according to Ian Thompson, Amgen’s senior vice president and general manager of U.S. business operations.

“We're well positioned for sustained growth in the near time and throughout 2030,” Thompson said. “We do have products … losing their exclusivity. But with the breadth of the portfolio that we have, we will continue to grow.”

Here’s a closer look at how Amgen plans to stay on the upswing.

Boosting biosimilars

Amgen is investing more in developing biosimilars than it did a decade ago. 

“We're an innovative scientific company … that's the core of who we are,” Thompson said. “But we've also recognized that one of our differentiating capabilities is manufacturing large proteins, particularly monoclonal antibodies.”

Now, the company is seeing that investment pay off. Amgen said in an earnings call last month that it expects biosimilar sales to reach $4 billion by the end of the decade.

The company has already notched a win on that front this year by launching Wezlana, the biosimilar for Johnson & Johnson's powerhouse inflammatory disease drug, Stelara. It also closed out 2024 with the launch of Pavblu, a biosimilar of Regeneron’s blockbuster retinal disease injection Eylea. 

Later in 2025, Amgen plans to launch Bkemv, a biosimilar to AstraZeneca's complement inhibitor, Soliris, and anticipates a phase 3 data readout in the second half of the year for a biosimilar to Bristol-Myers Squibb’s cancer immunotherapy, Opdivo.

A therapeutic focus

In R&D, Amgen is focusing on four therapeutic areas: oncology; general medicine, which includes cardiovascular, bone health and neurology; inflammation; and rare disease.

“We’ve got four large portfolios, balanced in terms of their growth performance and trajectory,” Thompson said. “All have a range of early products in the growth phase, but also some maturing products as well.”

The company is particularly excited about bispecific T-cell engagers (BiTE) like the blood cancer drug Blincyto, which picked up its third approval last year.

“We recently gained new data which brings it into the consolidation phase of acute lymphoblastic [leukemia], and also pediatric phase as well, so we’re able to treat a lot earlier now for small tumors in that space. That’s driving considerable expansion, treating more patients,” he said.

He also pointed to the potential of Imdelltra, which nabbed FDA approval for small cell lung cancer last year for second-line plus patients.

“We have ongoing studies there to bring it into earlier lines as well,” Thompson said. “It’s having a dramatic impact in a disease that was previously very difficult to treat.”  

Amgen’s moves in the rare disease space have been buoyed by its 2023 acquisition of Horizon Therapeutics, which Thompson said gave the company the opportunity to take their treatments into international markets. For example, the company launched Tepezza in Japan and is filing for regulatory approval in other markets, too.

“We see that path unfolding for other assets like Krystexxa,” he said of the company’s treatment for chronic gout. 

Amgen is also looking to expand the reach of its drug Uplinza, which is currently approved for a rare autoimmune disorder.  

“Uplizna’s very exciting, we’re got a couple of new indications coming through on that,” Thompson said.

In the cardiovascular and inflammatory spaces, Thompson highlighted the company’s optimism for olpasiran, a small interfering RNA drug designed to reduce lipoprotein(a) in late-stage development, and Tezspire, which is approved for severe uncontrolled asthma and has shown phase 2 promise for COPD.  

And like many companies, Amgen is playing its hand in the obesity space. Its GLP-1 candidate, MariTide, which it is developing to go up against competition like Ozempic, reported an average weight loss of up to 20% at week 52 without a weight loss plateau in a phase 2 study.

“Whilst there are two companies in the market today, there appears to be plenty of room for treatment options that are differentiated, whether that’s through a differentiated weight loss profile or a differentiated dosing profile or the ability to treat other disorders,” he said.