It’s not hyperbole to suggest that emerging biopharma companies (EBPs) hold the keys to the success of the entire healthcare ecosystem. According to the IQVIA Institute for Human Data Science, the research and analysis arm of IQVIA, EBPs represent 65% of the total drug development pipeline, which is currently nearly 4,000 drugs, more than double the number in 2016. Additionally, 7% of the pipeline is being developed by EBPs in partnership with larger firms, so 72% of all drugs in the development pipeline have an EBP’s stamp on it.

 EBPs represent 78% of the active pipeline in the small but critical area of cell and gene therapies, which will play a substantial role in driving revenue in the coming years. EBPs are little fish in a very big pond, but they are integral to the pharmaceutical ecosystem.

Quality of innovation from EBPs and large pharma

reached out to Bill McClellan, center of excellence lead for launch at IQVIA, to further understand the EBP role. McClellan leads a team responsible for developing thought leadership to provide innovative approaches for launching a brand. The research focuses on patient acquisition and prescriber adoption and productivity, and the findings have fueled offerings focused on launch strategy, commercialization tactics, and performance monitoring.

By McClellan’s count, there have been 275 branded products launched by EBPs, in the US, in the past 10 years, with 75% of them opting to go it alone and launch the asset themselves. The remainder represent the companies or assets that get purchased or engage in some type of partnership—any time you engage in a partnership, the size of your share shrinks. Is it wise to go it alone? “The question from there really becomes: what’s the quality of the product that’s being developed in terms of innovation for both EBPs and large pharma?” asks McClellan. “We score innovation via different attributes that new products would bring over standard of care such as relative improvements in efficacy, dosing, and tolerability improvements, as well as administration or convenience factors. And the numbers for EBPs and large pharma are almost identical.”

IQVIA data on innovation shows that 43% of all assets developed by EBPs are classified as innovative compared to large pharma’s rate which lands at approximately 45%. So, in terms of innovation, they’re on a virtually even playing field —arriving at the commercialization stage with similarly attractive products.

Are EBPs successful when they commercialize?

Many companies make decisions based on forecasts, including pricing, size of salesforce, and approach to market. And they often gauge success based on forecast achievement, but that’s a bit problematic because most forecasts are wrong, and often overstated. Forty percent of worldwide drug launches between 2009 and 2017 failed to meet their two-year sales forecasts.

McClellan’s IQVIA team defines commercialization success via four factors: the ability to generate revenue; the ability to generate market share; competitive rank, which is similar to market share but gauges the competitive intensity within the market that brands are entering; and, most telling when it comes to commercialization, promotional responsibility—are the companies spending to promote, and is it efficient?

“This is where the variance starts to become apparent,” notes McClellan. “Fifty-seven percent of large pharma’s assets are what we deem as successful. EBP companies, on the other hand are significantly lower—we see that success rate is at 39%. So, there’s a significant gap—why is that? And is it cause or effect?”

Typically, large pharma companies have significantly deeper pockets than EBPs. And when you consider the average promotion of an asset developed by an EBP vs. one developed by large pharma, McClellan revealed that, on average, across the last 10 years, large pharma tends to have double the amount of investment in promotion that EBPs have. And when you compare promotion to average sales, and determine ROI, large pharma historically got $2.5 back for every dollar spent on promotion, while EBPs are getting $1.5 back for every dollar spent.

That’s a rather significant difference; that said, in the past two years, with the pandemic-forced embracement of digital, the gap is beginning to close. The commercialization game has morphed via forced virtualization. It’s not all about the size of the traditional tip-of-the-arrow salesforce anymore—it’s widely known that rep access to healthcare professionals (HCPs) has dropped off dramatically, especially in-person, with doctors preferring a more hybrid approach depending on the therapeutic area. And frequency, or the number of touchpoints with HCPs, has also fallen off a cliff, so it’s important companies provide real, personalized value to the HCPs in the minimal interactions afforded.

Overall, the approach has shifted to a mix of in-person and hybrid, and a great deal more of an omnichannel/digital approach. This go-to-market model likely benefits the leaner EBPs. Biohaven and its migraine medication, Nurtec ODT, is one example. The company was small, lean, and almost entirely virtual even before the pandemic hit. So, while most postponed launches early in 2020 at the onset, they engaged employing a range of whip-smart digital techniques and leaning into a few other key avenues.

What are some of those keys? The attention (and cash) applied to market access, awareness, and the overall go-to-market strategy are three that lead to success or failure as posited by IQVIA’s McClellan.

Market access is critical—it can make or break a newly launched product, and company for that matter. According to Dan Sontupe, industry veteran and associate partner, managing director at The Bloc Value Builders: “If you’re the chief pharmacy officer at an Aetna, Cigna, or Caremark, they aren’t going to take a meeting from a small biopharma unless it’s new, differentiated, and it has a really significant impact on outcomes. Most importantly, it needs to be something that’s going to save them money.”

So, the EBPs that manage this well have a strong clinical and economic proposition for payers and patients, experienced teams to negotiate with healthcare access stakeholders, and display the ability to deliver an affordable product and associated support to the appropriate patients. Simply put, large pharma has a lot more leverage due to stature, experience and success, prior relationships, and a great deal of inherent awareness.

“It’s a little more difficult for EBP companies because not only are they launching a brand, but they’re also often launching a company,” McClellan tells 

. “What we’re seeing is that brands that do well are brands that really establish a strong awareness, pre-launch.”

EBPs can spread awareness by highlighting their scientific platform and building credibility, which is usually accomplished through a strong publication strategy early in the process, conference education, and a medical science liaison (MSL) strategy.

Raghu Reddy, chief administrative officer at the SurgCenter of Western Maryland, LLC, an ambulatory surgical center, stresses the importance of conferences. “If there’s a new drug that’s wonderful and isn’t a ‘me-too’ product, it will draw a lot of attention no matter which method of advertising is employed,” he says. “But I really think what gets the most attention is the presentation on a particular product at a conference, even with the marketing piece removed and presented in an unbiased way.”

