Gene Therapies for Sickle Cell Disease: Expensive but Worth It

Sickle cell disease affects roughly 100,000 Americans and is more common among African American and non-Hispanic Black people [1]. About 20,000 suffer from recurrent vaso-occlusive crises (VOCs), making them ideal candidates for the novel gene therapies Casgevy (exagamglogene autotemcel, Vertex) and Lyfgenia (lovotibeglogene autotemcel, bluebird bio, rebranded as Genetix Biotherapeutics) [2]. Priced at $2.2 million and $3.1 million, respectively, these drugs are highly innovative and – we conclude – worth the high price tags if payers can figure out how to foot the bill.

Approved in December 2023, Casgevy is a CRISPR/CAS9-based therapy, the first of its kind. Its administration procedure is similar to that of a stem cell transplant and it is incredibly efficacious, with 93% of patients in the clinical trial remaining VOC-free 12 months after treatment [3]. Casgevy also boasts an approval in transfusion-dependent beta-thalassemia, a rare blood disorder that affects only 1,300-1,500 people in the US [4]. Lyfgenia is similarly efficacious and works via a lentiviral vector to insert a functional copy of the beta globin gene to increase the production of normal hemoglobin.

Both therapies demonstrate high clinical innovation when compared to the standard of care, hydroxyrurea, with a direct cost amortized over three years. Amortization is based off clinical data demonstrating that patients who achieve VOC-free status over 12 months remain VOC-free for approximately 3 years [5, 6]. This assessment may change as more long-term data becomes available. With the life expectancy of sickle cell disease patients being far shorter than for those without the disease, these therapies have the potential to substantially close that gap, with a University of Washington study finding a benefit of approximately 17 years of increased life expectancy from the gene therapies [7]. Our model captures a dramatic 85% reduction in mortality to align with this. These therapies are even more impressive when considering the high unmet need of sickle cell disease, in addition to the societal and indirect cost savings they may bring.

However, the issue of paying for these high-priced therapies looms large. An analysis conducted by the Institute for Clinical and Economic Review (ICER) in 2023 concluded that they are cost-effective at a price range of $1.5-$2 million [8]. At $2.2 million, Casgevy is pushing that limit, and at $3.1 million, Lyfgenia is well out of the range. With these steep price tags, it will be a challenge for payers to figure out how to pay for them, especially considering that a large percentage of the patient population is underserved and on Medicaid [9]. Currently, CMS has proposed an outcomes-based pricing scheme (CGT access model) that individual states can opt into. Only patients enrolled in Medicaid could benefit from the model, which began in early 2025.

This model has the potential to reduce the cost for states to bear, as CMS is the central negotiator for all states and will be providing federal funding for the treatment. States can choose which gene therapies to cover [10]. Based on our analysis, we believe that covering Casgevy is more reasonable than Lyfgenia, but having more options could be beneficial for patients, even with Lyfgenia’s black box warning for hematologic malignancy that demands long-term monitoring indefinitely [11]. Manufacturers will be encouraged to provide rebates and reimburse accordingly in cases where clinical performance falls short. The initiative will also be collecting data over eleven years, with an outcomes-based agreement term of one to six performance years, which will provide further insight into navigating these expensive gene therapies [12]. The model does not include private insurance plans for those not enrolled in Medicaid. Patients on private insurance plans may face additional requirements for treatment, such as meeting a specific threshold of number of VOCs per year, and a baseline level of decent health.

Gene therapies have limits; they are not foolproof cures. Not all cells can uptake the edits, there may be off-target gene editing effects, they are not effective for every patient, and immune system responses may limit efficacy and compromise health [13]. The treatment journey is also time-consuming, with the Casgevy website stating that it can take up to one year [14]. Since long-term data are not currently available, we must learn as we go, but it is clear that Casgevy and Lyfgenia are an important milestone in the cell and gene therapy space.

Keytruda Grabs its 42nd Approval in PD-L1+ PROC

Keytruda (pembrolizumab, Merck) received its 42nd approval from the FDA this Tuesday, February 10th based on the results from the phase 3 KEYNOTE-B96 trial, which looked at the blockbuster PD-1 inhibitor as an add-on to paclitaxel with or without bevacizumab in PD-L1+ platinum-resistant ovarian cancer (PROC). [1] This subset of ovarian cancer patients has developed resistance to standard platinum-based regimens. As a result, they receive non-platinum chemotherapy, such as paclitaxel, pegylated liposomal doxorubicin, or topotecan.

When compared to paclitaxel +/- bevacizumab, the Keytruda regimen showed improvements in survival, progression, and response while maintaining a comparable safety and convenience profile. Importantly, the mortality benefit is what stole the show: an impressive 30% increase in mOS over paclitaxel +/- bevacizumab (19.2 months vs. 14.0 months). [2]

Taking into account the cost impact of adding on Keytruda, the Clinical Innovation is clawed back slightly to a respectable 5.0% overall (Figure 1). Although Keytruda has seen higher levels of innovation elsewhere, such as its many NSCLC indications, a score of 5% typically suggests market differentiation and shows promise for Keytruda's use in this space.

