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How can companies determine where to focus as they develop their pipelines and determine new growth opportunities? Kx Advisors’ 2020 Hot Indications List can help. In our 6th annual analysis of global R&D investment, our experts identified the top indications for industry focus.

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Author: Jenna Riffell, PhD

Managing Partner

Women’s Health: The Opportunity in Gynecology and Beyond

Posted on by Jenna Riffell, PhD

Women’s Health: The Opportunity in Gynecology and Beyond

Women’s healthcare and FemTech are garnering increasing attention, yet unmet need remains high, leaving opportunity for investment in an area with significant white space for growth. In this article, we highlight why investment in women’s health is important, where funding gaps lie, and demonstrate the potential for growth if these markets receive sufficient research and development (R&D).

An Underfunded Area in Healthcare

Women comprise half of the population worldwide, yet the women’s health space, which Kx defines as diseases only or disproportionately affecting women, has been consistently underfunded and often disregarded.

In 2021, excluding oncology, only 2% of treatments in the development pipeline were for women’s health conditions. In the US, a recent study analyzing National Institutes of Health (NIH) funding found that 93% of diseases underfunded by the NIH disproportionately affect women, while 58% of overfunded diseases are male-dominant.1 Lack of scientific knowledge of women’s health conditions can then make companies reluctant to develop treatments, a risky venture even when knowledge of the disease is advanced.2,3

Case Study: Endometriosis

Endometriosis occurs in 10% of women between the ages of 15-45,4 typified by tissue similar to the uterine lining growing outside of the uterus. The resulting pain significantly decreases patients’ quality of life, negatively impacting their performance at work, personal relationships, and mental health. Diagnosis is challenging, due to low awareness of the disease and the need for a laparoscopy to make a definitive diagnosis, leaving many patients without appropriate treatment. On average, a patient with endometriosis incurs $10,000 more direct healthcare costs annually than those without, from inpatient, outpatient, and surgical treatment alongside prescription costs. Over-the-counter (OTC) pain relief medications costs are added to these fees. Furthermore, endometriosis costs the US economy over $2,000 more than the average worker in annual absence and short-term disability costs.5 Current treatment options remain limited to painkillers, laparoscopic removal of lesions, and hormonal therapies. For those contraindicated or unresponsive to these treatments, a hysterectomy remains the only option.

Currently, the most effective pharmacotherapies are Gonadotropin Releasing Hormone (GnRH) analogs, such as elagolix (Orilissa) and relugolix (Myfembree, in combination with estradiol and norethindrone acetate), which work by inducing quasi-menopause. However, side effects including bone mineral density loss, depression, and severe nausea can be detrimental to a woman’s long-term health, and have led the FDA to restrict the duration an individual can stay on the treatment to just two years.

The current pipeline looks similarly bleak. Kissie’s Linzagolix, the only treatment in Phase III, has the same GnHR mechanism of action but with greater levels of bone mineral loss compared to approved medications. Although Phase II therapies show more promise, the market remains wide open and given the high prevalence and unmet need in endometriosis, the successful development of a safe drug would likely garner high reward.

It is not just gynecological women’s health conditions that have failed to garner sufficient R&D investment to develop effective treatments. For example, Irritable Bowel Syndrome (IBS) is a chronic disease with significant patient burden with a high prevalence in women (14%), who comprise two-thirds of all IBS patients.6 Symptoms, which include diarrhea, constipation, and bloating, can substantially impact everyday life. Inadequate treatments only targeting symptoms and low market development have left unmet need high.

There are multiple women’s health conditions ripe for development; collectively, the opportunity is vast. In endometriosis alone, a safe treatment displacing GnRHs could see peak sales of up to $3.9bn in the US.7-13

The Case for Investment

Some women’s health diseases that have already seen major market development offer an insight into the high potential patient value that can be unlocked with R&D and commercial investment.

Chronic migraine is one such example. Affecting 1 in 5 women vs 1 in 16 men, it is the leading cause of disability amongst young women.14 In 2009, the market was small, with US sales totaling $1.1bn.15 Treatment options were predominantly limited to triptans, an abortive class of medication that treats individual migraine episodes as and when they occur.16 Though effective, they are not preventative and are not suitable for those who suffer from more frequent episodes due to the risk of medication-overuse headaches (MOH), also known as analgesic rebound headaches.17

However, the market has since experienced explosive growth propelled by two treatment developments: the approval of AbbVie’s Botox in 2010 and, in 2018, the arrival of three calcitonin gene-related peptide (CGRP) antagonist mAbs; Aimovig (erenumab), Ajovy (freanezumab), and Emgality (galcanezumab). Both novel classes of treatment gave prescribers the tools to move away from treating the symptoms of chronic migraine, and towards preventing future episodes.

These landmark changes in the treatment paradigm resulted in a 200% increase in annual US sales in the last four years, from 2018 to 2022.15 Since 2020, newer oral CGRPs have been approved, further reducing patient burden in migraine. With these and further developments, the market is expected to continue to grow exponentially, with total annual US sales predicted to reach >$9bn by 2028.15

The high ROI within chronic migraine shows how a shift from reactively treating symptoms, as in endometriosis and IBS, to developing well-tolerated treatments targeting the underlying cause of women’s health diseases is both desperately needed and a significant upside opportunity. Multiple relatively untapped markets offer just such opportunity on this scale.

19-30

Polycystic ovary syndrome (PCOS), a largely understudied disease that causes metabolic issues, is one example. There are no approved treatment options despite its high prevalence, significant impact on quality of life due to hirsutism, sub-fertility, and increased risk of comorbidities such as type 2 diabetes. The generics used such as combined oral contraceptives and metformin, although effective at inducing ovulation, have little impact on metabolic issues and have tolerability concerns. The development pipeline is also particularly bleak and offers limited potential to address the high unmet need.

In irritable bowel syndrome (IBS), as discussed earlier, unmet need is high with over half of patients dissatisfied with their treatment due to side effects and inadequate efficacy,18 though there are seven marketed treatments. Pipeline development is sluggish with only two drugs currently in Phase III and nine in Phase II. This slow development can largely be attributed to poor knowledge of disease pathogenesis, linked to chronic underfunding.

