TROP2 ADCs: A Major Innovation for 1L TNBC

Gilead’s Trodelvy has made a name for itself in breast cancer, but recently Daiichi Sankyo AstraZeneca’s competing TROP2 ADC, Datroway, has beaten Trodelvy to market in 1L TNBC, a patient segment with traditionally no treatment options aside from chemotherapy alone. Approved one month apart from each other, Datroway has the stronger data, but Trodelvy has a broader label and physician experience on its side.

Approval Histories

In April 2020, Immunomedics’ novel TROP2 ADC, Trodelvy (sacituzumab govitecan-hziy), was granted accelerated approval for the treatment of relapsed or refractory triple-negative breast cancer (R/R TNBC), making it the first ADC approved by the FDA for this indication. Gilead went on to acquire Immunomedics and Trodelvy six months after its initial approval. Trodelvy was granted full approval in R/R TNBC in April 2021 and accelerated approval in pre-treated HR+/HER2- metastatic breast cancer in February 2023. Along the way, Gilead picked up and subsequently voluntarily withdrew an accelerated approval for the ADC in metastatic urothelial cancer.

No new TROP2 ADC had been approved since Trodelvy until January 2025, when Daiichi Sankyo and AstraZeneca’s Datroway (datopotamab deruxtecan-dlnk) was approved in pre-treated HR+/HER2- metastatic breast cancer, almost two years after Trodelvy’s approval in this indication. Datroway’s next approval came in June 2025 for pre-treated EGFR-mutated non-small cell lung cancer (NSCLC), an accelerated approval based on response rates from a pooled subgroup analysis of a broader population, beating Trodelvy to launch in lung cancer.

Clinical Data Summary

Now, within just one month of each other, the two TROP2 ADCs have each gained approval in previously-untreated TNBC, a patient population which to date has had chemotherapy as their only option in immunotherapy (IO)-ineligible patients. Datroway was first to be approved in 1L TNBC ineligible for IO, boasting an impressive 43% reduction in disease progression or death (PFS HR 0.57, p<0.0001) and 21% reduction in mortality, statistically significant at the 5% threshold (OS HR 0.79, p 0.0290) [1]. Trodelvy, just one month later, received approval regardless of a patient’s PD-L1 status, a broader population than that of Datroway. Trodelvy’s overall survival data are immature across both of its 1L TNBC populations, but its PFS benefits are still significant. In the PD-L1-negative/IO-ineligible segment, Trodelvy reduced the risk of disease progression or death by 38% (PFS HR 0.62, p<0.001)[2] compared to Datroway’s 43% reduction. For patients with a PD-L1 combined positive score (CPS) ≥ 10, Trodelvy + Merck’s Keytruda (pembrolizumab) boast a PFS HR = 0.65 (p<0.001) when compared to Keytruda + chemotherapy [3].

Equinox Group’s Analysis

Compared to their respective control arms in the IO-ineligible population, Datroway looks highly innovative using Equinox Group’s Disease Target Assessment (DTA) framework, reducing medical need by 10.6%; historically, improvements ≥10% become leaders in their market segments.

Clinical Innovation is displayed graphically in the below waterfall chart, where the unmet need score of the comparator regimen (chemotherapy) is represented on the left and the entrant (Datroway) on the right. Unmet need is scored on a 0-5 scale, with lower scores representing less unmet medical need. The individual green and red bars total to a regimen’s Clinical Innovation score.

Figure 1: Drivers of Clinical Innovation – Datroway in 1L TNBC ineligible for IO

In comparison, Trodelvy’s weaker PFS benefit and immature (and insignificant at this time) OS data produce a less favorable gain, with a net Clinical Innovation score of -0.7%, essentially looking equivalent to chemotherapy.

Figure 2: Drivers of Clinical Innovation – Trodelvy in 1L TNBC ineligible for IO

Compared against each other, Datroway’s Clinical Innovation score is 6.7%, significantly differentiated against Trodelvy.

Figure 3: Drivers of Clinical Innovation – Datroway vs. Trodelvy in 1L TNBC ineligible for IO

Trodelvy’s story is rosier in the PD-L1-positive cohort, delivering a 7.2% reduction in unmet medical need when combined with Keytruda, compared to chemotherapy plus Keytruda—a competitive Clinical Innovation score.

Figure 4: Drivers of Clinical Innovation – Trodelvy in 1L TNBC, PD-L1-positive

Share Prediction

With the innovation scores above and low levels of existing competition, Equinox Group predicts that Datroway could achieve a 56[JL1] [KC2] [JL3] % peak share in the IO-ineligible population and that Trodelvy could achieve a 60[JL4] [KC5] % peak share in the PD-L1-positive cohort.

