Mar 14, 2023

Raajit K. Rampal, MD, PhD

Raajit K. Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center, discusses how the role of JAK inhibitors will continue to evolve in the treatment of patients with myelofibrosis.

patients with myelofibrosis, Rampal begins. However, it is not believed that JAK inhibitors modify the disease, and their effects can be limited in subgroups of patients, Rampal says.

Multiple JAK inhibitors are now available for the treatment of myelofibrosis, and this has allowed select patients to potentially be cycled between different agents, Rampal explains. As more data have emerged, they have been able to demonstrate how various JAK inhibitors can effect patients differently, and this may put clinicians in a position to better select certain JAK inhibitors for select patients, Rampal emphasizes.

Within the next 2 to 3 years, it is possible that the treatment landscape for patients with myelofibrosis will drastically shift, Rampal says. Multiple agents are in late phase 3 trials, and if data continue to prove positive for some or all of these treatments, there will be an influx of new treatment options entering clinical practice, Rampal notes.

Although the landscape will change, it remains unclear exactly how that will happen. One possible scenario is that trials for the drugs in development are successful, and then clinicians will need to determine if these treatments will be added on to current regimens for use in combinations, or if they should follow the use of JAK inhibitors if a patient does not have a full response, Rampal notes. These remain unanswered questions, but they will be addressed in short time as other agents begin to enter the treatment landscape, Rampal concludes.

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Published March 13, 2023

DelveInsight’s “Myelofibrosis Market Insights, Epidemiology, and Market Forecast-2032″ report offers an in-depth understanding of the Myelofibrosis, historical and forecasted epidemiology as well as the Myelofibrosis market trends in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan.

The Myelofibrosis market report covers emerging drugs, current treatment practices, market share of the individual therapies, and current & forecasted market size from 2019 to 2032. It also evaluates the current treatment practice/algorithm, market drivers & barriers, and unmet medical needs to curate the best of the opportunities and assess the underlying potential of the market.

Myelofibrosis Overview

Myelofibrosis (MF) is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar like material. It is classified as a type of chronic leukemia and belongs to a group of blood disorders called myeloproliferative diseases.

Some of the key facts of the Myelofibrosis Market Report: 

• The Myelofibrosis market size is anticipated to grow with a significant CAGR during the study period (2019-2032)
• In June 2022, Sierra Oncology submitted an NDA to the US FDA for momelotinib to treat myelofibrosis. The FDA has accepted the NDA and has assigned a PDUFA date of 16 June 2023
• Vonjo, approved by the US FDA on February 28, 2022, is a kinase inhibitor used for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L
• In various studies of European countries, annual prevalence of Myelofibrosis ranged from 0.5–9 cases per 100,000 individuals
• Myelofibrosis is a disease that tends to affect the middle-aged and elderly population with a mean age of 60 years at diagnosis. Males are more commonly affected than females. In younger children, girls are affected twice as often as boys
• The total prevalent population of myelofibrosis in the 7MM comprised of 39,735 cases in2021and is projected to increase during the study period (2019–2032)
• In 2021, the highest number of prevalent cases were observed in the US. The total prevalent population of myelofibrosis in the US is 19,815 in 2021 and is projected to increase during the forecast period (2022-2032)
• Key Myelofibrosis Companies: Pharmaxis, Keros Therapeutics, Bristol-Myers Squibb, Ascentage Pharma Group Inc., Sumitomo Pharma Oncology, Galecto Biotech AB, Actuate Therapeutics Inc, Karyopharm Therapeutics Inc, AbbVie, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Taiga Biotechnologies, Inc., Rigel Pharmaceuticals, Celgene, Novartis Pharmaceuticals, Sierra Oncology, Inc., Incyte Corporation, Imago BioSciences, Inc., Samus Therapeutics, Inc., Constellation Pharmaceuticals, Kartos Therapeutics, Inc., NS Pharma, Inc., Nippon Shinyaku Co., Ltd., Geron Corporation, Inc., Suzhou Zelgen Biopharmaceuticals Co.,Ltd, Hoffmann-La Roche, Lynk Pharmaceuticals Co., Ltd, Chengdu Zenitar Biomedical Technology Co., Ltd, Prelude Therapeutics, Cellenkos, Jacobio Pharmaceuticals, Active Biotech, The Menarini Group,  Cyclica Inc, GAT Therapeutics, Hinova pharmaceuticals, iOnctura,  Telios Pharma, Inc., and others
• Key Myelofibrosis Therapies: Momelotinib, Navitoclax, Parsaclisib, Reblozy, Pelabresib, PXS-5505, and others