There are many options to consider when launching a commercial product for the first time. Do you partner with a large pharma? It instantly provides cash, and, as noted, might increase the probability of success. However, the partnership decreases the share an EBP takes away from the venture. In addition to cash and probability of success, the partnership with large pharma immediately inserts experience in the form of technical expertise and resources, as well as awareness. It opens many doors for an EBP’s product and company to help drive commercialization and mitigate risk. And there’s a much higher chance of a liquidity event such as an M&A or IPO.

Perhaps it’s a good idea to go the partnership route for the first drug launched in a pipeline to serve as a crash course to prepare for subsequent launches. EBPs should pursue these alliances in parallel to their fundraising efforts and understand that these collaborations provide a much-needed risk-reduction measure and a higher probability of a liquidity event.

In the end, a company’s go-to-market strategy must provide a clear road across all channels, with key players well considered and designated, and it must be on point and ready to tackle all challenges the market has to offer. Consider this early when deciding how to approach that first foray into drug development and launch. According to Deloitte, “Most new drugs continue with the revenue trajectory set at launch. About 70% of products that miss expectations at launch continue doing so in subsequent years, and around 80% of products that meet or beat expectations continue to do so afterward.”

 A failure to have a strong launch leads to poor results and ultimately a failure of both product and company. There’s a lot on the line with that first product.

 is a senior editor for Pharmaceutical Executive and can be reached at 

https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/emerging-biopharma-contribution-to-innovation/iqvia-institute-emerging-biopharmas-contribution-to-innovation-forweb.pdf?_=1668541637100

https://www.mckinsey.com/industries/life-sciences/our-insights/ready-for-launch-reshaping-pharmas-strategy-in-the-next-normal

https://www2.deloitte.com/us/en/insights/industry/life-sciences/successful-drug-launch-strategy.html

Articles

Features

Emerging biopharma companies are critical to the vibrancy of the healthcare landscape, but their long road of drug development fails to translate to successful market launch more often than it does for large pharma. What can be done to improve those odds?

Biopharma’s Untapped Value: The Quest to Reverse First-Launch Failure Trends

In drug development, innovation happens in two ways: Incrementally, with each iteration of a product marked by slight improvements over what came before it, or exponentially, with new drugs boasting efficacy or safety profiles that are orders of magnitude better than existing therapies. Both approaches hold value. Perfecting established drugs, or finding new ways to apply the principles that underlie them, is equally as innovative as developing new treatments. Moreover, both approaches are imperative to meet gaps in the market and serve patients’ short-term and long-term healthcare needs.

The emerging drugs in the development pipeline have achieved a mix of both, building on therapies that have already been established while also uncovering innovative new approaches that offer unique benefits. 

’s 18th Annual Pipeline Report profiles the best and most noteworthy of these medications, as supported by data from Clarivate Analytics.*

Spinal muscular atrophy (SMA) is a complex condition with a poor prognosis. While some forms of SMA still permit patients to have a typical lifespan with the proper medical care, other forms are often fatal within two years.

 Currently there exists no cure; however, emerging new drugs are showing promise in helping to manage this disease.

William Orent, PhD, life science expert at DeciBio in Los Angeles, says there’s currently a discussion underway around how to change the disease course of SMA in a meaningful way. While gene therapies already exist, Orent says potential newer solutions aim not to manage the disease, but to cure it.

“SMA is the perfect example of diseases being targeted by gene therapy right now,” notes Orent. “It has a clear etiology, and if we can make a genetic edit early enough, we can make an impact. There’s an approved treatment called Zolgensma, and it’s making a dramatic change for patients who receive it early. We should expect to see more going on in gene therapies.”

Zolgensma (onasemnogene abeparvovec-xioi) is a gene therapy sold by Novartis that is administered as a single, one-time intravenous infusion of vector genomes. It’s delivered through an adeno-associated virus vector after a 30-day course of systemic corticosteroids. FDA approved Zolgensma in 2019 for treatment of SMA in patients under age 2 with SMN1 mutations.

In May 2021, Novartis published the results of a five-year extension of its Phase I START trial on Zolgensma. This long-term follow-up safety study monitored 13 patients with SMA type 1 who had been treated with Zolgensma during START; SMA type 1 is typically fatal and usually kills infants before age 2.

 In the trial, however, 10 patients who had received a therapeutic dose were still alive five years after treatment. They were also breathing independently and had maintained their previous motor activity improvements five years after treatment.

While Zolgensma is showing strong results in trials and has FDA approval, it remains prohibitively expensive. In December 2021, the

 Journal of Market Access & Health Policy

 awarded Zolgensma the unenviable distinction of being “the world’s most expensive drug.”

 A single dose of the infusion costs $2.1 million; the drug’s price tag is a result of the expensive manufacturing process involved in creating gene therapy products.

Orent says that gene therapies are very expensive, which is why ROI becomes a challenge, especially in countries with single-payer healthcare systems. However, Orent believes, Zolgensma is such a clear value-add that most countries do end up covering something like it. Still, the pursuit for other SMA drugs will continue unless Zolgensma comes down in price.

Another SMA drug in development, intrathecal OAV101, is also a gene therapy; it is a Novartis drug as well and is showing promise in clinical studies. The STEER trial on intrathecal OAV101 had been previously put on hold; in August 2021, FDA lifted the hold after seeing favorable data from a toxicology study.

 Novartis is currently running STEER, a Phase III randomized, double-blind, placebo-controlled trial. The study is notable in that its subjects are older than most SMA patients; the trial aims to improve motor function in type 2 SMA patients between ages 2 and 18. The STEER trial will involve over 100 subjects and will assess motor function using the Hammersmith functional motor scale (HFMS), Expanded. STEER builds on the previous STRONG trial, a Phase I/II study that showed significant increases in HFMS scores in patients.

An additional Phase IIIb clinical trial, known as STRENGTH, will assess the safety, tolerability, and efficacy of intrathecal OAV101 in subjects aged 2 to 12 years with SMA who had previously been treated with nusinersen or risdiplam. This trial is slated to end in October 2024.

Two other drugs in development for SMA include nusinersen and taldefgrobep alfa.

While nusinersen was FDA-approved in 2016 and was the first SMA drug to hit the market, ongoing research has revealed new insights that could improve its efficacy. Secondary analysis of data from the CS3A and ENDEAR studies found that higher concentrations of nusinersen in cerebrospinal fluid were associated with a greater decrease in pNF-H concentrations as well as higher drug efficacy.