Conclusion

It is evident there is extensive opportunity and necessity for development in multiple women’s health conditions. Not only are these diseases often chronic and highly prevalent, but they can significantly impact patients’ long-term health outcomes and quality of life, both key for pricing potential and market access.

Unlocking the opportunity in women’s health will require development beyond R&D. To truly address high unmet need and maximize the market opportunity, pharma companies and investors should adopt a three-pronged approach:

  • Increasing awareness of women’s health diseases is vital. In endometriosis, for example, the average delay from symptom onset to diagnosis is 8 years, while 70% of patients with PCOS remain undiagnosed in primary care. Poor PCP awareness leads to misdiagnosis, slow referrals, and a prolonged impact on quality of life.
  • Improving diagnostic tools is crucial to unlocking the full patient population. Endometriosis can only be confirmed with a laparoscopy, which is both invasive and expensive to healthcare systems, and for PCOS there is no single diagnostic test, making diagnosis challenging given the wide range of presenting symptoms. Developing diagnostic biomarkers in IBS could enable treatments to target the cause rather than symptoms, drastically improving patient outcomes.
  • Targeting investment towards effective, safe therapies that go beyond treating symptoms is key to changing outcomes. Painkillers such as non-steroidal anti-inflammatory drugs (NSAIDs) or hormonal contraceptives are heavily relied upon, particularly in gynecological women’s conditions. However, not only are women trying to conceive unable to use hormonal contraceptives, but side effects such as headaches or nausea can be unpleasant or even life-threatening in the rare case of blood clots, leading to poor compliance rates.

How Kx can help harness the opportunity in Women’s Health

The experts at Kx Advisors help evaluate opportunities, develop strategy, prioritize pipelines, and bring new treatments in Women’s Health to market. Our unique approach combines real-world experience with qualitative and quantitative data to provide unique solutions supporting our clients’ strategic growth initiatives. To learn more about how Kx Advisors can support your goals in Women’s Health, contact Jenna Riffell at jenna.riffell@kxadvisors.com.

 

Contact Our Team Today

 