This Clinical Innovation exhibited by Keytruda will increase in the coming years, as Keytruda is scheduled to lose exclusivity in 2028, which will slightly ease the cost burden.

[1] U.S. Food and Drug Administration. FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. February 10, 2026. Accessed February 12, 2026.

[2] Cortese T. Pembrolizumab combo significantly improves PFS/OS in recurrent PROC. CancerNetwork. October 18, 2025. Accessed February 12, 2026.

Plan for the Best, Prepare for the Worst - Handling Uncertainty in R&D

Where the Uncertainty Lies

Assets in mid to late-stage development are seldom immune to uncertainty surrounding their efficacy and safety profiles as well as that of their competitors. When considering these variables along with launch timing and the potential for reimbursement friction, traditional techniques such as conjoint analysis are rendered ineffective. Such circumstances require far more objective, dynamic, and future-proofed approaches.

A Data-Driven Approach

Using our unmet need framework, Equinox Group consistently quantifies the clinical improvement offered by a drug using a metric that we call Clinical Innovation. This measure has proven to be highly predictive of peak-year patient share and has been the basis of our analyses for over 30 years.

By objectively quantifying the Clinical Innovation of a new drug and all of its relevant competitors, we enable our clients to prepare for all possible scenarios that they will face during development and to seamlessly toggle between them.

Wargaming with Multiple TPPs

By quantifying the uncertainty in a given indication, we can understand its implications with remarkable accuracy.

Consider, for example, a chronic disease with three agents currently in the market. Working alongside the client, we come up with a base case, an upside case, and a downside case for their new drug, taking into account efficacy, safety, side effects, dosing, administration, price, and launch timing. Under the base case, the new drug achieves 20.3% share of drug-treated patients by the end of 2031. Under the upside and downside cases, it achieves 29.3% and 14.7% respectively. As a result, in a world where no competitors are launching in the coming years, we have bounded the share potential between 14.7% and 29.3%. By assigning probabilities to each of the three scenarios, a simple weighted average will yield the expected share by the end of 2031 under the assumed conditions. In this example the modeled probabilities of the base, upside, and downside cases are 71%, 21%, and 8%. This results in an expected value of 21.7% patient-share by 2031.

Figure 1: Launching without a threat

Introducing Competitors

By studying the different scenarios in Figure 1, it is clear that the client agent has moderate potential. Now, consider a highly innovative competitor, which we call Threat 1. With Threat 1 launching one year later than the client agent, it will have considerable, yet diminished, impact on the terminal shares. Now, the client agent 10.4% patient-share in the base case and 19.0% and 6.1% in the upside and downside cases respectively.

Using the same probabilities of 71%, 21%, and 8%, we get an expected value of 11.9% patient-share by 2031. These probabilities can be informed by input of the client organization and approximated through Monte Carlo simulations, which are easily implemented into our framework when handling uncertainty around all relevant product attributes including launch timing.

Analyses like this can be made as complex as needed, allowing for up to 15 different drug profiles, characterizing the variety of potential attributes of your drug as well as all relevant competitors.

Figure 2: Launching with a threat

What About When the Data Changes?

Whether it be new clinical data pertaining to your agent or any of its competitors, the dynamic nature of these models allows client organizations to change the relevant inputs within a matter of minutes with no additional cost. That means no need for funding 50 additional interviews with leading physician’s, no need for creating new stimuli, no guesswork, and no time wasted in order to obtain new patient-share estimates. 

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Equinox Group has fine-tuned these methodologies and others over the past 30 years to help biopharmaceutical companies handle challenges in R&D. Our specialties range from disease-area strategy and market access to patient share forecasting and patient flow modeling.

To learn more about our process, click here to schedule a meeting with one of our practice leaders.

Finding the Best R&D Opportunities

R&D leaders making investment decisions must rely on opportunity assessments from program advocates. Equinox Group offers independent analyses that allow decision makers to add an objective perspective to these discussions, leading to a fact-based conversation about the clinical and commercial merit of the various projects competing for R&D resources.

“But I don’t have TPPs, what can I do?”

We spend much of our time talking with clients about how good their TPPs look and what patient shares they can expect to achieve in order to guide indication prioritization. To read a case-study on how we do this, click here.

But what can we do for you if you don’t have TPPs yet?

The answer is a two-step process, which we call Disease Area Scan. First, we characterize the unmet medical need, epidemiology, and competitive intensity in all of the populations of interest. This allows for cross-indication comparisons that help identify which opportunities offer the greatest potential for commercial success. Next, we examine each of those opportunities individually, discovering what level of improvement is required in specific product attributes in order to achieve a certain level of Clinical Innovation and peak-year patient share. These analyses are grounded in peer-reviewed literature and hard clinical data, removing subjectivity and opinions from the equation.