 Key benefits of the Myelofibrosis Market report:

1. Myelofibrosis market report covers a descriptive overview and comprehensive insight of the Myelofibrosis Epidemiology and Myelofibrosis market in the 7MM (the United States, EU5 (Germany, Spain, France, Italy, UK) & Japan.)
2. The Myelofibrosis market report provides insights on the current and emerging therapies.
3. Myelofibrosis market report provides a global historical and forecasted market covering drug outreach in 7MM.
4. The Myelofibrosis market report offers an edge that will help develop business strategies by understanding trends shaping and driving the Myelofibrosis market.

Download the report to understand which factors are driving Myelofibrosis epidemiology trends @ Myelofibrosis Epidemiological Insights 

Myelofibrosis Market  

The dynamics of the Myelofibrosis market are anticipated to change in the coming years owing to the expected launch of emerging therapies and others during the forecasted period 2019-2032.

“According to the estimates, the highest market size of Myelofibrosis was found in theUnitedStates and the least was in Spain across the 7MM. Besides, the upcoming therapies of Myelofibrosis are expected to combat the current unmet needs faced by the patients with Myelofibrosis and add to the overall growth of the Myelofibrosis market size.”

 Myelofibrosis Epidemiology

The epidemiology section provides insights into the historical, current, and forecasted epidemiology trends in the seven major countries (7MM) from 2019 to 2032. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. The epidemiology section also provides a detailed analysis of the diagnosed patient pool and future trends.

Myelofibrosis Epidemiology Segmentation:

The Myelofibrosis market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into:

• Total Prevalence of Myelofibrosis
• Prevalent Cases of Myelofibrosis by severity
• Gender-specific Prevalence of Myelofibrosis
• Diagnosed Cases of Episodic and Chronic Myelofibrosis

Myelofibrosis Drugs Uptake and Pipeline Development Activities

The drugs uptake section focuses on the rate of uptake of the potential drugs recently launched in the Myelofibrosis market or expected to get launched during the study period. The analysis covers Myelofibrosis market uptake by drugs, patient uptake by therapies, and sales of each drug.

The report also covers the Myelofibrosis Pipeline Development Activities. It provides valuable insights about different therapeutic candidates in various stages and the key companies involved in developing targeted therapeutics. It also analyzes recent developments such as collaborations, acquisitions, mergers, licensing patent details, and other information for emerging therapies.

Myelofibrosis Therapies and Key Companies

• Momelotinib: Sierra Oncology
• Navitoclax: AbbVie
• Parsaclisib: Incyte
• Reblozy: Celgene/Bristol Myers Squibb
• Pelabresib: MorphoSys
• PXS-5505: Pharmaxis

Myelofibrosis Market Strengths

• Myelofibrosis is a rare form of hematologic cancer; thus, companies developing its treatment options can possess several advantages like market exclusivities, premium pricing, trial subsidy, and other benefits from the government bodies for R&D.

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Mar 8, 2023

John Mascarenhas, MD

John Mascarenhas, MD, professor of medicine, the Icahn School of Medicine, Mount Sinai, director, the Center of Excellence for Blood Cancers and Myeloid Disorders, member, the Tisch Cancer Institute, Mount Sinai, discusses the role of pacritinib (Vonjo) in patients with myelofibrosis.

Pacritinib is JAK1-sparing, JAK2, FLT3, IRAK1, and ACVR1 inhibitor used in the treatment of patients with myelofibrosis in the setting of cytopenias at full dose to obtain spleen and symptom benefit, Mascarenhas says. In February 2022, the FDA granted an accelerated approval to pacritinib for the treatment of adult patients with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.

The approval was based on data from the phase 3 PERSIST-1 (NCT01773187), phase 3 PERSIST-2 (NCT02055781), and phase 2 PAC203 (NCT04884191) trials, a dose-finding study, and the ongoing phase 3 PACIFICA trial (NCT03165734) is serving as a confirmatory trial following the agent’s accelerated approval, Mascarenhas expands.