 Nusinersen is currently undergoing a Phase II/III trial, the DEVOTE study, to further examine the dose-response relationship and to assess the safety, efficacy, and pharmacokinetics of higher doses.

 This study of 145 subjects will assess the effects of nusinersen in loading doses of up to 50mg and maintenance doses of up to 28mg/day.

Meanwhile, Biohaven is currently running a Phase III clinical trial on the biologic taldefgrobep alfa, a modified adnectin that acts as a myostatin inhibitor. Known as the RESILIENT trial, it is examining the effects of taldefgrobep alfa in 180 patients who are already on risdiplam or nusinersen, or who have been previously treated with Zolgensma.

 The trial started in July 2022 and is slated to end in January 2025. It will examine the effects of a 35mg or 50mg weekly subcutaneous injection of taldefgrobep alfa, compared to a matching placebo, in subjects with SMA between the ages of 4 and 21. Participants will be assessed for motor functioning via the 32-item motor function measure over the course of 48 weeks.

These trials are just some of the many currently underway for the treatment of SMA. Clarivate Analytics data shows that 138 clinical trials are currently underway for SMA treatments, while another 1,408 are examining drugs for other motor neuron diseases like amyotrophic lateral sclerosis (ALS). Over 200 of these trials are in Phase II, and 474 started within the last seven years.

Intranasal and inhaled vaccines gain renewed interest

The COVID-19 pandemic has resulted in a significant resurgence in new vaccine development, with Clarivate Analytics data showing 2,625 trials for COVID vaccines alone. Over 2,000 trials for SARS-CoV-2, SARS, Middle East respiratory syndrome (MERS), and flu vaccines are recruiting, planned, or otherwise in progress. These trials are almost evenly divided between Phase I though IV. While the general vaccine market has relied on existing therapies for several years, new technological breakthroughs like mRNA development platforms and lipid nanoparticle delivery systems have fuelled a flurry of innovation in vaccines for COVID, croup, influenza, respiratory syncytial virus (RSV), and other infectious diseases. Several of the recent innovations in vaccine development have leveraged aspects of the immune system that came into sharp focus during the coronavirus pandemic.

Orent says there is growing interest in applying learnings from mucosal immunology to next-generation vaccines.

“The idea on everyone’s mind is how to boost immune activity at the site of infection,” he explains. “That’s why the market is looking at mucosal immunity.”

Joe Daccache, PhD, senior life science expert at DeciBio, says the primary activity in intranasal vaccines is around COVID. While RSV vaccines are starting to pick up, researchers are increasingly looking for next-generation COVID vaccines that can perform better than the current vaccines at reducing transmission.

“There are intranasal mRNA vaccines in development, but they’re having trouble with the mRNA degradation,” notes Daccache. “Intranasal flu vaccines are getting some efficacy, but not to the same level as intramuscular. But intranasal vaccine development has picked up a bit.”

Other COVID studies are taking a non-vaccine approach to prophylaxis. One Phase II/III trial currently underway, PROTECT-V, is designed to examine the efficacy of multiple prophylactic agents in preventing COVID infection among high-risk patient populations. The study authors note that a need for COVID prophylactics exists among immunocompromised patients who do not mount an adequate immune response after vaccination. The PROTECT-V trial, sponsored by the Cambridge University Hospital NHS Foundation Trust, will examine the efficacy of niclosamide, ciclesonide, and sotrovimab as COVID prophylactics in 1,500 patients with renal disease. The George Institute is sponsoring a parallel study involving 750 patients in India. The study, which will eventually enroll 5,000 patients, began in February 2022 and is estimated to end in October 2024.

Meanwhile, development of intranasal COVID vaccines has expanded beyond mRNA. One October Phase 1 trial funded by AstraZeneca assessed the tolerability and immunogenicity of an intranasal version of the ChAdOx1 adenovirus vector COVID vaccine produced by AstraZeneca and Oxford University. In this study, 30 unvaccinated subjects received an inhaled dose of varying concentrations of viral particles. An additional 12 unvaccinated subjects received mRNA COVID vaccinations. Six subjects who had received the original ChAdOx1 intramuscular COVID vaccine and six subjects who had received two intramuscular doses of Pfizer’s Comirnaty also received a dose of viral particles. Subjects were monitored for adverse events and for mucosal antibody response.

This trial found that both vaccines were well tolerated. While the participants’ systemic immune responses were weaker relative to intramuscular immunization, the intranasal vaccine did induce mucosal antibody production in a minority of the subjects. The study authors hypothesize that the poor efficacy could be due to the vaccine using a suboptimal viral vector; a more infectious virus that better targets the respiratory system may serve as a better vector for an intranasal vaccine. The authors note that adding mucosal adjuvants may also elicit a stronger immune response.

 While the trial did not produce favorable results, the fact that the vaccine induced an immune response—albeit a weak one and only in some participants—serves as proof of concept that an intranasal COVID vaccine is possible. Still, there is much work to be done to make such a vaccine mass-market viable.

Another notable vaccine candidate aims to prevent croup in children. Currently, no vaccine for the condition exists

; this new candidate would be the first croup prophylactic to hit the market. An open-label, single-group Phase 1 clinical trial sponsored by St. Jude Children’s Research Hospital in Seattle will assess the safety of a live intranasal vaccine in 54 children aged 12 months to 6 years. The trial will use a live intranasal vaccine based on the Enders strain of the Sendai virus to induce immunity; researchers will monitor the children for six months and assess for rates of serious illness and production of antibodies.

While this is a relatively novel approach in humans, this viral vector vaccine has produced favorable results in animal studies; the animals in question developed protection against croup without developing illness. The study authors note that previous pilot trials in humans have found the vaccine to have no serious side effects.

Gene-targeted therapy expands within and outside oncology

Oncology has been driving cell and gene therapy (CGT) development, with some of the early breakthroughs in precision medicine indicated for breast and cervical cancer. Now, however, major advances in precision medicine have given drug companies a reason to look at CGTs for other indications. Orent notes that emerging work in the RNA space has enabled more specific gene targeting, with new approaches involving sRNA and oligotherapies expanding therapeutic options.