Step 1: Characterizing unmet medical need, epidemiology, and competitive intensity

We begin our modeling process by diving into the most recent peer-reviewed literature pertaining to each indication, quantifying the level of unmet need under the current standard of care. See Figure 1 for a detailed breakdown of what we measure.

Figure 1: Factors we assess

These measures are then mapped onto a 0 to 5 scale to produce a single “unmet need score,” with a higher score indicating a higher level of unmet medical need.

Next, we align with the client organization on the epidemiology and competitive pipelines in each indication. We represent the latter by a probability weighted score indicating the expected number of head-to-head competitors that a drug will face at launch. We call this the “competitive intensity.”

Figure 2: Competitive intensity vs. unmet medical need

Looking at Figure 2, we can identify the most attractive opportunities, which are those with sizeable populations, considerable unmet need, and relatively low competition. Granted, two questions still remain. First, how would the specific drug need to perform in these populations in order to be successful? Second, in what indications do you realistically believe that you can achieve that performance?

Step 2: Using Heat Maps

In order to answer these questions, we can turn to a series of heatmaps, which guide development teams in understanding what levels of Clinical Innovation are achieved by specific efficacy and side effect profiles. Below in Figure 3, we will explore a situation where the current standard of care is pembrolizumab with a median progression-free survival of 6.9 months. We see that an improvement of 1 month in mPFS and a similar side effect profile will result in a 4.6% Clinical Innovation, which is slightly below the recommended 5% threshold. However, if the new drug also offered a side effect profile similar to that of crizotinib, it will achieve a 5.8% Clinical Innovation and likely have a favorable commercial outlook. (For this analysis, it was assumed that an improvement of one month in mPFS also led to an improvement of two months in mOS)

Figure 3: An introduction to heat maps

By focusing on relative improvements under the Equinox framework, development teams are able to identify indications where their agent has the potential to be competitive (those where Clinical Innovation 5-10%) and those where it could be a homerun (Clinical Innovation >10%). In situations where the clinical team is not ready to commit to specific efficacy values for their TPPs, this approach allows teams to prioritize those indications where they are more confident of “getting into the green”. These heat maps can be generated for a variety of attributes, allowing for a comprehensive and thorough analysis of potential products that projects a variety of scenarios. 

What About Share Potential?

While Clinical Innovation is a powerful predictor in itself, we don’t have to stop there. Combining the clinical innovation scores of hypothetical TPPs along with the corresponding competitive environment, unmet need, and epidemiology allows for the preliminary estimation of peak-year patient share using our Disease Target Assessment (DTA) framework. Given its dynamic nature, it is easy to conduct “what if” analyses with a variety of TPPs in each indication. Additionally, once TPPs are finalized, they are easily input into the model and adapted to continue to guide the R&D process. To read more about what is behind our analysis and how it predicts share, watch this quick video.

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Equinox Group has fine-tuned these methodologies and others over the past 30 years to help biopharmaceutical companies handle challenges in R&D. Our specialties range from market access and go/no-go decisions to patient share forecasting and patient flow modeling.

To learn more about our process, click here to schedule a meeting with one of our practice leaders.

Using Equinox Drivers Charts to Understand Fabhalta's Success in PNH

Paroxysmal Nocturnal Hemoglobinuria (PNH) is rare blood disorder estimated to have a global prevalence of 12 to 13 per 1,000,000 people [1]. This condition can potentially lead to kidney disease, hemolytic anemia, and even life-threatening blood clots [2]. Until the C5-inhibitor Soliris (Alexion, eculizumab) was approved in 2007, there were no approved therapies for PNH [3].

While Soliris, along with Alexion’s other C5 inhibitor, Ultomiris (ravulizumab, which was approved for PNH in 2018 [4]), are still considered standards of care, the market has grown with the approvals of Empaveli (Apellis, pegcetacoplan), Fabhalta (Novartis, iptacopan), and PiaSky (Roche, crovalimab). Using Equinox drivers charts can help us understand how these newer entries compare to Alexion’s drugs.

Select First Drug Soliris biosim Ultomiris Empaveli Fabhalta Piasky

Select Second Drug Soliris biosim Ultomiris Empaveli Fabhalta Piasky

Select two drugs above to see the drivers chart

Equinox characterizes a drug’s improvement relative to a previous standard of care or another drug with a Clinical Innovation (CI) score, which quantifies how much the new agent lowers unmet need in the indication. For frame of reference, products with >2% CI score are typically commercially viable, products with >5% CI score are commercially successful (top 3-4 in market), and products with >10% CI score are market dominators.

Fabhalta has a whopping CI score of 29.9% when compared to Ultomiris. Though Fabhalta being the first oral agent in this indication is an improvement on its own, its substantial efficacy benefits flow through to improve morbidity and mortality across the board. Although Fabhalta has the highest WAC ((Wholesale Acquisition Cost) among the PNH drugs in this analysis, this is offset by reductions in hospitalization and associated medical costs.