Although pacritinib is approved for patients with platelets less than 50 × 109/L , PERSIST-2 also produced data in patients with a platelet count of less than 100 x 109/L. Prior to the approval of pacritinib, clinicians did not have a JAK2 inhibitor available for patients with a platelet count below that could be administered at the full dose, Mascarenhas notes. The JAK2 inhibitors fedratinib (Inrebic) and ruxolitinib (Jakafi) have labels patients with platelet counts of 50 × 109/L and greater. Since those two agents are more myelosuppressive, clinicians must attenuate the dose when treating patients with a platelet count below 50 × 109/L, reducing the spleen and symptom benefit generated by fedratinib and ruxolitinib, Mascarenhas says. Twenty 20 mg of pacritinib given twice daily can be delivered to patients with platelet counts at 20 × 109/or less and still produce spleen and symptom benefits with a favorable toxicity profile, Mascarenhas continues.

Studies have not demonstrated an increased risk of cardiovascular events with pacritinib, and data have shown reduced myelosuppression. There may be an increased risk of bleeding with pacritinib, and patients who have a known coagulopathy, have bleeding diathesis, or are receiving anticoagulation should be counseled appropriately, Mascarenhas expands. Although it is important consider the potential benefits and risks for each individual patient, pacritinib does provide an efficacious treatment option for patients with myelofibrosis with low platelet counts, Mascarenhas concludes.

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Mar 9, 2023

Ashling Wahner

Treatment with ruxolitinib impaired antibody responses to complete vaccination with the BNT162b2 SARS-CoV-2 vaccine in patients with myelofibrosis or polycythemia vera.

Treatment with ruxolitinib (Jakafi) impaired antibody responses to complete vaccination with the BNT162b2 SARS-CoV-2 vaccine in patients with myelofibrosis or polycythemia vera (PV), according to findings from a prospective, single-center study.¹

After completing 2 doses of the vaccine, the average level of serum immunoglobulin G (IgG) neutralizing antibody levels against the receptor-binding domain portion of the spike protein of SARS-CoV-2 (anti-S) was 369.5 BAU/mL (range, 0-6901). Of the 43 patients who received 2 vaccine doses, 14 (32.6%) had anti-S antibody levels below the threshold for immunogenicity positivity, 27 had levels below 60 BAU/mL, and 28 had levels below 100 BAU/mL. Specifically, of the patients with myelofibrosis, 13 did not achieve an antibody response, and of those with PV, 1 did not achieve an antibody response.

Previously in 2020, results from the clinical trial investigating the efficacy of the BNT162b2 mRNA COVID-19 vaccine demonstrated that fully vaccinated patients gained 95% protection against the virus.² However, this trial did not include patients from certain fragile patient populations, such as immunocompromised patients, in whom the vaccine’s protection may be lower because of their ongoing treatments and diseases.

More recent studies have shown that the vaccine is less effective in patients with hemato-oncological diseases. Previous research with the vaccine in small cohorts of patients with myeloproliferative neoplasms (MPNs) treated with ruxolitinib has shown that these patients may exhibit lower responses to the first and second doses of the vaccine, and that responses differ across MPNs. For instance, a study investigating long-term responses to the vaccine in patients with essential thrombocythemia (ET), PV, and myelofibrosis receiving ruxolitinib showed that median antibody titers were 811 BAU/mL (range, 184->2500), 274 BAU/mL (range, 1.7->2500), and 51.4 BAU/mL (range, 0.6-529), respectively, over 1 month after the second vaccine dose.³

“As little data were available in [patients with MPNs] treated with ruxolitinib who had completed the vaccination cycle (2 doses) and a third booster dose, in this study, we investigated whether these patients could reach a protective antibody level against the SARS-CoV-2 virus,” lead study author, Giuseppe A. Palumbo, MD, PhD, of the University of Catania in Italy, and colleagues, wrote in a paper of the data published in Frontiers in Oncology.¹

This study evaluated 43 patients with primary myelofibrosis (n = 15), secondary myelofibrosis (n = 15), and PV (n = 13) who received ruxolitinib for their respective MPNs. All patients received both doses of the intramuscular BNT162b2 mRNA vaccine at 30 mcg per dose 3 weeks apart, per the Italian national guidelines. Patient sera samples were obtained at a median of 36 days (range, 14-53) after they received the second vaccine dose.