“We’ve taken major steps in our understanding of what it means to do gene targeting,” says Orent. “We’ve moved on from early attempts like Herceptin, and have created therapies that can go after these variants across modalities. The top indications for precision therapies aren’t in oncology—they’re things like muscular dystrophy and hemophilia.”

Mike Ward, global head of life sciences and healthcare thought leadership at Clarivate, points out that gene-targeted therapies have seen a significant uptick in recent years. While in years past, 15% of newly FDA-approved drugs were precision, or personalized, medicines, that number now sits somewhere between 30% and 40%, notes Ward. Most of the drugs in late-stage clinical trials are associated with oncology or rare diseases, where gene-targeted therapies rule.

“We’re also seeing the emergence of gene-targeted therapies in other therapeutic areas,” he says. “We’re on the cusp of precision psychiatry, which 10 years ago would’ve been a pipe dream. The revolution going on in psychiatry in the coming decade could look a lot like the advances we’ve seen in oncology in the last 10 years.”

Clarivate data shows that from 2000 to 2009, there were 6,198 clinical trials involving gene therapies, mostly for cancer conditions. From 2010 to present, the top three conditions examined in gene therapy clinical trials were multiple myeloma with 185 trials, diffuse large B-cell lymphoma with 184 studies, and metastasis with 181.

However, gene therapies are also taking aim at the coronavirus and other non-cancer conditions. The No. 4 such condition gene therapy trials targeted was COVID, with 180 trials. Other studies are currently underway for conditions such as refractory angina and hemophilia.

One Phase III clinical trial currently underway is examining the efficacy of tisotumab vedotin, an antibody-drug conjugate that combines the monoclonal antibody tisotumab and the cell division inhibitor monomethyl auristatin E, for the treatment of cervical cancer. This open-label study is assessing the effects of tisotumab vedotin compared to the investigator’s choice of one of five chemotherapy drugs (topotecan, vinorelbine, gemcitabine, irinotecan, and pemetrexed) in 482 women with recurrent or metastatic cervical cancer. The study is expected to have preliminary results in 2024 and be completed in 2028.

 Tisotumab vedotin gained FDA approval in September 2021 following an open-label multicenter single-arm trial and is sold under the brand name Tivdak.­

 The open-label trial, a Phase II single-arm study involving 102 subjects, found that the drug showed clinically meaningful anti-cancer activity in 24% of subjects. While the drug caused one subject to die of septic shock, the study authors say the relatively poor prognosis for metastatic cervical cancer and a dearth of new drugs for this disease area warrants continuation of the drug’s development.

Another gene therapy currently in Phase III trials aims to use a DNA approach to treat hemophilia B. The investigational drug etranacogene dezaparvovec (AMT-061), is a viral vector drug that uses an AAV5 virus to deliver the Padua variant of factor IX. The drug, developed by uniQure, recently completed the Phase III HOPE-B trial, which showed favorable results. The 78-week non-randomized sequential-assignment trial, sponsored by CSL Behring, examined the effects of AMT-061 on annualized bleeding in 54 patients with hemophilia B. In October, the trial reported preliminary results; the investigational drug maintained stable factor IX expression for a minimum of 12 months while also reducing annualized bleeding.

Perhaps one of the most unexpected areas where gene therapies are emerging is in cardiovascular medicine. Past research reviews have found that the gene therapy alferminogene tadenovec could improve exercise capacity; however, this candidate has struggled in clinical trials. Two Phase IIb/Phase III studies in the early 2000s were terminated prematurely due to an unexpectedly strong placebo effect.

Now, however, researchers have returned to gene therapy as a potential treatment for angina. A Phase III trial sponsored by Angionetics will start recruiting patients in January.

 This parallel-assignment trial will assess the effects of Ad5FGF-4, an adenovirus serotype 5 virus expressing the gene for human fibroblast growth factor-4, on subjects with angina. The trial will measure frequency of angina attacks, exercise duration, frequency of nitroglycerin usage, and quality of life in 160 participants, with exercise tolerance test duration as the primary endpoint.

Hemophilia medications undergo intense discovery

There exists considerable research activity in hemophilia A drugs; Daccache says this disease area accounts for most of the activity in gene therapies. This is a significant shift for drug manufacturers, with conventional therapies falling by the wayside.

Most recently, BioMarin’s Roctavian (valoctocogene roxaparvovec) was approved by the European Commission in August. Roctavian first underwent an open-label Phase I/II safety trial starting in December 2020. The trial, which is still recruiting patients, will continue collecting safety, tolerability, and efficacy data until February 2029.

 A concurrent Phase III study involving 22 participants is currently underway, with initial data expected in January. This trial, examining the safety and efficacy of Roctavian in hemophilia A patients who are taking prophylactic corticosteroids, will run until January 2027.

According to Ward, Roctavian is designed to reduce the number of bleeding events in hemophiliacs, which can rid patients of the need for burdensome prophylactic treatments. The drug is designed to reduce the need for replacement factor VIII. “Clarivate analysts are forecasting that Roctavian could reach annual sales of $500 million per year by 2031,” says Ward. “We’ve identified Roctavian as a drug to watch. It’s up for FDA discussion in early 2023.”

While Roctavian is showing strong signs of commercial potential, other contenders are also demonstrating favorable results. Daccache says competition in hemophilia A treatments is intense; DeciBio data shows four clinical trials involving gene therapies and one trial of a nucleic acid therapy in progress. “This is going to be most of the activity in gene therapies,” contends Daccache. “A lot of things are in the discovery stage and are quite promising.”

Clarivate data shows 911 total hemophilia drug trials underway; 641 of them are for patients with type A hemophilia. A large majority of these trials were launched after 2015, and a number of them are currently in Phase III.

While Roctavian is promising, pharma manufacturers continue to investigate other therapies. Larger companies such as Sanofi and Roche, as well as smaller biotechs like Spark Therapeutics, are investing in hemophilia research.

Sanofi’s investigational drug efanesoctocog alfa, previously designated BIVV001, is a factor VIII replacement therapy formulated as a once-a-week dose. In February 2021, efanesoctocog alfa was granted FDA fast-track designation following its declaration of orphan-drug status in 2017.

 The treatment uses von Willebrand factor and XTEN-branded polypeptides to extend its activity and increase half-life.