While Empaveli improves upon Ultomiris’s efficacy, it does not do so to the same extent Fabhalta does. Additionally, while Empaveli can be administered at home, the frequency of administration is increased, offsetting some of its convenience benefit. In most cases, a 10.0% CI score would be expected to be a market dominator, but because it still falls far short of Fabhalta, this would be an exception.

Finally, although Piasky is more convenient than Ultomiris, this is not enough to overcome its marginally reduced efficacy at the current WAC. We do not expect it to be competitive in this market, especially against newer drugs that reduce unmet need further, such as Fabhalta and Empaveli.

Soliris 2007 reflects Soliris WAC at launch; all costs inflated to 2025 USD.

Equinox also acknowledges the approval of Voydeya in this indication, though it was not included in this analysis due to it being approved as an add-on therapy for Soliris or Ultomiris, not a monotherapy.

Measuring Risk in R&D

The Problem

It is no secret in the biopharmaceutical industry that a new drug’s clinical improvement is strongly predictive of the share of patients it achieves. Consequently, drugs that offer little clinical improvement expose developers to commercial risk.

Many organizations, while aware of this problem, continue to lack a proven methodology to identify and quantify that risk. This exposes them to the possibility of advancing undifferentiated drugs that will experience low market access and vulnerability to future competition.

The Solution

Equinox Group has quantified the relationship between clinical improvement and patient share by comparing the magnitude of improvement delivered vs. share achieved in the real world in a large set of historical drug launches. Clinical improvement reflects advances in efficacy, safety, tolerability, dosing, and patient outcomes. Our metric for clinical improvement includes all of these domains and measures the percent reduction in medical need the new drug offers relative to the standard of care. We call that measure of improvement  “Clinical Innovation”.

Measuring Clinical Innovation: A Data-Driven Approach

For 30 years, Equinox Group has used a validated, data-driven approach to measure the clinical innovation offered by new drugs across hundreds of indications. See this two-minute video explanation:

The Link to Commercial Potential

Over many years we have re-evaluated the relationship between clinical innovation and patient share; it has been remarkably stable over time. Below is a table of historical drug launches and where they score in the Equinox Group framework.

As a rule of thumb,

• High Innovation: Drugs that offer 10% or more clinical innovation nearly always dominate the branded segments of their markets.

• Medium Innovation: Drugs with 5% to 10% innovation usually compete well.

• Low Innovation: Drugs with 0-5% improvement are in a gray zone and may be seen as undifferentiated, especially by payers.

• Lack of Innovation: Drugs with negative clinical innovation nearly always get low patient shares and disappointing sales.

How Much Clinical Innovation is Enough?

The clinical attributes anticipated in early R&D programs are rarely realized by the end of development. As time goes on, assets often acquire “warts,” whether it be unexpected side effects, lower than expected efficacy, or both. Programs that start with modest clinical aspirations are likely to offer unacceptable levels of innovation at launch.  We call this phenomenon “attribute drift.”

We recommend that drug development teams aim to achieve clinical innovation of at least 5% to reduce exposure to attribute drift and the commercial risks described in the beginning of this paper. Our tools allow teams to tie the expected clinical attributes of a new drug first to its level of clinical innovation, and then to patient share to forecast revenue potential.

The Take-Home

Equinox Group’s proven method to measure clinical innovation and predict peak-year patient share for target product profiles is accurate.  It’s also less expensive, more flexible, and quicker to execute than conventional market research-based techniques.  We use this approach to inform decisions about individual programs (pipeline and BD), to help therapeutic area teams set aspirations, and to inform R&D portfolio assessments.

Who Are We?

Since 1995, Equinox Group has provided analytics to support R&D decisions at biopharmaceutical firms, assessing the potential of drugs from discovery to launch. Our validated techniques will save you time and money, as well as overcome the deficiencies of traditional market research.

We have evaluated thousands of drug profiles across hundreds of indications in oncology, immunology, rare diseases, cardio-metabolic disorders, infectious disease, neurology, pulmonology, urology, ophthalmology, and endocrine disorders. We also have tailored methods to solve the unique analytical challenges that arise in oncology and rare diseases.

Using this methodology, we have developed a suite of tools to inform whatever R&D decisions you’re facing in any stage of development, including: setting indication priorities, supporting go/no-go decisions, assessing market access and pricing potential, share forecasting, and patient flow modeling.

How Equinox Group Models Drugs in R&D: The Case of Alecensa in 1L ALK+ NSCLC

We routinely share our view of new drugs coming to the market; for instance, a few months ago, we posted an article detailing top-line results of an analysis of Enhertu in 1L HER2+ metastatic breast cancer.