Of the 43 patients, 39 received the booster dose, 2 died before receiving the booster dose, and 2 refused the booster dose. Patients received their booster dose at a median of 153 days (range, 32-243) after their second dose. Sera samples were obtained from each patient before they received the booster dose, either on the same day or the day before, and at a median of 26 days (range, 11-49) following their booster dose.

All patients began ruxolitinib treatment at a median of 1236 days (range, 10-3370) before their first vaccine dose; 1414 days (range, 10-3288) for patients with myelofibrosis and 817 days (range, 53-3370) for those with PV. At the time of their first vaccine dose, patients were receiving ruxolitinib at a median of 14.7 mg twice daily (range, 2.5-25). The median ruxolitinib dose was 16.1 mg twice daily (range, 2.5-25) for patients with myelofibrosis and 11.5 mg twice daily (range, 5-15) for those with PV.

Of the patients with primary myelofibrosis, 2, 5, 7, and 1 had low-, intermediate-1–, intermediate-2–, and high-risk disease, respectively, when they received their first vaccine dose, per the Dynamic International Prognostic Scoring System (DIPSS). No patients had DIPSS score changes at the time of their booster dose. Of these patients, 13 had JAK2 V617F mutations, and 2 had CALR mutations.

Of the patients with secondary myelofibrosis, 1, 5, 5, and 4 had low-, intermediate-1–, intermediate-2–, and high-risk disease, respectively, when they received their first vaccine dose, per Myelofibrosis Secondary to PV and ET-Prognostic Model score. At the time of their booster dose, 1 patient each had progressed from low-risk to intermediate-1–risk disease and intermediate-2–risk to high-risk disease. Of these patients, 13 had JAK2V617F mutations, and 2 had CALR mutations.

Of the patients with PV, 12 had JAK2 V617F mutations and 1 had a JAK2 exon 12 mutation. All patients with PV had received hydroxyurea before switching to ruxolitinib. Seven patients switched because of hydroxyurea intolerance, and 6 patients switched because of hydroxyurea resistance per the European Leukemia Network consensus criteria.

At first vaccine dose, all patients had a median age of 69 years (range, 46-86); The median age was 72 years (range, 46-86) in patients with myelofibrosis and 64 years (range, 50-78) in those with PV. The overall median spleen size was 3 cm below the costal margin (range, 0-20), including a median of 4.6 cm (range, 0-20) in patients with myelofibrosis and 0 cm (range, 0-2) in those with PV.

This study evaluated vaccine immunogenicity by measuring the anti-S serum IgG neutralizing antibody levels. Per the World Health Organization, an anti-S value above 7 BAU was considered positive. The investigators also measured IgG against SARS-CoV-2 nucleocapsid proteins (anti-N) to determine whether patients had a prior or ongoing SARS-CoV-2 infection before or during vaccination.

Of all patients, 2 with primary myelofibrosis had anti-N IgG antibodies, indicating their exposure to SARS-CoV-2 prior to their first vaccine dose. These patients had a high post-vaccination antibody response, of 1333.9 BAU/mL and 6901.5 BAU/mL.

With 2 vaccine doses, patients achieved antibody levels at a median of 12.3 BAU/mL (range, 0-54.2). After the booster dose, patients reached a median antibody level of 272.3 BAU/mL (range, 0-1399). With the booster, 8/40 patients (20%), 7/27 with myelofibrosis and 1/12 with PV, did not achieve antibody levels above the positivity threshold. In total, 19 patients had antibody levels below 60 BAU/mL, and 24 had levels below 100 BAU/mL.

“Our study confirmed that [patients with] ruxolitinib-treated MPNs who have received 2 standard doses of BNT162b2 show a markedly impaired antibody production,” the study authors wrote. “Although the third booster dose was able to reduce the number of patients who remained fully negative, the median antibody value reached was not significantly better, and levels were far from those obtained with the same vaccine dose and schedule in normal subjects.”

The investigators recommend delaying ruxolitinib treatment in patients with myeloproliferative diseases until they have received at least 2 vaccine doses, and for patients and their caregivers to use COVID-19 risk mitigation strategies, including hygiene measures and social distancing.