Efanesoctocog alfa is currently being studied in a long-term safety and efficacy trial, called XTEND-ed, in patients who had previously been treated for hemophilia A. The Phase III open-label trial involving 262 participants aims to assess the effects of efanesoctocog alfa on factor VIII neutralizing antibodies. Secondary outcome measures include number and type of bleeding episodes, physician’s global assessment of response prior to treatment, and change from baseline Hemophilia Joint Health Score. The trial is currently recruiting patients and is estimated to end in 2027.

An investigational drug by Spark, SPK-8011, hopes to affect factor VIII expression in a different manner. It is a gene therapy that uses a bioengineered adeno-associated viral vector to deliver a human factor VIII gene using a liver-specific promoter. In November 2021, Spark announced the results of a Phase I/II clinical trial involving 18 participants. After 33 months, 16 of the 18 subjects had sustained FVIII production and experienced a reduction in bleeding episodes.

 The study found a 91.5% reduction in annualized bleeding, from an average of 8.5 bleeding events per year before treatment to 0.3 events per year after treatment.

RNA therapeutics are also undergoing intense development, with both mRNA, which produces certain compounds, and antisense RNA, which inhibits the production of compounds. There are currently multiple Phase II and III trials underway, as well as hundreds of preclinical studies.

“We’re also seeing expansion across applications,” notes Orent. “It started out with a COVID vaccine strategy, but Moderna has been building their oncology team, and they’re also looking at autoimmune disorder vaccines. The indications mRNA can be used for are increasing.”

Daccache notes that M&A activity in the RNA space has remained strong, and companies are starting to move away from untargeted mRNA to more directed, cell-specific therapies. Targeted nucleic acid vaccines and therapies are showing promise not only for infectious diseases, but also neurology and other areas.

Moderna is currently running a Phase III trial on its mRNA-1647 candidate, a vaccine for cytomegalovirus (CMV). While CMV infections are generally quite mild, a pregnant woman who contracts the virus can transmit it to her fetus;

CMV infection can cause permanent disability or death in the child.

 This trial is recruiting subjects and intends to follow 6,900 women for 2.5 years.

Another Moderna vaccine candidate, mRNA-1345, currently in development is targeting RSV. It’s undergoing a Phase II/III trial on adults over the age of 60. The study is still recruiting participants, and aims to eventually enroll 34,000 seniors. It’s being conducted in two stages, with 400 to 2,000 subjects participating in the Phase II segment. Following that, roughly 32,000 subjects will participate in the Phase III segment. All subjects will be randomly assigned to receive either a placebo or one dose of the mRNA-1345 vaccine. Subjects will be assessed for number and severity of adverse reactions and vaccine efficacy at preventing infection and hospitalization and at inducing the production of neutralizing antibodies.

While mRNA has received much press since the original COVID vaccines were developed, other producers are looking at options involving self-amplifying RNA or combined RNA/mRNA vaccines. Arcturus Therapeutics currently has RNA/mRNA vaccines in development for COVID and influenza, as well as RNA/mRNA therapeutics targeting ornithine transcarbamylase deficiency and cystic fibrosis.

Arcturus’ ARCT-154 COVID vaccine is the most developed of these product candidates. ARCT-154, also known as LUNAR-COV19, is a self-replicating RNA/mRNA vaccine that uses an RNA delivery mechanism to insert spike protein-encoding mRNA into cells. Arcturus claims that an mRNA vaccine delivered using self-replicating RNA can enable smaller doses, as little as 5 micrograms, which would accelerate rollout and reduce manufacturing costs.

 The current trial underway on ARCT-154 is a combination Phase I/II/III study sponsored by Vinbiocare. It will be performed in four parts that will assess the safety, immunogenicity, and efficacy of the vaccine. The final phase will pit ARCT-154 against AstraZeneca’s ChAdOx1 COVID vaccine to determine whether ARCT-154 presents a non-inferior safety and efficacy profile. The trial will eventually enroll 19,400 participants and is expected to be complete in August 2023.

While much ado has been made about mRNA vaccines, emerging drugs in development are also pursuing mRNA as a delivery mechanism for therapeutics. Clarivate’s data shows that more than 190 mRNA candidates are in preclinical development, with 135 drugs or vaccines in various stages of clinical trials. While the largest proportion of these products are designed to treat or prevent infection, there are also mRNA vaccines and therapeutics in development for cancer and metabolic, respiratory, and psychiatric conditions.

Ward says the enthusiasm for mRNA and RNA was spurred by the pandemic. COVID vaccines served as proof of concept for mRNA, he notes, which, in turn, has fueled the rise in development of next-generation RNA and mRNA technology, including self-amplifying RNA. “There’s a lot of RNA technologies that companies are trying to get access to,” says Ward. “We’ve seen a big increase in the number of deals associated with RNA platforms. We’ve even seen some RNA drugs get approved, and more are coming down the line.”

Ward believes the RNA market is particularly exciting given that Moderna and BioNTech (Pfizer’s Germany-based partner on Comirnaty) originally developed their COVID mRNA vaccines for oncology purposes. The pandemic forced both companies to pivot, and that pivot was successful. Now, the major players in RNA and mRNA have the funds to research other disease areas.

“Pfizer and Moderna are refocusing their efforts back on the development of mRNA vaccines for oncology, which is one of the things we’ll be interested to see,” says Ward. “The amount of money both companies were able to make from the COVID vaccines means they’ll be able to really accelerate the scale-up of their activities in the oncology space.”

The therapeutics and vaccines currently in development are testing the boundaries of their fields. SMA drugs such as Zolgensma are delivering life-changing results to trial subjects, while new intranasal and inhaled vaccines have provided proof-of-concept around mucosal immunity. Gene-targeted therapies and precision medicines are expanding into unexpected areas such as psychiatry, while new hemophilia A medications show great efficacy improvements over their predecessors. Permeating the entire field of modern drug development is the RNA and mRNA development platform that the COVID pandemic brought about.

The biopharma pipeline is full of innovative and promising vaccines and therapeutics, with a good number of Phase III candidates nearing potential market readiness. The number and scale of advances in the pipeline mean drugmakers will find ample opportunities for commercialization in these five therapeutic areas and modalities outlined.