References

  1. Mirin AA. Gender disparity in the funding of diseases by the U.S. National Institutes of Health. Journal of Women’s Health. 2021;30(7):956-963. doi:10.1089/jwh.2020.8682
  2. Stengel G. Female Founders Are Energizing Investment in Women’s Healthcare: Expect More In 2023. Forbes. January 2023. https://www.forbes.com/sites/geristengel/2023/01/04/female-founders-are-energizing-investment-in-womens-healthcare-expect-more-in-2023. Accessed February 20, 2023.
  3. Norris J, Bousleiman R, Scolamieri A, Atsavapranee B. Healthcare Investments and exits report annual 2022. Healthcare Investments and Exits. https://www.svb.com/trends-insights/reports/healthcare-investments-and-exits?utm_source=svb&utm_medium=pr&utm_campaign=gb-2023-01-aw-tl-ag-na-lh-na&utm_content=1pr_pct_oc_na_di_na_lp_pr. Published January 2023. Accessed February 21, 2023.
  4. Endometriosis. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/endometriosis#:~:text=Endometriosis%20is%20a%20disease%20where,and%20girls%20globally%20(2). Published March 31, 2021. Accessed February 21, 2023.
  5. Soliman AH, Surrey E, Bonafede M, Nelson JK, Castelli-Haley J. Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States. Advances in Therapy. http://doi.org/10.1007/s12325-018-0667-3. Published February 15, 2018. Accessed February 24, 2023
  6. International Foundation for Gastrointestinal Disorders. IBS Facts and Statistics. About IBS. https://aboutibs.org/what-is-ibs/facts-about-ibs/#:~:text=IBS%20affects%20between%2025%20and,3%20IBS%20sufferers%20are%20male. Published April 29, 2022. Accessed March 3, 2023.
  7. Worldometer. United States population (live). Worldometer. https://www.worldometers.info/world-population/us-population/. Published February 21, 2023. Accessed February 21, 2023.
  8. Wold Bank. Population, female (% of total population) – United States. https://data.worldbank.org/indicator/SP.POP.TOTL.FE.ZS?locations=US. Published January 1, 2021. Accessed February 21, 2023.
  9. World Bank. Population ages 15-64 (% of total population). https://data.worldbank.org/indicator/SP.POP.1564.TO.ZS. Published January 1, 2021. Accessed February 21, 2023.
  10. Shafrir AL, Farland LV, Shah DK, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Practice & Research Clinical Obstetrics & Gynaecology. 2018;51:1-15. doi:10.1016/j.bpobgyn.2018.06.001
  11. Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. Journal of Assisted Reproduction and Genetics. 2010;27(8):441-447. doi:10.1007/s10815-010-9436-1
  12. Bontempo AC, Mikesell L. Patient perceptions of misdiagnosis of endometriosis: Results from an online national survey. Diagnosis. 2020;7(2):97-106. doi:10.1515/dx-2019-0020
  13. Becker CM, Gattrell WT, Gude K, Singh SS. Reevaluating response and failure of medical treatment of endometriosis: A systematic review. Fertility and Sterility. 2017;108(1):125-136. doi:10.1016/j.fertnstert.2017.05.004 ages 15-64 (% of total population). https://data.worldbank.org/indicator/SP.POP.1564.TO.ZS. Published January 1, 2021. Accessed February 21, 2023
  14. Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z. Migraine remains second among the world’s causes of disability, and first among young women: Findings from GBD2019. The Journal of Headache and Pain. 2020;21(1). doi:10.1186/s10194-020-01208-0
  15. Evaluate Pharma. Migraine: Indication Overview. Evaluate Pharma. https://app.evaluate.com/ux/WebReport/tabbedsummarypage.aspx?itemId=631&lType=modData&compId=1019&tabId=. Published February 15, 2023. Accessed February 21, 2023.
  16. Cameron C, Kelly S, Hsieh SC, et al. Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis. Headache. 2015;55 Suppl 4:221-235. doi:10.1111/head.12601
  17. De Felice M, Ossipov MH, Wang R, et al. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann Neurol. 2010;67(3):325-337. doi:10.1002/ana.21897
  18. The Lancet Gastroenterology & Hepatology. Unmet needs of patients with irritable bowel syndrome. The Lancet Gastroenterology & Hepatology. 2018;3(9):587. doi:10.1016/s2468-1253(18)30236-x
  19. Alzheimer’s Therapeutics Market Size Report, 2022-2030. https://www.grandviewresearch.com/industry-analysis/alzheimers-therapeutics-market. Published July 2022. Accessed March 3, 2023.
  20. Acumen Research and Consulting. Irritable bowel syndrome treatment market size. https://www.globenewswire.com/en/news-release/2022/10/03/2526998/0/en/Irritable-Bowel-Syndrome-Treatment-Market-Size-is-expected-to-reach-at-USD-4-7-Billion-by-2030-registering-a-CAGR-of-9-5-Owing-to-Increasing-Incidences-of-Gastrointestinal-Disorder.html. Published October 3, 2022. Accessed March 3, 2023.
  21. DataM Intelligence. Uterine Fibroids Treatment Market. DataMIntelligence. https://www.datamintelligence.com/research-report/uterine-fibroids-treatment-market. Published June 6, 2022. Accessed March 3, 2023.
  22. Facts & Factors. Global demand of rheumatoid arthritis drugs market size & share to grow at a CAGR of 1.75%, expected to hit USD 70.1 billion mark by 2030 | rheumatoid arthritis drugs industry trends, Analysis & Forecast Report by FNF. Yahoo! Finance. https://finance.yahoo.com/news/global-demand-rheumatoid-arthritis-drugs-160000928.html#:~:text=In%20terms%20of%20revenue%2C%20the,growing%20cases%20of%20rheumatoid%20arthritis. Published February 2023. Accessed March 3, 2023.
  23. Global Data. Migraine drug market size, share & trends analysis and forecast by strategic competitor assessment, market characterization, unmet needs, clinical trial mapping and implications 2020 – 2030. Market Research Reports & Consulting | GlobalData UK Ltd. https://www.globaldata.com/store/report/migraine-market-analysis/. Published February 8, 2022. Accessed March 3, 2023.
  24. Grand View Research. Endometriosis treatment market size & trends report, 2030. Endometriosis Treatment Market Size & Trends Report, 2030. https://www.grandviewresearch.com/industry-analysis/endometriosis-treatment-market-report#:~:text=The%20global%20endometriosis%20treatment%20market%20size%20was%20estimated%20at%20USD,USD%201%2C328.89%20million%20in%202023. Published November 2022. Accessed March 3, 2023.
  25. Mordor Intelligence. Urinary tract infection therapeutics market analysis – industry report – trends, Size & Share. Urinary Tract Infection Therapeutics Market Analysis – Industry Report – Trends, Size & Share. https://www.mordorintelligence.com/industry-reports/urinary-tract-infection-therapeutics-market#:~:text=The%20urinary%20tract%20infection%20therapeutics%20market%20was%20valued%20at%20USD,the%20forecast%20period%202022%2D2027. Accessed March 3, 2023.
  26. Persistence Market Research. Polycystic ovary syndrome (PCOS) treatment market revenue to close value of US$ 6.31 bn with CAGR of 4.7% by 2032- persistence market research. GlobeNewswire News Room. https://www.globenewswire.com/en/news-release/2022/10/27/2542922/0/en/Polycystic-Ovary-Syndrome-PCOS-Treatment-Market-Revenue-to-close-Value-of-US-6-31-Bn-with-CAGR-of-4-7-by-2032-Persistence-Market-Research.html. Published October 27, 2022. Accessed March 3, 2023.
  27. Alzheimer’s Association. Why does alzheimer’s disease affect more women than men? new alzheimer’s association grant will help. Alzheimer’s Disease and Dementia. https://www.alz.org/blog/alz/february_2016/why_does_alzheimer_s_disease_affect_more_women_tha. Accessed March 3, 2023.
  28. American College of Rheumatology. Rheumatoid arthritis . https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis. Published December 2021. Accessed March 3, 2023.
  29. Buck Louis GM, Hediger ML, Peterson CM, et al. Incidence of endometriosis by study population and Diagnostic Method: The endo study. Fertility and Sterility. 2011;96(2):360-365. doi:10.1016/j.fertnstert.2011.05.087
  30. Butler CC, Hawking MKD, Quigley A, McNulty CAM. Incidence, severity, help seeking, and management of uncomplicated urinary tract infection: A population-based survey. British Journal of General Practice. 2015;65(639). doi:10.3399/bjgp15x686965

5 Misconceptions for MedTech Market Access Strategy

Posted on by Jenna Riffell, PhD

5 Misconceptions for MedTech Market Access Strategy

Market access in MedTech is a complex and rapidly evolving environment, with increasingly intense scrutiny on the costs and benefits of new technologies as the pressure on budgets increases globally. The ability to prepare for and navigate market access strategy is, now more than ever, crucial to the success of a new product, and is frequently assessed by potential partners and acquirers with the same priority as the scientific rationale or potential for favourable regulatory approval.

During the recent MedFit 2022 event in Grenoble, we discussed the most common pitfalls that may affect market access planning and strategy with leading European experts and start-up companies. Here are the top five misconceptions for market access strategy we identified.

“We want to get the approval first, then we will plan for market access”

Engagement with payers early in product development is essential. Companies should define a path to reimbursement, and understand how payers will assess their product, as early as the concept stage to use payers’ feedback to shape the technology into a marketable product and create patient and company value. Leaving engagement with payers until late in development, or after approval, can often lead companies to:

  • overlook crucial requirements
  • mistarget patient populations
  • fail to expectations to gain market access
  • fail to gain critical pricing insights to size the commercial potential

Missing the opportunity to treat payers as your sounding board can cause delays and significant restrictions in access, while timely and iterative payer engagement has the potential to speed up the development process.