References

1. Palumbo GA, Cambria D, La Spina E, et al. Ruxolitinib treatment in myelofibrosis and polycythemia vera causes suboptimal humoral immune response following standard and booster vaccination with BNT162b2 mRNA COVID-19 vaccine. Front Oncol. Published online February 14, 2023. doi:10.3389/fonc.2023.1117815
2. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577
3. Auteri G, Bartoletti D, Di Pietro C, et al. Longer-term response to SARS-CoV-2 vaccine in MPN patients: role of ruxolitinib and disease severity. Leuk Res. 2022;(5)116:106819. doi:10.1016/j.leukres.2022.106819

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Tania Jain, MBBS, director, Adult Chimeric Antigen Receptor T-cell Therapy Program for Hematological Malignancies, Sidney Kimmel Comprehensive Cancer Center, Assistant Professor of Oncology, Johns Hopkins Medicine, discusses the unmet needs for patients with myelofibrosis who receive an allogeneic stem cell transplant (allo-SCT).

At the 2023 Transplantation and Cellular Therapy Meetings, Jain presented data from a retrospective study evaluating outcomes for patients with myelofibrosis who had haploidentical donors (HD) and posttransplant cyclophosphamide vs other common donor types.

Findings from the study reflected that investigators still have considerable work to do in order to optimize allo-SCTs for patients with myelofibrosis, Jain begins. One area of need is relapse prevention, Jain says, adding that investigators are working to set up studies evaluating maintenance strategies post–allo-SCT to improve relapse rates.

Moreover, in the retrospective study, investigators showed that relapse rates were higher for patients with a larger spleen size going into transplant, Jain says. Novel agents currently under investigation in myelofibrosis could improve spleen response in patients, Jain continues. These could be beneficial for patients who will undergo allo-SCT, and it will be helpful to observe what a improved spleen responses with advanced therapies could mean for patients achieve in terms of transplant outcomes, Jain explains.

If patients with myelofibrosis are going to be referred for transplant, it should be done early before they have the chance to get worse or progress, Jain continues. The longer the patient is not referred, the quicker the window for transplant closes, and sicker patients do not do as well on clinical trials, Jain says. Moreover, it is important not to delay transplant looking for a perfectly matched donor when there are options with different donor types that can also help patients, which is important to consider, Jain concludes.

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At a live virtual event, Andrew Kuykendall, MD, discussed the rationale and data for the use of pacritinib in patients with high-risk primary myelofibrosis.

[There has been] a recent change in our understanding, like all things, that comes with having emerging medications that might be able to contribute to [treatment of] these more cytopenic patients. In the past, it wasn’t helpful to differentiate, because we didn’t have too many options, but it’s something that’s certainly growing in awareness. We often see that this proliferative phenotype is more consistent and almost resembles something like polycythemia vera or essential thrombocythemia.

On the other hand, we have the cytopenic phenotype, which is considered more aggressive from prognostic modeling and just overall outcomes, and perhaps that’s because we’re dealing with more mutations.¹ It’s a more complex picture and a less effective treatment, so it’s something I think we will hear more about as we go forward in the next few years as we try to get a better understanding of these patients.

I also think they can be 2 different diseases, but they’re 2 different kinds of phenotypes of a disease, and I think you can switch from one to another. Certainly you can have patients [who] present as cytopenic enough [with] typically just splicing mutations—more myelodysplastic syndrome-like mutations in conjunction with a JAK2 mutation—[who] tend to [also] present with lower platelet counts.²

[However], you can also have a patient [who] has more proliferative disease and then acquires new mutations, [which] contribute to this more cytopenic disease. Either way, you’re dealing with a more complex disease, with more mutations and bigger challenges to deal with as far as treatment goes. [In higher-risk patients], we have this decision point based on the platelets. [For a patient with] platelets greater than 50 × 10⁹ /L [who is] a transplant candidate, we certainly recommend going forward with that.³

The Role of Pacritinib

When patients have [a platelet count] less than 50,000, we used to say transplant was the only option, but now we have this emerging evidence for pacritinib, which is becoming more utilized. Pacritinib was added with a more recent update for patients with less than 50,000 platelets, but it also was added as a potential second-line option.⁴

When we talk about JAK inhibition, we have 3 approved therapies: ruxolitinib, fedratinib, and pacritinib.^5-7 All [these] have similarities in the sense that they inhibit JAK2, but they have some unique aspects. Ruxolitinib is a JAK1 and JAK2 inhibitor, fedratinib is mostly a JAK2 inhibitor but has some FLT3 inhibition, and pacritinib [also] has JAK2 and FLT3 inhibition, so these are more selective JAK2 inhibitors.