Datroway is currently in clinical development for the treatment of PD-L1-positive 1L TNBC, in combination with AstraZeneca’s in-house PD-L1 inhibitor, Imfinzi (atezolizumab), which to date has no approvals in breast cancer (this trial, TROPION-Breast05 is expected to read out by mid-2027). Both Datroway and Trodelvy are trialing in pre-metastatic TNBC, as well, with Datroway’s trial expecting to read out mid- 2027 and Trodelvy’s by the end of 2028.

What remains for this field is the promise of yet another TROP2 ADC, Merck’s sacituzumab tirumotecan (sac-TMT). In its phase 2 OptiTROP-Breast05 trial, Sac-TMT demonstrated improved response rates over its in-class competitors across the PD-L1 spectrum.

[1] Dent et al. 2026 (TROPION-Breast02)

[2] Cortes et al. 2025 (ASCENT-03)

[3] Tolaney et al. 2026 (ASCENT-04/KEYNOTE-D19)

TP53, the most altered gene in oncology

With the evolution of RAS inhibition, ambitions are high and drug developers are looking for the next big target. TP53 is a noble contender, as it is the most altered gene across solid tumors with no approved targeted therapies and little progress made thus far. The RAS pathway spent four decades on the same “undruggable” list as TP53. Now, KRAS G12C inhibitors have been on the market for five years and pan-RAS and allele-specific agents are in development that, together, could address ~90% of pancreatic cancers, representing a major paradigm shift.

Below are cancers with the top 10 percent prevalences of TP53 alteration.

Lifyorli Approved in Platinum-Resistant Ovarian Cancer Thanks to a 35% Reduction in Mortality

Lifyorli (relacorilant, Corcept Therapeutics) received its first approval on March 25th based on the results from the phase 3 ROSELLA trial, which looked at the Corcept agent as an add-on to nab-paclitaxel in platinum-resistant ovarian cancer (PROC) patients who have received prior bevacizumab. [1] These patients have limited treatment options and a mortality rate in the first year of platinum-resistant disease that is 16 times higher than that of their age-matched peers. Recent FDA approvals have emerged in subsets of PROC patients with actionable biomarkers, but little options remain for patients without them. As a result, these patients will typically receive non-platinum chemotherapy, such as paclitaxel, pegylated liposomal doxorubicin, or topotecan. [1]

When added onto nab-paclitaxel, Lifyorli offered over 4 additional months of survival compared with nab-paclitaxel alone. (16.0 vs 11.9, HR = 0.65) [1] This substantial benefit helps to meaningfully address the most substantial unmet need of this disease. However, the regimen did not offer the same magnitude of improvement in progression-free survival and overall response, only scoring one additional month of PFS (6.5 vs 5.5) and not achieving a statistically significant difference in the secondary endpoint of overall response rate (36.9% ORR vs 30.1%, p=0.17). [2] Together, these attributes make up an interesting efficacy profile, as an OS improvement more than 4x the PFS improvement of a given regimen is highly uncommon.

When taking into account the modest drawback of increased side effects, Lifyorli achieves a solid 5.8% clinical innovation when compared to nab-paclitaxel. While this is not a blockbuster score, it is no doubt a meaningful efficacy improvement that will make this drug competitive.

Figure 1: Drivers of Clinical Benefit

[1] U.S. Food and Drug Administration. FDA approves relacorilant with nab-paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Published March 25, 2026. Accessed April 7, 2026.

[2] FDA approves relacorilant plus nab-paclitaxel for platinum-resistant ovarian cancer. OncLive. March 25, 2026. Accessed April 7, 2026.

Oveporexton Could be a Game-changer for Narcolepsy Type 1

Narcolepsy is a rare neurological disorder that affects an estimated 200,000 Americans [1], and about half of those people have narcolepsy type 1 (NT1) [2]. While both NT1 and NT2 cause sleep attacks and excessive daytime sleepiness, NT1 also causes cataplexy: episodes of sudden muscle weakness often triggered by intense emotions. Not only does NT1 severely impact quality of life, but it can also be dangerous when cataplexy episodes or sleep attacks occur during activities such as driving or operating machinery [3].

In February 2026, the FDA accepted the NDA for oveporexton, Takeda’s investigational agent, and granted it Priority Review. Instead of simply managing symptoms, oveporexton is a potentially first-in-class OX2R-selective agonist that targets the orexin deficiency that causes NT1 [4].

Oveporexton yields an exceptional clinical innovation score of 20.4% over standard-of-care Xywav when it is priced at a modest premium. Based on currently available data, we view oveporexton as a more efficacious and convenient option, and, if launched at this price point, expect it will take a commanding lead of the NT1 market.

The Problem with Primary Market Research

Pharmaceutical companies spend millions on primary market research (PMR) every year — and often walk away with the wrong answer. PMR plays a genuine role in the R&D process: interviews with physicians provide insight into treatment paradigms, patient types and “journeys,” and reasonable expectations for the future of a disease. Equinox Group routinely conducts such interviews to inform our modeling efforts. This type of research has been a staple in the industry for decades, making it something people at all levels of organizations understand and can use to extract actionable insights. So, what’s the problem?