This article shows in detail how Equinox arrives at a peak share estimate for a new drug treatment, using the example of alectinib (Alecensa, Roche/Genentech) in 1L ALK+ non-small cell lung cancer (NSCLC). Alecensa was approved in this indication 8 years ago; we’ll show how our methodology predicted it would achieve 60% peak share using publicly available data and our Disease Target Assessment framework.

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The Framework

Equinox Group’s Disease Target Assessment (DTA) model quantifies the level of medical need in the target population based on peer-reviewed literature. This framework characterizes the adequacy of the current and possible future standards of care (SOCs) to serve as a benchmark for evaluating client product profiles.

We start by characterizing unmet medical need within each defined patient population, quantifying unmet needs in these product attributes:

• Efficacy

• Safety/tolerability

• Dosing

• Price

as well as key elements of the burden imposed by the disease:

• Mortality

• Morbidity (pain, chronic disability, hospitalization, and HRQOL)

• Non-drug health care costs

For each domain and subdomain, we use consistent utility functions to derive a score on a 0-5 scale (with 0 representing no unmet need and 5 substantial unmet need). Each domain has a fixed weight based upon its importance, as verified through regression analysis of launched agents. The sum of the weighted scores measures the total unmet medical need for patients treated with the profiled therapy.

Through validation against actual market performance, Equinox has demonstrated that the Clinical Innovation of a new drug (or regimen) offers reliable insight into its ability to compete. A few rules of thumb hold up surprisingly well in projecting a new drug’s commercial outlook:

• Drugs with 10%+ Clinical Innovation nearly always dominate their segments – we consider agents with 10%+ Clinical Innovation to be highly innovative

• Drugs with Clinical Innovation between 5% and 10% typically achieve good patient share – they are moderately innovative

• Drugs with Clinical Innovation below 5% are typically seen as poorly differentiated, especially by payers – these drugs have low innovation

Clinical Innovation and competitive intensity are key drivers of share; our DTA models enter these two inputs into an algorithm derived from a regression analysis of actual market performance to estimate peak-year patient share. Comparing our share predictions to observed peak-year shares, Equinox Group’s oncology-specific regression has a strong R-squared value of 83%.

The DTA methodology is rigorous and dynamic. The Excel-based model we deliver allows for instantaneous updates of inputs and outputs. All sources are well-documented in comments throughout the model, with a bibliographic sources sheet included as well.

Key steps in an Equinox DTA Project

1. Define the distinct patient population(s) of interest

2. Characterize disease burden within each patient population

3. Identify and characterize standard(s) of care

4. Model the market entrant/TPP

5. Analyze the developmental pipeline to quantify the expected future level of competition

6. Estimate the number of addressable patients in the US and key European markets

To support the modeling, Equinox Group also conducts a handful of interviews with academic medical experts to explore their views on pipeline agents, treatment paradigms, and key unmet needs.

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The Clinical Sheet

Equinox Group begins by characterizing the key clinical attributes of the SOC(s). We can then use an identical rule set to model client TPPs. For clients who do not yet have any TPPs, we can help model plausible scenarios for profiles.

In 1L ALK+ NSCLC, the SOC prior to alectinib was crizotinib. (Models normally carry two extra slots to model alternative or future SOCs as needed.)

The key clinical domains are shown in the figure below.

Starting in the efficacy domain, we enter peer-reviewed clinical data for the SOCs. Client TPPs are judged along the same lines. In oncology, key efficacy inputs are:

• overall survival,

• progression-free survival, and

• response rates (partial, complete, and overall)

All inputs are explained in accompanying comments within the Excel file. Academic literature is clearly cited, and any necessary assumptions are explained.

Key safety data are gathered from SOC labels and relevant published trials.

Boxed warnings, frequent or inconvenient patient monitoring, and contraindications and pregnancy warnings (when appropriate) are all taken into account.

Grade 3/4 adverse events are modeled and individually weighted based on their severities (e.g., hyponatremia has a lower impact on unmet need than neutropenia). When substantial adverse event data/hypotheses are available for a TPP, we can model the rates of each event. Alternatively, we can model a simple percentage improvement over a comparator profile (e.g., 20% reduction in the rate of each AE seen in the crizotinib side effect profile). In the example below, full side effect data were available.

The drug or regimen’s convenience score is calculated via a consistent method. Common dosing methods, frequencies, and locations are pre-populated in drop-down menus. The model allows for multi-drug regimens to be modeled, even when combining IV and oral therapies. In this example, each profiled drug is an oral monotherapy.

Finally, the drug or regimen’s annual cost is calculated using U.S. WAC pricing. We use WAC values because they allow fair, transparent comparisons and because net prices are not widely visible.

When patients are on treatment for less than one year, the cost calculation is restricted to time on treatment. In the example below, median time to progression is 10.9 months, so only that fraction of the year is entered in “intended days of therapy”.

The Unmet Need Sheet

The data from the Clinical sheet flow into the Unmet Need sheet (see below); the core clinical assumptions each have their own sub-domain under product need.

