The FDA recently approved Rigel Pharmaceuticals’ Tavalisse (fostamatinib) for adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The drug will be the fifth official entry in the ITP armamentarium after intravenous immunoglobulin (IVIG) and Rho-Immunoglobulin (anti-RhD) treatments, and the two thrombopoietin receptor agonists (TPO-RAs)—orally administered eltrombopag (Novartis’s Promacta/Revolade) and subcutaneously administered romiplostim (Amgen’s Nplate). Although glucocorticoids (e.g. prednisone/prednisolone and dexamethasone) and immunomodulators (e.g. rituximab, azathioprine, cyclosporine) are widely used and considered effective in the management of the disease, these treatments are not FDA or EMA approved for ITP.

Tavalisse’s clinical data may seem modest, but there may be more than meets the eye. In the combined analysis of the pivotal clinical trials of Tavalisse in persistent/chronic ITP patients (two double-blind Phase III trials; FIT-1 and FIT-2), 18% of the Tavalisse-treated versus 2% of the placebo-treated achieved a stable platelet response, whereas 43% of fostamatinib-treated patients vs. 14% of placebo-treated had achieved overall response, a less stringent retrospectively defined endpoint. Tavalisse-treated patients did experience a greater number of serious and treatment-related adverse events compared with the placebo-treated subjects.1 In the combined analysis of data from the FIT-1 and FIT-2 and an ongoing open-label extension study, overall 22% of all the patients had achieved a stable platelet response until the last report, 68% of which continued to respond for ≥ 12 months.2

The response rates achieved by Tavalisse in its pivotal studies were not seemingly impressive compared with other available therapies in ITP, particularly the TPO-RAs, which are associated with response rates as high as 85%.3 However, unlike previous ITP trials, patients enrolled in the FIT trials were refractory to multiple treatments (median of 3 unique prior therapies and as many as 13) and had persistently low platelet counts (≤ 30,000/µl, with more than half below 15,000/µL) despite prior treatment with the TPO-RAs, rituximab, and/or splenectomy. Moreover, the median baseline duration of ITP in these patients was over 8 years, higher than in previously published ITP studies (2.37 years and 4 years in open-label studies of eltrombopag and romiplostim, respectively).3,4 A stable response of 22%, and an overall response of 43% in this population may be a silver lining for ITP patients who do not get adequate benefit from available treatments and are at risk of severe bleeding due to persistent thrombocytopenia.

Interviewed hematologists welcome Tavalisse but plan to reserve its use only for the most refractory patients: ITP experts interviewed by Decision Resources Group note that, given the high response rates and long-term safety and efficacy data of the available therapies, particularly the TPO-RAs, possibility of prescribing Tavalisse in favor of more established therapies is very low. Physicians are also concerned about the unfavorable tolerability profile of Tavalisse in the pivotal clinical trials, and see it as a barrier to wider uptake of this drug. They further note that the poorly understood patient heterogeneity and lack of prognostic biomarkers in ITP impact their treatment decisions. Available clinical data does not delineate between Tavalisse-responders vs. -non-responders, and thus they will continue to follow existing treatment algorithms, which will place Tavalisse as a later-line therapy. Nonetheless, interviewed experts contend that they would be willing to use Tavalisse earlier in the treatment, provided robust prognostic biomarkers and/or supportive clinical data become available. Currently, no such studies are on the horizon and, therefore, Tavalisse will likely be prescribed as a last-line therapy in ITP for the foreseeable future, for patients who are refractory or unresponsive to steroids, TPO-RAs, and rituximab or other immunomodulators–a small but significant percentage of the chronic ITP patient population.

Tavalisse may not face major payer pushback, but may still carry prescribing restrictions such as a step therapy protocol requiring prior authorization: Rigel recently announced that Tavalisse will have a list price of $9,450/month ($113,400/year), with a flat pricing for the 100 mg and 150 mg doses—an approximate 15% premium over that of eltrombopag 50 mg pill. The price point could be hard to justify for a drug that benefits a meaningfully lower percentage of patients than an established therapy; however, given that it is aimed at a hard-to-treat, niche patient population of ITP, Tavalisse may not face major payer pushback in the United States, particularly in the context of high-cost orphan drugs that have been launched in recent years for diseases with similar/lower target patient population sizes. Nonetheless, Rigel may find it challenging to justify Tavalisse’s prolonged use in unresponsive ITP patients, thereby prompting payers to make step therapy and/or other prior authorization criteria mandatory for the patients to get access to Tavalisse.

Tavalisse is unlikely to transform the treatment landscape of ITP but will partly fulfill a crucial unmet in the disease. Tavalisse has a novel mechanism of action that inhibits SYK (spleen tyrosine kinase), a crucial target in the immune signaling pathway that leads to platelet phagocytosis. No other available therapy for ITP targets a specific event in the disease pathophysiology. Nevertheless, despite a novel mechanism of action and positive clinical data, Tavalisse is unlikely to take the ITP treatment landscape by storm the same way the TPO-RAs did following their launch almost a decade ago. With high efficacy and response rates, a good safety and tolerability profile, and the long-term post-marketing data and physician comfort, the TPO-RAs enjoy an uncontested reputation in ITP treatment, and Tavalisse, in the context of available clinical data, is unlikely to challenge that perception. Nonetheless, the drug will fill the void for a potentially effective treatment for multiple-refractory patients in ITP, allowing it to claim a niche space in the ITP market.

  1. Bussel J, et al. Fostamatinib for the Treatment of Adult Persistent and Chronic Immune Thrombocytopenia: Results of Two Phase 3, Randomized, Placebo-Controlled Trials. Am J Hematol. 2018.
  2. Bussel J, et al. Long-Term Maintenance of Platelet Responses in Adult Patients with Persistent/Chronic Immune Thrombocytopenia Treated with Fostamatinib: 1-Year Efficacy and Safety Results. Blood. 2017; 130:16
  3. Wong RSM, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(23):2527-2536.
  4. Kuter DJ, et al. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol. 2012;87(5):558-561.


For DRG’s in-depth analysis of the Immune Thrombocytopenic Purpura market, read our Niche & Rare Disease Landscape & Forecast | Immune Thrombocytopenic Purpura market | US/EU5 content. Contact us to learn more about our US and EU5 orphan drug market access and reimbursement content.

Related Reports:

Immune Thrombocytopenic Purpura [ Disease Landscape & Forecast ]

Immune Thrombocytopenic Purpura [ Epidemiology Mature Markets Data ]

Immune (Idiopathic) Thrombocytopenic Purpura [ Niche & Rare Disease Landscape & Forecast | US/EU5 | 2016 ]

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Akash Saini, Ph.D., is a Lead Analyst with the Infectious, Niche, and Rare Diseases team at Decision Resources Group, where he specializes in a diverse group of rare diseases. He received his Ph.D. in biochemistry and biotechnology from the International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India and his M.Sc. in biotechnology from Jawaharlal Nehru University, New Delhi, India. Prior to joining Decision Resources Group, Akash was a postdoctoral fellow at the University of Massachusetts Medical School, where he studied mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS).

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