Too often, PMR is asked to be something it is not: a replacement for rigorous techniques that can quantify the advantage of a particular drug over another and communicate how that advantage actually translates to patient share potential. Below, we examine the specific instances where PMR comes up short and explain the approaches we take at Equinox Group to overcome these deficiencies.

1.      Primary market research is not dynamic

Given that PMR consists of semi-quantitative interviews, much of the content of these interviews is only applicable so long as important details such as the treatment paradigm, current clinical data, and competitive pipeline remain unchanged. For example, if new post-approval data that come out show a drug to be a much greater improvement over the standard of care than previously thought, such as in the case of Kisqali in HER2-, HR+ 1st line breast cancer, any PMR done involving the current treatment paradigm and efficacy in this population prior to the new data being read out would immediately become outdated and of little use to development teams. So, if a company wants new insights into the potential of their drug in the market, they have no choice but to commit more time and money to additional PMR.

At Equinox Group, we handle this problem by creating dynamic, data-driven models that can instantly deliver new outputs with a few clicks of a button. Any clinical data, launch date, competitor, or price of an agent can be updated in our models as soon as that new information is available, resulting in a new patient share prediction for your agent.

Consider the Kisqali example. At launch, Kisqali showed a mere 0.5% improvement over Ibrance — barely enough to move the needle — and initial sales reflected that.

Figure 1: Kisqali at launch

However, years later Ibrance was found to have disappointing survival data, proving it to have been far less efficacious than previously thought. A slight improvement in efficacy for Kisqali was also shown over this period. As a result, Kisqali actually proved to be far superior to Ibrance and that was reflected in the patient share that it ended up receiving.

Figure 2: Kisqali update

In our model, this shift was captured instantaneously by updating a handful of numbers — a process that took seconds, not months at no additional cost.

2. Primary market research is not unbiased empirical data

As noted above, PMR is effective in obtaining insights from physicians regarding a variety of topics. However, these insights remain opinions — capable of being influenced by personal biases — and do not reach the level of objectivity of empirical clinical evidence. This is especially true in longer interviews, where respondents become fatigued and the quality of their answers deteriorates. Framing effects compound this problem: the way an interview is structured can meaningfully shift the responses given. While exercises such as conjoint analysis can yield a rough estimate of how one additional month of mPFS or a cleaner side effect profile affects commercial success, this method is not optimal.

As a core principle, the qualitative should only be used to predict the qualitative, while the quantitative should predict the quantitative. Results from PMR can suggest whether a drug will obtain “significant” share and dominate the market, but they cannot reliably pinpoint what that share would be.

By looking at historical drug launches and quantifying the effect of the clinical innovation of a drug on its patient share potential, we have a way of discovering the impact of these factors on commercial outcomes strictly based on peer-reviewed clinical data without the need for any guesswork or opinion.

3. Preference share ≠ patient share

While the outcomes of conjoint analyses are not without their uses, at times they are misinterpreted. Perhaps the most important of these outcomes is preference share – an estimate of the percent of physician’s that would choose a given TPP among the profiles of all relevant drugs in the market. Assuming that the interviews are conducted in a way that minimizes bias, the insights gained regarding the relative strengths of TPPs are actually of great value. However, they cannot be used as a proxy for patient share. This is in large part due to the fact that these interviews are incapable of capturing the intricate market dynamics that contribute to a drug’s share. Furthermore, the TPPs that are being assessed lack the necessary detail and often do not consider important factors such as order of entry or price. Therefore, just because we can obtain an estimate for what percent of prescribers favor TPP A over TPP B, it does not necessarily mean that we can know what share either of these agents will obtain. It is also important to note that the subjects of these interviews are, at times, not a nationally representative sample of prescribers.

We avoid these issues by deriving our patient share projections from a consistent, analytical framework that weights clinical innovation (which includes price), order of entry, and competitive environment according to the results of our extensive work with historical drug launches.

4. Primary market research is expensive and labor intensive

Finally, PMR projects often take months and impose large costs upon biopharmaceutical companies. As mentioned above, these costs may compound as new information makes additional research necessary.

In comparison, Equinox Group’s models can be completed in as little as 6 weeks and include two years of after-sales service from the project start date. Because our models are driven by published clinical data rather than primary fieldwork, they can be updated in real time by the client as new information becomes available — without incurring additional research costs every time the market shifts.

If you’d like to see more about this framework, we’d be glad to walk you through a live example. Feel free to schedule a meeting.

Since 1995, Equinox Group has provided analytics to support R&D decisions at biopharmaceutical firms, assessing the potential of drugs from discovery to launch, and anywhere in between. Equinox Group specializes in predicting the commercial performance of drug programs in all stages of research and development, delivering quantitative insights regarding:

• Disease Area Strategy

• Business Development Decisions

• Market Access

• Patient Share Forecasting

• Epidemiology and Patient Flow

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.