Equinox Group staff gather peer-reviewed data on disease burden (disease seriousness and disease cost), and the consistent utility functions are applied in Excel.

Baseline disease seriousness and costs values come from relevant academic literature, and improvements in efficacy flow through to reduce need in these domains.

In this example, alectinib is more efficacious (thus the lower Efficacy score) and has a cleaner side effect profile than crizotinib. Despite a minor convenience disadvantage, its product need score is significantly lower.

The advantage in overall survival is reflected in a lower mortality score.

Advantages in progression-free survival and response rates reduce morbidity, indirect costs, and non-drug direct costs.

These benefits in indirect and non-drug direct costs partially offset alectinib’s higher price.

The weighted sum of these domain-specific unmet need scores equals a product’s total unmet need score. Overall, total unmet need is lower with alectinib than with crizotinib in 1L ALK+ NSCLC, indicating a better therapeutic option.

Drivers of Innovation

We call the reduction in total unmet medical need is called "Clinical Innovation". We graphically display Clinical Innovation using a Drivers chart.

The gold bars to the left and right of the chart represent the unmet need score under the SOC (crizotinib) and entrant (alectinib), respectively.  Scores range from 0-5 with 0 representing no unmet need. As with any waterfall chart, the intermediate green and red bars represent improvements and detriments, respectively, in domain-specific unmet need.

In the above figure, alectinib is shown to reduce total unmet medical need by 23.2%, with more than two-thirds of its improvement coming from efficacy advantages, and its direct cost impact clawing back <1% of its Clinical Innovation. (The percentages on the chart show the contribution of each domain to that 23.2% overall improvement.)

The Clinical Innovation score of 23.2% is highly impressive. Recall our rules of thumb: products with unmet need improvements of >2% are typically commercially viable, >5% are commercially successful (top 3-4 in market), and >10% are market dominators.

The Competitive Environment

Equinox conducts a thorough review of the developmental pipeline using publicly available sources, such as clinicaltrials.gov and sponsor websites. This pipeline is reviewed by physician experts to ensure nothing is missed, and client competitive intelligence is welcomed.

Each pipeline agent is assigned a probability of launch based upon its phase of development and recent data on success probability by phase and therapeutic area. Competitors are also assigned an angle of impact – how directly (25%-100%) will the entrant and the pipeline agent compete with each other?

We call the sum product of these factors “Competitive Intensity”, a probabilized headcount of competitors the entrant will face at launch. A competitive intensity rating of 319%, as shown below, is roughly comparable to three direct competitors at launch.

The Commercial Sheet

Seeing a profile’s projected peak-year share is as simple as one click. Selecting the SOC at launch in the blue cell will automatically update the profile’s clinical innovation score which, alongside competitive intensity, are entered into the Equinox Share Predictor. The Commercial sheet also displays key figures such as unmet need scores with the SOC and entrant, diagnosed prevalence of the indication in the U.S., and the annual cost of the profile.

Given a Clinical Innovation score of 23.2% and a competitive intensity rating of 319%, Equinox Group’s regression-validated algorithm projects a peak-year patient share of 60% for alectinib in 1L ALK+ NSCLC.

Each entrant’s share call compares its unmet need score to that of a chosen SOC and factors in the estimated number of competitors at launch. In this example, product attributes for potential new competitors are not evaluated in calculating peak share. As a further product offering, Equinox builds forecasts that capture the impact of competing entrants’ clinical attributes and launch timing to produce realistic forecasts of share over time.

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Conclusion

The easy-to-use Excel-based DTA model allows clients to war-game scenarios for input values that aren’t certain yet (such as mature overall survival data) and instantly see how those alternatives affect Clinical Innovation and patient share estimates.

Interested in learning more? Click here to send us a message or to schedule a meeting with one of our practice leaders.

Equinox Group’s proven method to measure clinical innovation and peak-year patient share for new products is accurate, less expensive, more flexible, and quicker to execute than conventional market research-based techniques. We use this approach to inform decisions about individual programs (pipeline and business development), to help therapeutic area teams set aspirations, and to inform R&D portfolio assessments.

A project of this nature typically delivers results in around 6 weeks. We support our models for 24 months from kickoff and can help socialize the methodology and results within your organization.

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About Equinox Group

Since 1995, Equinox Group has provided analytics to support R&D decisions at biopharmaceutical firms, assessing the potential of drugs from discovery to launch. Our validated techniques save time and money—and they overcome several deficiencies of traditional demand studies.

We have evaluated thousands of drug profiles across hundreds of indications in oncology, immunology, rare diseases, cardio-metabolic disorders, infectious disease, neurology, pulmonology, urology, ophthalmology, and endocrine disorders. We also have tailored methods to solve the unique analytical challenges that arise in oncology and rare diseases.