Pacritinib also has potential relevance in the sense that it inhibits CSF1R and IRQ1, and maybe this has some relevance as to how this is less myelosuppressive.⁸ Indications are similar for ruxolitinib and fedratinib, but pacritinib requires moderate thrombocytopenia, then the dosing is a stable flat dose for fedratinib and pacritinib. So 400 mg once daily for fedratinib, recommended to take with food to decrease some of this GI [gastrointestinal] toxicity.

Pacritinib [has the] same [recommendation regarding] being taken with food, but it’s given at 200 mg twice daily. Ruxolitinib is based on the platelet count, where there’s this dynamic dosing strategy to avoid causing severe thrombocytopenia. For patients with a platelet count of 50,000 to 100,000, [use] 50 mg twice a day. [If they have more than] 200,000 platelets, [use] 20 mg twice a day. Ruxolitinib has an inhibition of JAK1 and JAK2, but pacritinib [has] quite a difference between JAK1 and JAK2, and fedratinib is somewhere in between.

When you look at the impact of what not hitting JAK1 might be, JAK1 has a role in megakaryocytes releasing platelets, so if you inhibit that you tend to inhibit [not only] megakaryocyte maturation but also the release of platelets. If you don’t hit that, then maybe you’re just inhibiting megakaryopoiesis, but you’re not necessarily inhibiting the platelet production or the thrombopoiesis. Perhaps that’s why pacritinib is a little bit better tolerated in terms of platelet counts.

Highlights of the PERSIST Trials

PERSIST-1 [NCT01773187] was a frontline trial that looked at pacritinib in patients with any platelet count, but they couldn’t have had prior JAK inhibitors. [Patients were randomly assigned] 2:1 to pacritinib at 400 mg daily, which is not the recommended dose, vs the best available therapy [BAT], but the BAT could not be ruxolitinib.⁹ [The study then] looked at a primary end point of 35% [spleen volume reduction (SVR) at week 24].

For various reasons, we don’t look too much at PERSIST-1 now, because it’s kind of an obsolete dosing strategy. It doesn’t compare directly with ruxolitinib and doesn’t include prior ruxolitinib. [However], the PERSIST-2 study [NCT02055781] certainly has some relevance; it enrolled patients with thrombocytopenia [and] less than 100,000 platelets, and they were allowed to have had prior JAK inhibitor therapy.¹⁰

Patients were [randomly assigned] 1:1:1 to 2 different doses of pacritinib vs BAT, which could include ruxolitinib, then they looked at coprimary end points of spleen volume response and symptom response. When you look at the baseline demographics of this study, the important thing everyone wants to know is how much of BAT was ruxolitinib, and [approximately] 44% of patients received ruxolitinib as BAT.

Then when you look at the risk scores [of patients on this trial], it was more of an intermediate- to high-risk group, [with just over 50% in both groups being categorized as intermediate-2 risk scores]. The overall patient population was quite similar, but [approximately] 42% [in the pacritinib group] had platelets that were less than 50 × 10⁹ /L, and this is certainly the indication that it has now.

When you look at SVR at week 24 [for patients on the now] recommended dose of 200 mg twice daily, patients on pacritinib compared [with] BAT were more likely to achieve SVR at 29%, especially in those patients with less than 50×10⁹ /L platelets, compared [with] 3.1% in those patients [who] had BAT. It had quite a striking absolute difference between the 2 groups, at 25.9% [95% CI, 4.3%-44.5%].

When assessing the patients’ total symptom score [TSS], 32% of patients in the pacritinib arm compared [with] 14% in the BAT arm were able to achieve a TSS response of at least a 50% decrease in the symptoms.

[When looking specifically at the patients who had prior ruxolitinib as BAT], it seems like most of [them] were getting improvement in symptoms, albeit not to that 50% threshold, which may go along with the fact that they were getting suboptimal dosing. Furthermore, when we look at individual symptom scores in pacritinib vs BAT, across the board it seems to be that [those] in the thrombocytopenic patient population were getting better symptom improvement with pacritinib compared [with] BAT as well.