*The data provided in the charts on the following pages does not purport to represent complete datasets. All data is based on specific remit and search criteria. Data provider Clarivate Analytics and Pharmaceutical Executive do not make any warranties or representations regarding the completeness of the data presented.

 is a freelance writer based in British Columbia, Canada. His work has appeared in Nutritional Outlook, Hoist, and Massage Therapy Canada, among other publications.

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Mendell JR et al. “Five-year extension results of the Phase 1 START trial of onasemnogene abeparvovec in spinal muscular atrophy.” 

Nuijten M. “Pricing Zolgensma – the world’s most expensive drug.” 

Cumbers J. “Why some drugs cost $2.1 million per dose and how one company plans to change this.” 

“Novartis announces lift of partial clinical trial hold and plans to initiate a new, pivotal Phase 3 study of intrathecal OAV-101 in older patients with SMA.” Novartis. Published online Aug. 3, 2021.

“STEER trial results.” Spinal Muscular Atrophy UK. Updated Feb. 22, 2022.

ClinicalTrials.gov. “Phase IIIb, open-label, multi-center study to evaluate safety, tolerability and efficacy of OAV101 administered intrathecally to participants with SMA who discontinued treatment with Nusinersen or Risdiplam (STRENGTH).” ClinicalTrials.gov Identifier: NCT05386680.

Finkel RS et al. “Scientific rationale for a higher dose of nusinersen.” 

Annals of Clinical and Translational Neurology

, vol. 9 no. 6 (June 2022): 819-829. Published online ahead of print May 13, 2022.

ClinicalTrials.gov. “Study of Nusinersen (BIIB058) in participants with spinal muscular atrophy (DEVOTE).” ClinicalTrials.gov Identifier: NCT04089566.

Biohaven Pharmaceuticals. “Biohaven enrolls first patient in phase 3 trial of taldefgrobep alfa in spinal muscular atrophy (SMA).” Published online July 7, 2022.

ClinicalTrials.gov. “A study to evaluate the efficacy and safety of taldefgrobep alfa in participants with spinal muscular atrophy (RESILIENT).” ClinicalTrials.gov Identifier: NCT05337533.

ClinicalTrials.gov. “Prophylaxis for patients at risk of COVID-19 infection –V (PROTECT-V).” ClinicalTrials.gov Identifier: NCT04870333.

Madhavan M et al. “Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomized ascending dose phase 1 trial.” 

 (Oct. 2022): 104298. Published online ahead of print Oct.10, 2022

Woods CR. “Patient education: Croup in infants and children (Beyond the Basics).” UpToDate. Reviewed October 2022.

ClinicalTrials.gov. “A study to assess the safety of live intranasal Sendai virus vaccine in children and toddlers.” ClinicalTrials.gov Identifier: NCT00186927.

ClinicalTrials.gov. “Tisotumab vedotin vs chemotherapy in recurrent or metastatic cervical cancer (innovaTV 301).” ClinicalTrials.gov Identifier: NCT04697628.

FDA. “FDA grants accelerated approval to tisotumab vedotin-tftv for recurrent or metastatic cervical cancer.” Published online Sept. 21, 2021.

Coleman RL et al. “Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023.ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study.” The Lancet Oncology, vol. 22 no. 5 (609-619): May 2021. Published online ahead of print April 9, 2021.

ClinicalTrials.gov. “HOPE-B: Trial of AMT-061 in severe or moderately severe hemophilia B patients.” ClinicalTrials.gov Identifier: NCT03569891.

UniQure. “Hemophilia B: A potential first- and best-in-class hemophilia B gene therapy program.”

Flynn A et al. “Alferminogene tadenovec, an angiogenic FGF4 gene therapy for coronary artery disease.” 

ClinicalTrials.gov. “Ad5FGF-4 in patients with refractory angina due to myocardial ischemia (AFFIRM).” ClinicalTrials.gov Identifier: NCT02928094.

ClinicalTrials.gov. “Safety, tolerability, and efficacy of valoctocogene roxaparvovec in hemophilia A with active or prior inhibitors.” ClinicalTrials.gov Identifier: NCT04684940.

ClinicalTrials.gov. “Study to evaluate the efficacy and safety of valoctogene roxaparvovec, with prophylactic steroids in hemophilia A (GENEr8-3).” ClinicalTrials.gov Identifier: NCT04323098.

Sanofi. “Efanesoctocog alfa granted FDA Fast Track Designation for treatment of hemophilia A.” Published online Feb. 18, 2021.

ClinicalTrials.gov. “Long-term safety and efficacy of efanesoctocog alfa (BIVV001) in previously treated patients with hemophilia A (XTEND-ed).” ClinicalTrials.gov Identifier: NCT04644575.

Our annual report spotlighting notable investments in new drug development captures a mix of gradual gains and giant leaps—both equally as promising—in five expanding and diverse therapeutic areas: spinal muscular atrophy, hemophilia A, intranasal and inhaled vaccines, gene-targeted therapy, and RNA therapeutics.

2023 Pipeline Report: Testing the Limits

As the US head of rare diseases for UCB in the US, Kimberly Moran has been working in the pharmaceutical industry for nearly two decades and has been a part of UCB for 15 years. During that time, she’s risen through the ranks and held the titles of head of neurology strategy in the US and head of Insights to Impact at UCB. In her current position, she oversees the commercial organization for rare diseases and develops launch strategies for new products in the rare disease market.

Outside of the pharma workplace, she was recognized as a Healthcare Businesswomen’s Association (HBA) rising star in 2018, and the following year, 

 placed her on its “40 under 40” list for her work developing UCB’s customer-facing field-market model.

Moran holds a PhD in neuroscience and physiology from New York University and a BS in biochemistry and molecular biology from Penn State University. Early in her career, she learned about the business side of the pharma industry by working alongside leadership at a small, startup company before moving on to UCB. She describes her current role as “a teeter-totter between science and business” that includes working in strategy, lifecycle management, and even sales.

Initially, however, Moran had very personal reasons for choosing to work in the life sciences and to focus on rare and orphan diseases.

“My uncle was diagnosed with a rare spinal cord disease when I was only about 10 years old,” she tells 

. “Just hearing the complexity of his path and the struggles for someone who is part of only a very small number of people who have that disease, when you have to pioneer to be diagnosed and be treated, motivated me to improve the system.”