Using this methodology, we have developed a suite of tools to inform whatever R&D decisions you’re facing in any stage of development, including: setting indication priorities, supporting go/no-go decisions, assessing market access and pricing potential, share forecasting, and patient flow modeling.

What indications should we focus on?

Drugs with utility across multiple patient populations have the potential to become major cash cows for biopharmaceutical companies. To tap this potential, companies must carefully select which indications to prioritize. This decision can be the difference between establishing a new brand that becomes a pillar of a company’s success and having consistently underperforming sales. The ideal choice is one where high medical need exists in a sizeable population, the asset promises to offer significant improvement, and there is relatively low competition. (Probably no indication checks all of these boxes perfectly.)

Equinox Group provides analytical decision support to development teams making indication prioritization decisions by quantifying these characteristics for each opportunity.

Figure 1 shows how key commercial factors compare across candidate indications for a new oncology therapy, which we call Product X.  Perhaps the most important of these—and the hardest to characterize consistently—is the level of improvement the drug would offer over the standard of care (SOC), a chief driver of patient share (more on share below).

We use a rigorous technique to quantify that improvement, which we call “Clinical Innovation”. Using real world market performance, we have observed that the following general rules hold up remarkably well:

• Drugs with 10% or greater Clinical Innovation typically dominate their segments

• Drugs with 5 to 10% Clinical Innovation achieve good patient share

• Drugs with less than 5% Clinical Innovation typically struggle; they impose high risk on the developer

Figure 1: Clinical Innovation, Population Size, and Medical Need: A New Drug in 8 Indications

Product X is highly innovative in 2L CRC (a large population), as well as in 2L TNBC and 1L ALK+ NSCLC.  It is also moderately innovative in 1L and 2L melanoma, and 2L pancreatic cancer.  In 2L prostate cancer, however, the drug’s Clinical Innovation is well below the 5% threshold, suggesting Product X will be approvable but not be highly competitive in this population.  In 3L melanoma, Product X’s Clinical Innovation is slightly below the desired 5% mark, but approval here may be helpful in pursuing 1L and 2L, larger patient segments where Product X is more innovative. These indications have moderate-to-high need at baseline, forming two tight groups on the high end of our unmet need scale.

With all of this in mind, we can transform our view to consider the competitive intensity in each population rather than the level of unmet medical need under the SOC. Below in Figure 2, indications are located by the competitive intensity faced by Product X as well as clinical innovation, with bubble size still indicating patient population size. Note that a lower score on the y-axis implies less competition, meaning that in indications located in the upper right, Product X offers high clinical innovation and has low competition.

Figure 2: Clinical Innovation, Population Size, and Competitive Intensity: A New Drug in 8 Indications

As we can see, the indications are once again separated into two groups: those with moderate competitive intensity (3 to 4 expected direct competitors at launch) and those with higher competitive intensity (5 to 6 competitors).

Additionally, Equinox has developed a regression equation that predicts peak-year patient-share as a function of two of the factors described here; the level of Clinical Innovation and the number of competitors.

Table 1 gathers the key commercial factors presented above into one view, including the corresponding peak-year patient share estimates in the indications.

Table 1: The Complete View

*Undifferentiated from SOC

From our assessment of the clinical innovation in each indication, it is already clear that 1L ALK+ NSCLC, 2L CRC, and 2L TNBC offer good commercial opportunities. But which of them is the best? And what about all the others? Taking into account the other commercial factors, we notice that while 1L ALK+ NSCLC faces moderate competition and has the highest clinical innovation, it ranks as the smallest population with the lowest unmet medical need. Therefore, it’s not going to provide the best revenue potential. Likewise, in 2L TNBC, there is a relatively low barrier to entry and a high unmet need, but the population size also restricts potential gains.

In 2L CRC, the moderate unmet need and large population size make it the best opportunity among the eight indications. While the competitive intensity is high, a clinical innovation of 11.3% should adequately insulate Product X from the competition and results in significant patient share in a sizable population. Due to its size, an initial approval in this indication will potentially help the asset owner manage development costs in the other indications.

These three indications (ALK+ NSCLC, 2L TNBC, and 2L CRC) also have the potential to create a “halo effect” where payers and prescribers view Product X more favorably in other indications due to its previous success. This may prove helpful when pursuing 1L & 2L Melanoma and 2L Pancreatic, all of which are valuable opportunities in this assessment. All things considered, Product X offers substantial revenue and growth potential, if managed properly.

Finally, the analytics described here also include a basis for comparing pricing potential across the candidate indications. To keep this introduction to the techniques brief, we have not included that analysis here, but for those interested in how a pricing potential assessment can be added to the outputs, see this example.

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We have fine-tuned these methodologies and others over the past 30 years to help biopharmaceutical companies handle challenges in R&D. Our specialties range from market access and go/no-go decisions to patient share forecasting and patient flow modeling. To learn more about our process, click here to schedule a meeting with one of our practice leaders.