“The evidence we are generating for regulators will be sufficient for our market access strategy”

Regulatory decisions are at the top of priority lists for MedTech entrepreneurs both in the US and Europe. Selection of the right pathway and preparation of required submission dossiers are time-consuming and costly and constitute a necessary condition for market access. Late-stage start-ups agree, nonetheless, that it is far from sufficient, and payers themselves corroborate this perspective. In a recent Kx Advisors study, 100% of interviewed executives for major US payers agreed going beyond the evidence required for regulatory approval is key for market access strategy. Payers increasingly require demonstration of patient value not only with differentiated clinical efficacy and safety but through increased compliance and improved patient outcomes and satisfaction. They are also seeking additional sources of data, such as real-world evidence, insurance claims, and adverse event reports. MedTech companies should plan and pre-empt these requirements by carefully designing their studies for a payer-targeted set of endpoints as early as possible and generating evidence with not only regulators but also payers in mind.

“There is an established price for devices like ours”

Existing pricing and reimbursement benchmarks provide valuable insights for market access strategy, as showing cost-effectiveness in comparison to the current standard of care is an important part of any MedTech company’s economic narrative. However, payers’ focus is shifting towards a more holistic view, with greater interest in:

  • improved patient outcomes
  • demonstrated longer-term value
  • ease of use
  • adherence to treatment
  • patient satisfaction

Four out of every five payers recently interviewed by Kx Advisors indicated a preference for increased value over purely lower cost of treatment and were ready to assess pricing based on a complete view of benefit for the patient and healthcare system. The approach MedTech companies take to frame, measure, and present this value becomes a tactical choice, and a key element of a broader commercialisation strategy, that should not be dismissed or made based on a simple competitive analysis.

“We will focus on a market we know and aim for broad market access”

Many MedTech companies decide to first target their home geographic market, building on their familiarity with it, knowledge of the local language and system, and network of contacts. This approach, while easier from a product development perspective, may not allow companies to fully capture their commercial potential. In conversations with Kx Advisors, start-ups with prior product launch experience highlighted the need for fast market deployment and the value of testing the product with first adopters (and getting the product paid for early on) typically outweighs the breadth of market access. The choice of the first markets in which to launch is a strategic decision, and market access becomes one of the key drivers that should be considered in careful prioritisation of the highest potential markets. Entrepreneurs should be aware of both regional (e.g., US vs EU) and intrinsic (e.g., openness to innovative technologies) differences among payers, as well as differing patient population structures and accessibility, and explore avenues that expedite first market access, such as targeting research institutions or venturing into new geographies.

“Payers are not willing to consider innovative reimbursement models”

Getting paid for innovative technologies is notoriously difficult, especially when there is no easy way to make them fit within the established market access pathways for medical devices. The emergence of digital therapies and connected health, as well as the ongoing shift towards at-home therapies accelerated by the COVID pandemic, have only made the landscape more complex. At the same time, the awareness and urgency to address these challenges is on the rise among payers. Approximately 60% of payers recently interviewed by Kx Advisors stated they are exploring value-based reimbursement options and new, alternative pricing models for medical technologies (e.g., subscriptions or device-as-a-service arrangements) will be an increasingly welcome element of future coverage decisions. Building a differentiated market access strategy that accounts for multiple possible business models and reimbursement scenarios and exploring those early with key stakeholders can allow MedTech companies to create and leverage these opportunities.

 

Has your commercialisation strategy ever been impacted by any of these common misconceptions? Or are you currently facing other strategic decisions that will be crucial for your MedTech company’s growth? Feel free to contact Kx Advisors for a follow-up discussion.

Contact Our Team Today

 

Jenna Riffell is a Managing Partner at Kx Advisors, based in London.

Przemek Czerklewicz is a Principal at Kx Advisors, based in London. During the recent MedFit Event 2022 he led an expert panel titled “Innovators’ checklist for market access”.

 

 

Rare Disease Drug Development & Commercialization Learnings, Opportunities & Debates at World Orphan Drug Congress USA 2022

Posted on by Jenna Riffell, PhD

The Kx team attended the World Orphan Drug Congress (WODC) in Boston, MA last week and came away energized from three days of sharing ideas, inspirational stories, and panel discussions. This event brings together the full range of stakeholders who drive and support orphan drug development, regulatory approval, treatment delivery, and patient/caregiver support services. Here we discuss a few themes we heard across meetings and presentations:

Capturing the full market potential for a new orphan drug is a challenge; diagnosis and treatment gaps add to the unmet needs a new treatment needs to address

Repeatedly, newly approved treatments for rare diseases with a strong clinical profile (i.e., safe and effective) have not achieved the degree of adoption forecasted pre-launch. Why? With humility, drug developers acknowledged their own shortcomings in not building a comprehensive ecosystem of care for target patients, their caregivers, HCPs, and payers.

Unfortunately, there is no universal go-to-market (GTM) playbook for launching a treatment in an orphan indication; however, key questions to ask when GTM planning in rare diseases in have become clear:

  • What is the daily reality and emotional state of patients and caregivers?
  • What breakpoints exist in the patient journey, and how can we address those?
  • How can barriers to delivery be mitigated through just-in-time delivery infrastructure and treatment sites creation for gene therapies?
  • How should value be measured (to ensure access and coverage continuation)?

The term “beyond the pill” is still a popular idea, but there is a need to define what that means for meeting the needs of different patient, HCP, and payer populations. By establishing trusting, longitudinal relationships with the patients, caregivers, and HCPs they strive to serve, drug developers are successfully building tailored, comprehensive GTM strategies today for the next wave of orphan drug launches, building the foundation for “beyond the pill” to be more than a catchphrase. 

Value differentiation is best achieved through focus on simple, straightforward clinical endpoints

For over a decade, rare disease treatments have seen greater flexibility from regulators on primary endpoint designations than treatments for more prevalent indications; however, we consistently heard that leniency in clinical trial design may fade. Until now, drug developers could drive endpoints selection based on early trial results and carry these through to regulatory approval reviews. As noted by Simone Boselli, Public Affairs Director, EURODIS, during one of the panel discussions, too often today these endpoints are abandoned post-approval given challenges with continued tracking in real-world settings.