Inspired by her uncle, Moran decided that she wanted to focus on rare diseases. She cut her teeth in the pharma industry working on potential treatments for autoimmune conditions lupus nephritis and myasthenia gravis, both considered orphan diseases.

Moran began her career in pharma at Aspreva Pharmaceuticals and credits the experience for guiding the course of her career. The company, which was founded in 2001, was still a startup during her time there. This provided Moran with a unique and wide-ranging training ground.

“The cool part about starting at a tiny startup was that I was employee 36. The head of marketing sat in one office, while the head of medical was nearby, as was the general manager,” she says. “It was interesting because I could learn about investor relations, regulatory, and marketing just by literally walking around the floor of our small company. That really gave me a great lens to understand all facets of pharma and that’s what’s really helped me to build to where I am today.”

One of the most important skills she learned during this time was storytelling. Moran says this helped her bring the science and clinical trial data alive, allowing her to present information in a way where everyone across the company could understand the rare diseases they were working with, even if they were highly complex and technical.

By the time she joined UCB 15 years ago, Moran took her experience working on the medical side and combined it with the lessons she learned on the business side. She explains that early on her career, she noticed that while there were treatments for the rare diseases she was focused on, patients often struggled to receive the proper treatment.

The more Moran learned about the business side, the more she realized that these patients were struggling for a variety of reasons and that there isn’t a one-size-fits-all solution.

“One of the insights that we use is that ‘the system isn’t built for me,’” she says. “The healthcare industry is not the most welcoming and easy thing to interact with, so the more that we can understand the complexity and depth of each patient, we can help them navigate the healthcare system better. They can get diagnosed quicker, treated quicker, and then be on a path to live at their ideals.”

These pursuits, notes Moran, advance the conversation to two topics that often come up in discussions about improving the modern pharma industry: diversity, equity, and inclusion (DE&I) and digital medicine.

Regarding the latter, Moran describes herself as a “digital evangelist.” According to her, it took pharma a bit longer than other industries to take on digitalization. She explains that pharma is a “data-rich industry” and the amount of data that can be collected, stored, analyzed, and presented using digital tools was “almost too much for us.”

“In the US, you can buy a variety of different types of syndicated data on claims, [electronic health records], and then you layer it with cool things like consumer data. [For example,] I know how many cat lovers are in Brooklyn.” Moran tells 

. “We weren’t quite ready to harness that depth in terms of pushing out solutions.”

Fortunately, the life sciences industry has begun to embrace a digital future, much to Moran’s delight. She says digital health tools allow her to use data and information in a much more efficient and powerful way to gain new insights, along with truly understanding the patients and stakeholders that she works with, and creating new solutions.

Moran points out as well that novel innovations in digital health are also helping to find new and harder-to-reach patients. Once again, her specific experience with treating rare diseases helped her search out new approaches, this time by identifying ways that new technologies could be used to track specific symptoms.

“An example is utilizing technology to identify biomarkers for disease progression,” explains Moran. “You can use your iPhone to measure any eyelid movement and voice changes. Those two things are indications of muscle weakness, which are hallmark for myasthenia gravis. We’ve partnered with a variety of tech firms to begin to pioneer, test, and roll out technologies to improve care and address those unmet needs.”

It’s clear that digital health and the possibilities it may unlock excite Moran. She points to the significant amount of practical application digital health is amassing in other industries, and believes those use cases can be adapted to pharma industry efforts in the space.

For example, she discusses the rise of marketing on social media, such as TikTok and Instagram, and how these advertisements can be focused on very specific markets. According to Moran, a similar approach can be taken when trying to identify patients for treatment or potential involvement in clinical trials.

“Some of the work that we’re pioneering is using these novel data sources to find patients and being able to have a new go-to-market model that leverages patient findings so that we are bringing solutions to patients much quicker than they would have in a non-digital supported ecosystem,” she says.

Not surprisingly, Moran’s interest in improving ways that pharma organizations find new patients extends to her views on the importance of DE&I. On its website, UCB describes Moran as a catalyst for change at the company when it comes to diversity. She was part of a team of employees who advocated for a DE&I council, along with a full-time diversity lead for the US.

When it comes to DE&I in the life sciences industry, Moran describes it as “essential,” especially in the context of patients and enrolling participants in clinical trials.

“Your patient populations need to reflect the land that each of these individuals are living in,” she stresses. “If you’re at the southern border of the US, it’s often Latinx and Spanish speaking patients. If you’re up in New York, you can roll the dice of 126 different countries that individuals may be from.” Moran also believes that rare diseases offer another look into the social determinants of health.

One of the problems that Moran wants to solve is the way that the healthcare system interacts with low-income populations. Part of her approach to fixing this issue is a push to include patients from these segments in clinical trials, to ensure that their needs are identified and addressed by the drug.

Challenging those pursuits, Moran notes, is how people from lower economic populations seem to be wary of the healthcare system, either out of fear or distrust. She says this can be another barrier to these patients participating in clinical trials, and it’s why she’s put significant focus on educating patients from these traditionally underserved populations. Her goal is to ensure that the clinical trials that she’s involved with truly represent the population of people who are actually living with thee disease or condition being worked on.

When asked about the struggles she’s faced navigating these challenges, Moran offers this advice: “It’s making sure that you slow down to go fast. It’s so easy just making sure that you get as many patients as possible so you can get your solutions out there,” she says. “You also must think, however, about onboarding a site in a neighborhood you haven’t done so in before. Maybe the doctors and [healthcare professionals] in that area haven’t run a clinical trial, so you might have to give them extra time to start up and be ready to do enrollment. They may need extra support in terms of having the right clinical trial coordinators and folks that can really be where patients are, that can show the right balance of demographics so that we have the data and information for folks with these diseases. Since the diseases I’m working on are rare, or even ultra-rare, it’s super hard to find patients for these clinical trials.”

It’s the unique challenges like these, inherent in rare disease R&D, that Moran has spent her career trying to overcome.

For example, she says that one of the diseases that she’s working on currently only has about 300 patients living with the disease. These small populations obviously makes it hard to recruit people for trials. Other conditions that she works on may ultimately have more patients, but many are often undiagnosed. This means that her UCB team has to rely on genetic testing, data, and analytic approaches to identify patients for some of these trials.