Journavx, a vast improvement over opioids in moderate acute pain

Journavx’s clinical data in its first approved indication suggest it will be a game-changer in moderate acute pain management as it reduced medical need by more than 15% compared to hydrocodone + acetaminophen. (Figure 1) For reference, new drugs with 10%+ innovation over the standard of care generally achieve significant patient share. (Figure 2)

Figure 1: Drivers of Journavx's Clinical Innovation

Figure 2: Understanding Clinical Innovation

Journavx (suzetrigine), a sodium channel blocker from Vertex Pharmaceuticals, was approved on January 30, 2025 in moderate to severe acute pain, based on a pair of clinical trials that compared suzetrigine to a low dose opioid, 5 mg hydrocodone bitartrate in combination with 325 mg acetaminophen (HB/APAP), in patients that underwent abdominoplasty or bunionectomy. In these trials, suzetrigine offered reduced side effects while of course lacking the black box warning and schedule II drug status of hydrocodone. [1] These improvements, along with a slight boost from less frequent dosing, result in a substantial benefit in safety and convenience over HB/APAP and account for all of Journavx’s clinical innovation in Equinox Group’s analysis.

In addition to these strong advantages, suzetrigine held its own in terms of efficacy, with an improvement over placebo in the time-weighted reduction of pain intensity similar to that of HB/APAP (10% improvement vs. 11% in the HB/APAP group) in a pooled analysis of the two studies. The higher cost of suzetrigine claws back some of the benefits, but the net impact is a clinical innovation score of 15.3%, which is characteristic of a market-dominator. [2, 3]

Given the ongoing opioid epidemic in America, addiction free pain relief remains a significant unmet need. In 2024 alone, it was estimated that 4.8 million Americans had an opioid use disorder in the past year and 7.6 million had misused prescription opioids over that same period. [4]  While the current clinical importance of these medications is undeniable, it has long been agreed upon that the development of an alternative to opioids, especially for populations only experiencing moderate pain, is essential.

While Journavx proves significantly advantageous in the management of acute pain following minor surgeries, it remains to be seen how it stacks up against opioids in populations with more severe pain. In addition to exploring this further, Vertex is currently conducting a trial in diabetic peripheral neuropathy, suggesting we may see a future label expansion into the chronic pain space as well. But given these impressive initial results, Equinox Group suspects that suzetrigine will carve out a sizable share of the overall pain market.

[1] JOURNAVX Prescribing Information. FDA. Accessed July 11, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219209Orig1s000lbl.pdf

[2] Vertex Pharmaceuticals Incorporated, Evaluation of Efficacy and Safety of Suzetrigine for Acute Pain After an Abdominoplasty. ClinicalTrials.gov identifier: NCT05558410. Last updated: July 1, 2025. Accessed August 29, 2025. https://clinicaltrials.gov/study/NCT05558410

[3] Vertex Pharmaceuticals Incorporated, Evaluation of Efficacy and Safety of VX-548 for Acute Pain After a Bunionectomy. ClinicalTrials.gov identifier: NCT05553366. Last updated: December 16, 2024. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT05553366

[4]  Substance Abuse and Mental Health Services Administration. (2025). Key substance use and mental health indicators in the United States: Results from the 2024 National Survey on Drug Use and Health (HHS Publication No. PEP25-07-007, NSDUH Series H-60). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration.https://www.samhsa.gov/data/sites/default/files/reports/rpt56287/2024-nsduh-annual-national-report.pdf

Enhertu is poised to dominate first-line HER2+ breast cancer

Equinox Group’s analysis of the Enhertu + Perjeta combination in first-line HER2+ breast cancer predicts a peak-year patient share of 46% in that setting. Our finding is based on initial results from the Destiny-Breast09[1] trial and the expected competitive environment. FDA approval in first-line is likely by the end of 2025[2].

The core of our analysis compares the net clinical improvement of the Enhertu regimen vs. the current standard of care, Perjeta + Herceptin + paclitaxel. Using our rigorous, data-driven methodology, we find that the Enhertu regimen reduces medical need by 14.6%.

History shows that drugs with a 10% or greater reduction in need typically go on to dominate their segment. Enhertu’s improvement in this population is similar to Tagrisso’s advantage in first-line EGFR+ NSCLC.

The graphic quantifies that net clinical improvement, and shows the contribution of each clinical attribute. The biggest driver is efficacy, primarily progression-free survival (40.7 months for the Enhertu regimen vs. 26.9 months for the SOC). Because the median overall survival data is not yet mature, we have made a conservative assumption about that value for Enhertu. Moreover, the Enhertu regimen spares patients paclitaxel, greatly reducing the frequency of neutropenia and offering a cleaner side effect profile. While the Enhertu regimen costs more, that modest disadvantage is overwhelmed by the clinical benefits.  

[1] Tolaney et al. 2025

[2] Daiichi Sankyo Press Release, July 2025