Going forward, drug developers should pursue greater prospective consideration and engagement to ascertain how regulatory bodies (FDA, EMA, health technology assessment (HTA) bodies) expect data packages to be constructed. Emphasis will be placed on using clinical endpoints that are simple to compare across studies by competing developers and straightforward to extrapolate to functional benefits for patients, as well as feasible to continue to measure in the real world as drug developers aim to build a real-world evidence base. In the future, drug developers presenting unique (rather than universally accepted) clinical endpoints may run into delays or rejections, costing time, revenue, and patient access to novel treatments.

Rare disease patients desire true partnership, including greater influence over the risk tolerance decisions and transparency on drug development setbacks

Appropriately, keynote presentation sessions often included patient advocates such as Allyson Berent, COO, GeneTx*, who shared her experience from her daughter’s Angelman Syndrome (AS) diagnosis at 6 months old. When she realized there were no approved treatments for the condition, she dedicated her time and energy to pursuing an effective treatment, ultimately becoming the Chief Science Officer of Foundation for Angelman Syndrome and co-founder of GeneTx.

(*note: GeneTx was acquired by Ultragenyx on 7/19/22)

We at Kx Advisors applaud the dedication of individuals, such as Allyson Berent, who work relentlessly to bring innovative therapies to patients. Also, we are telling her story here because her asks to industry were echoed by others at WODC:

  • Further elevate patients’ voices and requests – creating an ecosystem of care requires early and frequent patient input 
  • Consider that the risk-reward tolerance when patients are desperate for a lifeline may be different than industry’s view; many felt patients should have more influence on the calculus 
  • Increase transparency of critical feedback from the FDA to drug developers when reviewing clinical results, as patients are central to progress and deserve transparency on both advancements and setbacks; this sharing rarely occurs today, and collectively holds back innovation for the sake of competitive advantage

 

How Kx Can Help

Do you want to discuss further our takeaways from the World Orphan Drug Conference? Does your organization need to address specific challenges in rare disease asset planning and launch strategy? If so, please contact Brett Larson brett.larson@kxadvisors.com or Jenna Riffell at jenna.riffell@kxadvisors.com.

Contact Our Team Today

Why Your Orphan Drug Needs A Global Market Access Strategy

Posted on by Jenna Riffell, PhD

Why Your Orphan Drug Needs A Global Market Access Strategy

Key Takeaways

  • An effective global market access strategy for rare diseases requires a higher degree of regional customization compared to other launch prep activities
  • While regulatory approval in first-tier US and EU markets can often translate on a global scale, as many local regulatory bodies look to FDA or EMA approval as the gold standard, local market access requirements vary significantly
  • This variation includes, among other factors:
    • Price referencing
    • Health technology assessments
    • Public vs. private payer dynamics
    • Rebates and discounts
    • Reimbursement restrictions (e.g., step-through requirements)
    • Real-world-evidence-based payment models
  • Companies must be ready to develop individual market strategies to address these country-specific challenges

Why You Need A Global Market Access Strategy

Each country poses unique challenges in developing a rare disease market access strategy. While some areas face a scattered patient population, others may face challenges such as immature physician and patient advocacy networks. Additionally, the high cost of certain drugs, like gene therapies, are handled differently by different countries. These nuances in market behaviors and structure underlie the importance of looking across the global landscape when developing a market access strategy. For US-based pharma companies, developing a comprehensive market access plan, rather than simply pivoting off a US-focused market access strategy, will ensure the long-term launch plan meets global needs and is positioned for success.

World Map Showing Why Companies Need Global Strategy

Click to expand

How To Develop A Global Market Strategy

Rare disease companies need to answer complex key questions:

  1. Which markets will be targeted for launch?
  2. How much compromise in pricing is possible to gain access in global markets, particularly given reference pricing?
  3. What evidence is available or will be developed to support global market access?­

The first step in entering a market is to identify which markets offer a path to reimbursement with sufficient pricing potential. The next step is assessing your pricing flexibility, as offering a lower price than in the US or even the EU5 can increase the likelihood of reimbursement in key OUS markets. When making these assessments, identifying patient access schemes, such as named patient supply (NPS), can validate and drive demand. Once an orphan drug gains regulatory approval, companies must be prepared to work with stakeholders, such as patient advocacy groups and KOLs, to demonstrate need for the orphan drug, clinical and cost effectiveness, and drive favorable reimbursement decisions. These stakeholders are pivotal in some markets, ensuring that patients can get treatments at affordable costs throughout the duration of their treatment. As an example, in Brazil, patient advocacy groups work closely with patients to navigate court systems that enable patients to make a legislative case for drug access and coverage before national approval, including for orphan drugs (see more below). 

Rare Disease Brazil Case Study

Click to expand

External Reference Pricing

External reference pricing adds significant complexity to global market access strategy as the application of referencing varies greatly among countries, including:

  • Product Applicability: categories of products for which referencing is applied, including referencing only for drugs in a specific care setting (e.g., inpatient hospital), innovative medicines for which there is no alternative available on the market, or high-cost medicines
  • Basket Composition: both the total number and specific countries selected to include in the reference basket (typically selected based on comparable GDP per capita)
  • Calculation Method: use of either an average price or selection of the lowest price of basket countries
  • Decision Process: whether used as the main systematic criterion (most common) or as supportive information only when setting a drug price
  • Re-evaluation: pricing must be re-evaluated frequently after initial price is set

In Europe, the vast majority of countries use some form of reference pricing. With reference pricing, there is increased pricing interdependence between countries. Given the high prices of orphan drugs, it is critical for rare disease companies to develop a launch sequencing strategy that factors in price referencing. This could include strategically launching first in high-priced countries without reference pricing, then focusing on lower-priced countries.