Reactions to Pacritinib

When considering red blood cell transfusions over time, we often think about pacritinib being used in this low-platelet population. You can compare pacritinib at 400 mg with 200 mg [with] BAT at baseline, and it looks like the BAT arm was getting [some] more transfusions on median number of transfusions for a month. [However], after week 12, the number of transfusions in the 200-mg twice daily arm decreases, whereas the number of infusions increases in the BAT arm.

Then at week 24, it decreases again in the pacritinib arm. Over time, [patients] on pacritinib—even those thrombocytopenic patient populations—are experiencing [fewer] red blood cell transfusions. When you look at the platelet counts and the trend over time, it appears that patients on pacritinib have a stable platelet count over these 24 to 36 weeks.

[Looking at adverse reactions to the therapy, there is still] the signal for GI toxicity. This often happens when [therapies] hit FLT3, as pacritinib does, like fedratinib. There is only 4% of patients in the pacritinib arm with grade 3 or greater diarrhea, but there is still a significant amount of diarrhea in [approximately] 50% of patients, [which is] much more than those on BAT.

We’re seeing a little more of other adverse reactions in pacritinib vs BAT: thrombocytopenia [34% vs 23%, respectively], nausea [32% vs 11%], anemia [24% vs 15%], edema [20% vs 15%], and vomiting [19% vs 5%]. The take-home message here is that there is more GI toxicity in some patients’ myelosuppression, although to a much milder extent than what we saw previously with ruxolitinib and fedratinib.

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Thu, March 2, 2023 at 8:35am EST

World-Renowned Physician-Scientist and Global Expert in Myeloproliferative Neoplasms

Will Be Instrumental in Advancing the Development of Navtemadlin and Other Innovative Therapies to Improve the Lives of Cancer Patients

REDWOOD CITY, Calif., March 02, 2023–(BUSINESS WIRE)–Kartos Therapeutics, Inc. (“Kartos” or the “Company”), a clinical stage biopharmaceutical company dedicated to the development of novel, targeted therapeutics that meaningfully improve the lives of patients with cancer, today announced that Dr. Srdan (Serge) Verstovsek, MD, PhD, has been named Chief Medical Officer (CMO).

Dr. Verstovsek is a world-renowned physician-scientist and a leading global authority on the treatment of myeloproliferative neoplasms (MPN), including myelofibrosis (MF). Since 1998, Dr. Verstovsek has been affiliated with the University of Texas MD Anderson Cancer Center where he served as hematologist-oncologist and more recently as the United Energy Resources, Inc. Professor of Medicine. He was also Director of the world’s largest MPN clinical research center, the Hanns A. Pielenz Clinical Research Center for MPNs, and Chief of the Section for MPNs.

Dr. Verstovsek has achieved international acclaim for pioneering practice-changing therapeutic advances for the treatment of MPNs. He has led more than 80 early/advanced phase clinical trials of novel MPN drugs, including ruxolitinib, which until 2019 was the only FDA-approved medication for myelofibrosis. He has published 24 book chapters, more than 600 peer-reviewed original articles/reviews in leading medical journals and has received numerous clinical research awards.

“We are humbled that Dr. Serge Verstovsek has decided to continue his extraordinary career as part of the Kartos team,” said Jesse McGreivy, MD, Chief Executive Officer of Kartos Therapeutics. “Serge’s deep understanding of MPNs and his accomplishments as a clinician and drug developer are unparalleled. Having Serge onboard will be tremendously impactful in our quest to bring navtemadlin and other innovative medicines to patients across the globe.”

“I am thrilled to join a Company so dedicated to developing novel, targeted therapeutics that meaningfully improve the lives of patients with cancer,” said Dr. Verstovsek. “Having worked closely with Kartos’ outstanding executive team and been deeply involved in designing several of the company’s studies, I know firsthand about the incredible talent and science driving the development of navtemadlin. I am very enthusiastic about the clinical potential of this groundbreaking drug and look forward to devoting the next stage of my career to help ensure its complete success.”

Dr. Verstovsek is a member of the American Society for Clinical Investigation and is co-founder and an Executive Committee Member of the International Working Group for MF Treatment and Research. Dr. Verstovsek received his MD and PhD from the University of Zagreb, Croatia.

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