This further weaves in Moran’s fascination with digital health, which has pioneered the identification of genetic biomarkers, for example. These biomarkers allow researchers to identify patients who are still in the early stages of disease progression and haven’t been diagnosed yet, or are likely to develop the condition later in life.

While digital technologies have helped support her work, Moran is also mindful that not everyone is willing to embrace digital health, including some patients.

“It’s a double-edged sword. You must be tailored and customized, and your tools have to flex based on the patient preference,” she tells 

. That’s something that we’re learning in terms of designing patient solutions. Some folks want some SMS or text, some would like an email or a website. Then there’s some that don’t have access to technology and a paper enrollment form is what they’re looking for.”

While balancing these varied preferences, Moran says it’s important to use tools in digital health to help close the knowledge gaps in current treatment vs. right treatment, or patients being diagnosed or not. She believes there are many solutions drugmakers and their partners can tap into to close those gaps.

As an industry, pharma can’t do things alone,” says Moran. “When it’s around direct care delivery, there’s a pretty big distrust of pharma coming in with altruistic/holistic solutions, so you need to partner with patient organizations or tech companies.”

UCB, for example, has a collaboration with Microsoft around drug discovery and development, and, according to Moran, also works closely with patient organizations and patient advocacy groups. “Partnership is one of the key levers to the future, especially in rare diseases,” she says. “These aren’t disease states where you can just own a section, you have to lean in and go with the holistic disease. That’s a big area for me.”

Moran’s career may have started on the science and medicine side of the industry, but it has been her ability to merge those aspects with the critical business execution necessary to advance rare disease research that has ultimately shaped her success.

 is Pharm Exec’s editor and can be reached at


Executive Profile

Kimberly Moran, head of rare diseases in the US for UCB, started off working in medicine but quickly learned the importance of the business side of industry—and its role in helping improve the diagnosis and access paths for underserved patient segments.

Business and Passion

In January 2020, healthcare industry movers and shakers descended on San Francisco for the 38th Annual J.P. Morgan Healthcare Conference, the definitive Woodstock of healthcare. Who could have imagined that we would not return until January 2023. What will we be talking about?

The Inflation Reduction Act (IRA) became law in August and gives Medicare the power to cut prices and cap out-of-pocket spending for seniors on some drugs. The legislation will also require drug companies to pay Medicare a rebate if they raise prices faster than the rate of inflation. This will be tough to implement, which is why Congress allocated $3 billion for it.

That said, companies and investors are concerned about the likelihood of lower sales, reduced profitability, and fundamental shifts in R&D strategies. Some industry CEOs have said they have already initiated portfolio reviews through the lens of the IRA. While there is still significant uncertainty among industry leaders around how the law may be implemented and how it will affect their businesses, many have cited that it will shape their decisions to cut back or reshape their research. The IRA reduces the attractiveness of small-molecule innovation vs. biologics, which is unfortunate given that these are the lowest-cost therapeutic options. Biologics, or large molecules, tend to be far more complex and costly. The specific disincentive in the IRA for the development of small-molecule drugs is that they would be exempted from price negotiations for only nine years post-approval, compared to 13 for biologics. It is also likely to discourage investments in additional indications over the course of a drug’s lifespan, as the time for a return would be limited. Oncology is expected to be hit especially hard.

I’m sure there will be lots of questions and debate about the IRA at JPM; but given the standstill in Washington between Democrats and Republicans, the law itself is unlikely to change anytime soon.

These two areas have, and always will be, core to the growth strategies of the largest biopharma companies. But it is expected that the pace of dealmaking will accelerate (despite a potential recession) for a multitude of reasons. Those include an innovation renaissance across the smaller “target” biotechs and record levels of firepower (> $1.2 trillion, according to the annual Firepower EY report) across the acquiror universe, which also find these parties needing to address a looming growth gap with upcoming losses of exclusivity for revenues of about $225 billion beginning in 2025. This is complemented by a high level of distress among the target biotech companies. Many public and private organizations are currently valued below cash, and many have limited access to the capital markets. It is estimated that about 40% of the sector will have less than 12 months of cash by year end. The IPO market has been shut down for all of 2022 and follow-ons confined primarily to those companies generating positive clinical data, and even then, at highly dilutive valuations. Since its peak in February 2021, the biotech sector has gone through its longest and steepest bear market. Some very early-stage companies launched into the public markets during 2020 and 2021 funded through limited or no meaningful clinical milestones have seen share price declines of ~90%.

Will sparks fly during the week of the 41st Annual JPM Healthcare Conference this January 9-12? Could we see rotation out of value back into growth and biotech?

The reopening of the economy ushered in by vaccines and therapeutics fueled a rotation out of growth and into value stocks in anticipation of a V-shaped recovery, which we got. That ultimately led to the steepest Fed-led spike in interest rates in more than 40 years to tame the inevitable inflation, which, in turn, decimated valuations of long-dated assets.

Development-stage biotechs are the longest-dated asset class, and their stock prices fell precipitously in lockstep with the rise in rates and inflation. There is talk that a peak in rates and inflation could be in our line of sight as is a potential recession. If so, investors may rotate back into growth and biotech, specifically. If that pivot gets an additional nudge from an active M&A calendar, we could be setting up for some good news at JPM and a better year for biopharma in 2023.

is Founder, Barbara Ryan Advisors, and a member of Pharm Exec’s Editorial Advisory Board.

Will biopharma investment heat up and signal better fortunes for 2023? 

Pharmaceutical Executive-12-01-2022

Biopharma’s Untapped Value: The Quest to Reverse First-Launch Failure Trends

2023 Pipeline Report: Testing the Limits

Business and Passion

Back in Person, Sparks Could Fly at Upcoming J.P. Morgan Conference

Aligning Trust and Transparency in Brand Messaging

Pharma Needs to Look Internally for New Leadership

Seeking Concrete Solutions to Europe’s Supply Problems

Pandemic and Politics Shaped Pharma and FDA in 2022

Medical Affairs Uptick

Pharmaceutical Executive, December 2022 Issue (PDF)

Virtual Medical Affairs Audits: A Viable Alternative