Real-World Evidence

RWE is gaining momentum globally as real-world data (RWD) sources become available—specifically electronic health records and claims data that provide a basis for evaluating outcomes. New treatment costs remain high for rare diseases, putting pressure on pharma and biotech companies to demonstrate results for premium pricing with payers. Gene therapies are especially costly due to their complexity, making RWE an ideal tool. A prime example is the AveXis-Novartis approach to payer contracting with Zolgensma, a one-time gene therapy treatment that replaces lifetime chronic therapy for patients with spinal muscular atrophy Type 1, and which launched in the US in June 2019. Gene therapies are breaking pricing norms since manufacturers are only able to generate revenue from “one-shot” treatment for each patient, and Zolgensma made waves with a US price point of $2.1M per patient—the most expensive treatment on the market as of this writing. Novartis worked with payers to establish efficacy-based reimbursement and a 5-year installment payment option to spread payment for treatment over time. With these arrangements, risk is lower for payers, who can pay $425K annually for five years and better justify a patient switch from Biogen’s Spinraza, a chronic treatment estimated to cost $4M+ over a 10-year period. Zolgensma won coverage for 90% of US commercial patients within its first full quarter on the market, with all payers taking advantage of value-based contracting; however, initial uptake of the installment-based payment system was limited.  

Similarly, in May of this year, Zolgensma received conditional approval in Europe with the “Day One” access program, which ensures the cost of patients treated before national pricing and reimbursement agreements are in place aligns with the value-based prices negotiated following clinical and economic assessments. Working within the existing pricing and local reimbursement frameworks, the “Day One” access program for EU governments and reimbursement agencies allows the company to tackle entry into markets faster and with more flexibility. This system sets up a win for each stakeholder: the patient, the health and reimbursement bodies, and AveXis-Novartis. With the Temporary Authorization for Use (ATU) program, it became immediately accessible in France and should be available in Germany shortly. 

Coverage for therapies like Zolgensma remains dependent on demonstrating values, so companies must leverage proof of value when looking to capture new patient markets. RWE and patient-reported outcomes (PROs) provide stakeholders with concrete data to inform formulary addition and clinical trial outcome endpoints.

Case Study USA

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Moving Forward

An effective global market access strategy for orphan drugs must be adaptable to different regions and their unique challenges to be effective. As companies work through the key questions outlined above to create a successful global market access strategy, tools like RWE and external reference pricing can support tackling a large range of location-specific issues.

How Kx Can Help

Our experts evaluate business opportunities, deliver top-notch expertise, and make data-driven recommendations to our healthcare clients. Kx Advisors can guide your organization through the process of developing and implementing a global market access strategy for your rare disease drug.

Contact Our Team Today

Sources

https://www.pacificbridgemedical.com/wp-content/uploads/2014/03/Orphan-Drugs-in-Asia-2017.pdf

http://info.evaluategroup.com/rs/evaluatepharmaltd/images/2014OD.pdf

https://www.europeanpharmaceuticalreview.com/article/62846/orphan-drugs-regulation-eu/

https://ec.europa.eu/health/sites/health/files/files/committee/stamp/2015-05_stamp2/5.pdf

https://www.eurordis.org/training-health-technology-assessment

https://www.rtihs.org/sites/default/files/Rare%20Disease%20Webinar%20Slides_Final%20Feb%2027.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802694/

https://www.biospace.com/article/releases/avexis-announces-innovative-zolgensma-gene-therapy-access-programs-for-us-payers-and-families/

https://www.fiercepharma.com/pharma/novartis-zolgensma-beats-data-woe-payer-resistance-strong-and-high-interest-ceo

https://www.globenewswire.com/news-release/2020/05/19/2035354/0/en/AveXis-receives-EC-approval-and-activates-Day-One-access-program-for-Zolgensma-the-only-gene-therapy-for-spinal-muscular-atrophy-SMA.html

https://mapbiopharma.com/home/2020/04/landmark-pay-for-performance-contract-agreed-in-germany/

Elective Procedures After COVID-19: How To Support Rebounding Demand

Posted on by Jenna Riffell, PhD

Elective Procedures After COVID-19: How To Support Rebounding Demand

Due to COVID-19, pharmaceutical and medical device organizations face unprecedented obstacles, impacting product forecasting, pipelines, and overall corporate strategy. One major business challenge created by this pandemic is the policy-driven limitation on elective procedures, resulting in restricted healthcare provider (HCP) accessibility for patients.  Approximately 27% of patients experienced an elective procedure delay or cancelation due to COVID-19, according to an April 13th poll of over 2,500 US adults.  

Defining Elective and Essential Procedures  

There is no single definition of elective procedure, and the meaning of the term varies across the globe and from person to person, given how HCPs and patients view the urgency of medical situations. Generally, an elective procedure is recognized as a non-urgent procedure that can be scheduled in advance. The term elective procedure may be associated with non-immediately life-saving procedures; however, examples of necessary elective procedures include cancer surgeries, kidney stone removal, mental health services, and joint replacements.  

The Impact of Pandemic Restrictions   

The impact on individual hospitals and the procedures they perform is dependent on their location, the severity of the pandemic there, and how different regions are managing the epidemic. While some hospitals are fully operational, others have been prioritizing COVID-19 patients and chose, or were legislated, to scale back on elective procedures.  

We are beginning to see a rebound in hospital visits and elective procedures performed in COVID-impacted areas. There is evidence that hospital visit declines in the US may have bottomed out, with a 4% increase in outpatient hospital visits in the second week of April marking the first increase in visit volume since early March. As lockdown measures are relaxed, the re-introduction of elective procedures may take some time. The pandemic has increased anxiety about seeking treatment, keeping patients from going to hospitals. Emergency room visits are down by about 50% across New York City Health and Hospital locations. This fear could take time to subside and impact patient behavior for longer than policy measures restrict procedures.  

The evolution of elective procedures will be region-dependent, as strategies to lift lockdown measures and priorities are decided at a national or regional level. As the pandemic continues and cases decrease, nations are facing the challenging decision of whether to prioritize certain elective procedures, and if so, which elective procedures to bring back first. In the United Kingdom, mental health and cancer surgeries are being prioritized amongst elective procedures. However, as we see demand rise again for specific products or procedures, this resurgence will likely result in a backlog of procedures. This backlog will have a direct impact on other procedures. For example, we may see a surge of cancer surgeries that were delayed by pandemic mitigation measures, resulting in less available operating room space and limited opportunities for other operations.  

Preparing For Procedures Now And Post-COVID-19   

With the rollback of lockdown measures and changes on the horizon for elective procedures, healthcare organizations can support HCPs and patients in new ways. There are several factors procedure-focused companies must consider as they face the pandemic’s challenges now and throughout the global recovery:  

  • Map demand and prepare for the backlog: Companies must monitor changes in government regulations, medical association guidance, and access to personal protective equipment (PPE), as well as analyze the continuing evolution of COVID-19 to determine which products can meet demand in identified places at the correct time. Part of this calculation must include a backlog in regions that begin to allow elective procedures. With this expected backlog of elective procedures, companies must ensure they are ready to support HCPs and patients to ensure a smooth ramp up.  
  • Explore new ways to aid HCPs performing procedures: Crafting specialized product protocols, creating guidance for performing specific procedures more safely, and providing PPE where appropriate can support HCPs as they adapt. HCP accessibility and increased demand could also have implications for field team deployment. While it may now be more appropriate for field teams to actively reach out to HCPs, COVID-19 safety concerns may intensify scrutiny on sales rep involvement in surgeries. Understanding the changing landscape will be key for healthcare companies during this rebound phase. 
  • Devise additional ways to help patients: With the looming fear of exposure to COVID-19 while in care settings for procedures, pharmaceutical and medical device companies can support HCPs’ new protocols to keep patients safe during procedures. From reinforcing safety of minimally invasive procedures in outpatient clinics rather than hospitals, to crafting additional guidelines for keeping medical devices uncontaminated, companies can provide value in new ways.  

How Kx Advisors Can Help   

Kx Advisors is continuing to evaluate business models, deliver top-notch expertise, and make profitable recommendations to our healthcare clients. Our team of experts can help your organization assess demand during and after COVID-19 and adapt your  corporate strategy to position you for long-term success.   

 

Contact Our Team Today

Adapting In COVID-19: A Product Forecasting Framework

Posted on by Jenna Riffell, PhD

Adapting In COVID-19: A Product Forecasting Framework

Kx’s Key Takeaways For Product and Finance Teams    

  • Separate The Trough And Rebound: Modeling both the duration of the trough and the slope of the rebound, from peak COVID-19 infections to recovery, is critical to developing an accurate product forecast    
  • Layer In Regional Segmentation: Accurate forecasting requires more regional segmentation than most models demand due to the local variation in COVID-19 cases and varied government restrictions responding to the virus  
  • Expand Data Sources: Although COVID-19 is unprecedented in many respects, historical data can be used to model its impact. Utilizing a variety of data sources—analog regions that roll back restrictions earlier, patient and provider research, and prior economic downturns —can provide a valuable frame of reference to develop a more informed forecast  
  • Make It A Living, Breathing Model: With new restrictions and the medical community’s fast-paced response, it’s critical for companies to regularly monitor and update forecasting assumptions as the pandemic evolves   

COVID-19 Impacts Product Forecasting For Pharmaceutical and Medical Device Companies  

Dealing with significant evolving obstacles associated with COVID-19, businesses worldwide are adjusting their 2020 strategic plans. Pharmaceutical and medical device companies face particularly complicated hurdles, including procedure delays, office closures, and more that prevent patient access to their products. In this time of uncertainty, it’s critical to develop an informed view of future sales to establish a strategic plan and mitigate future risks to the business.  

Your Adaptable Product Forecasting Framework  

Kx Advisors created this framework to assist organizations in accurately forecasting sales during a time of high uncertainty with COVID-19. We recommend approaching the problem in two stages: the trough and the rebound. While organizations around the globe are currently in midst of the trough, understanding both stages is crucial for full-scale recovery. The questions we’ve identified for this framework can be split into three categories of barriers that COVID-19 presents: policy barriers, behavioral barriers, and economic barriers. Policy barriers are directly related to the pandemic management decisions of governments and medical associations, while behavioral barriers are driven by changes in industry competitor, physician, and patient behavior, and economic barriers are those created by changing economic conditions affecting willingness to pay.

 

COVID-19 Product Forecasting Framework Graphic Depicting Trough and Rebound

 Click to expand

Planning During COVID-19  

While no one can predict the future, this framework should help you gain critical insights to better project and respond to these challenges. Leveraging this tool to strategize is only step one; your product team must continually monitor the quickly evolving factors impacting the framework’s components and adjust your strategy as needed to stay ahead of the economic effect of this pandemic.  

Kx Is Here To Help  

Struggling with product forecasting during this crisis? With extensive forecasting experience, we’re experts at quantifying what is hard to quantify.  Our healthcare experts will rapidly analyze the changing field and build strategies with your team around the opportunities we identify. 

 

Contact Our Team Today

How Is COVID-19 Impacting Procedure Volume?

Posted on by Jenna Riffell, PhD

Understanding The Changing Healthcare Landscape Is Key For Commercial Strategy

Treating Patients During A Crisis

The spread of COVID-19 has disrupted the healthcare industry. With hospitals scrambling to prepare for an influx of patients and government officials enacting large-scale safety measures, the overall volume of medical procedures is decreasing dramatically. The Centers for Medicare & Medicaid Services, the Centers for Disease Control and Prevention, and other healthcare thought leaders are recommending that providers limit non-essential and elective scheduled surgeries and procedures. However, not all procedures are equally impacted.

Graph depicting degree of impact on procedures based on setting and urgency

While COVID-19 is reducing treatment volume, the degree of impact varies depending on the urgency of the condition and the treatment setting. Procedure-focused companies must understand this evolving environment to forecast accurately and make crucial business decisions, such as resource deployment, commercial spending, and launch planning. Due to the fast pace of this pandemic and the corresponding response of the healthcare community, it can be difficult to predict the risks and disruptions organizations face. Without clear insight into the near-daily changes that medical professionals encounter, many companies’ strategic plans are no longer actionable.

How COVID-19 Impacts Orthopedics

The Kx team analyzed the consequences of COVID-19 for the orthopedic field, exploring trends that could inform expectations for the coming weeks and months. Our survey of orthopedic specialists across the US highlights that in most areas of the country, urgent and emergent procedures are still being performed, but elective procedures are being canceled.

US map depicting degree of impact on procedures by location

 

The only orthopedic procedures that are being performed treat truly urgent conditions: cases of infection and trauma. However, even critical treatments like these are being performed at a lower volume than before COVID-19 emerged in the US.

Graph depicting the volume by type of procedure

Lessons Learned For Other Specialties

Our case study in orthopedics serves as an opportunity for companies focused on other specialties to apply insights to their fields. With ~97% of orthopedic specialists only performing urgent procedures (if at all), healthcare professionals and companies can expect to see similar trends throughout the industry. As ~38% of orthopedic specialists are not rescheduling at this time, organizations throughout the healthcare industry must adjust their expectations and expect the repercussions of COVID-19 for an extended period.

Kx Advisors, Experts In Resilience

Is your organization impacted by the sharp decline in procedures due to COVID-19? Kx Advisors can help. Our experts offer tailored guidance in forecasting, commercial strategy, and launch planning, projecting future trends and empowering your organization to adapt during a global pandemic or another unpredictable event. Our team will continue to monitor trends over time to help predict which procedures are resuming and when, giving your organization current data to inform your key business decisions.

Contact Our Team For More Information Today

Rare Diseases – Stakeholder Education

Posted on by Jenna Riffell, PhD

The Role of Stakeholder Education in Rare Diseases

Despite the growing pipeline of orphan drugs, ~95% of rare diseases do not yet have an FDA-approved treatment. This increasing momentum in rare disease R&D has further highlighted the ever-present need for stakeholder education and engagement, which is critical to begin well before drug commercialization. Patients, key opinion leader (KOL) physicians, and other physician specialists supporting treatment are primary players in the rare disease space that influence treatment selection and access to novel therapies. Rare disease stakeholder education plays a critical role at every stage in drug development and commercialization and should be top of mind for rare disease companies regardless of whether they are designing clinical trials or preparing for product launch.

Caption: KOLs play an important role in the patient journey. From diagnosis to treatment access, KOLs support rare disease patients in making important decisions about managing their condition and obtaining the best possible care.

How to Implement Rare Disease Stakeholder Education

Rare disease companies need to engage with different stakeholders to address various pain points along the patient journey and maximize the opportunity for their orphan drug. KOL communities will be especially valuable throughout the drug development process. As a part of tight-knit medical communities, KOLs collectively influence treatment standards and typically have a deep understanding of how access to care and treatment varies across global markets. KOLs will be play important roles in:

  • Diagnosis: Timely diagnosis remains a major challenge for rare diseases; on average, patients wait close to 5 years and visit over 7 physicians before an accurate diagnosis is made. Delayed diagnosis can further complicate the patient pathway, often increasing the number of interventions required after the disease has progressed. Dedicated education efforts targeting physicians and patients, as well as improved testing access, can ensure accurate and earlier diagnoses.  Companies should look at this as an opportunity to educate stakeholders and develop genetic tests to increase diagnosis rates and maximize patient adoption. While there are currently no genetic tests available for many rare conditions, competition to develop effective diagnostic tests will increase after a disease modifying treatment is introduced to the market. KOLs can also support development of innovative screening techniques, including using artificial intelligence or predictive analytics with electronic health record data to identify patients at high risk of an undiagnosed rare disease. 
  • Drug development: KOLs play an integral role in drug development, ranging from supporting animal model design, clinical trial design, and designing clinical endpoints (e.g., novel disease severity / quality of life scales). As disease experts, KOLs understand needs, market access challenges, and adoption drivers and should be considered an asset to pre-commercialization efforts for rare disease companies. KOL in-depth expertise and knowledge should be leveraged for refining target product profiles (in particular via advisory boards), understanding treatment barriers across markets, estimating the size of local patient populations, selecting sites and recruiting patients for clinical trials, and supporting market access and reimbursement decisions for regulatory bodies and payers. Companies will greatly benefit from early and global KOL engagement throughout the drug development process – whether as consultants or scientific investigators.
  • Launch planning: KOLs are very familiar with the gaps in the existing patient pathway, and, post drug launch, can provide insights on ideal future-state diagnosis and referral patient pathways. Rare disease companies should continue to collaborate with KOLs to streamline the access pathway and demonstrate their long-term commitment to a given patient population. Post-launch trials also offer an opportunity for KOLs to disseminate information and develop stakeholder education deliverables about achieved health outcomes and / or pivotal trial results with physicians and patient advocacy groups (PAGs). Over time, KOLs become strong advocates for drugs, especially those that they have supported through development, and can be important allies as companies move towards commercialization. 

Caption: Companies looking to launch a new drug should focus on how they can work with KOLs and other stakeholders to best understand local market opportunities, including disease prevalence/incidence, frequency of diagnosis, and likelihood of treatment adoption.

Centers of Excellence (COEs) are another critical component of rare disease stakeholder education. COEs, in conjunction with KOLs and their reference networks, offer rare disease patients specialized care and expertise. COEs combine clinical research, knowledge, and treatment services to become a regional or global “hub” for undiagnosed or recently diagnosed patients. The multidisciplinary approach they take is not only valuable to patients, but also biopharma companies as they enter commercialization stages. COEs are a reliable source of support for companies, referring patients from their centers and supporting commercial activities later down the road. A strong relationship with COEs and their KOLs can mean success for rare disease companies looking to work closely with patient populations and demonstrate long term commitment.

Caption: Centers of Excellence are a critical component of the rare disease patient pathway. Patients seek diagnosis support, treatment advice, and care coordination from experts at COEs across the globe.

KOLs and COEs are key stakeholders in the rare disease space and should be top of mind for companies looking to enter the space. As competition within the market increases, how companies work with KOLs to leverage their expertise and best understand the treatment landscape will become a key differentiator. KOLs, though critical to the market, are not the only stakeholders that companies should keep an eye on. In the next part of these series, we will share why patient advocacy groups are an important ally for both patients and rare disease companies, and how they can successfully work together to introduce new treatments to the market.