Rigel Readies Tavalisse For Late-May Launch After FDA Approval

Rigel has its first US FDA approval for Tavalisse (fostamatinib) and plans to launch the drug for adults with immune thrombocytopenia (ITP) in late May, after working on the drug's development for more than a decade across multiple indications.

Rigel Pharmaceuticals Inc. has spent more than a decade developing Tavalisse (fostamatinib) across multiple indications and will finally launch the spleen tyrosine kinase (SYK) inhibitor in late May after the oral drug's US FDA approval on April 17 to treat adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a prior treatment.

Rigel President and CEO Raul Rodriguez told Scrip that the label "is exactly what we were hoping for" with a broad indication allowing treatment of adults with ITP after they've failed treatment with steroids, which is the typical first-line therapy. The company and analysts believe that Tavalisse also may have a commercial advantage over thrombopoietin (TPO) receptor agonists, because it is not an injection, like Amgen Inc.'s Nplate (romiplostim), and it does not have to be taken on an empty stomach nor does it carry a boxed warning about hepatotoxicity, like Novartis AG's Promacta (eltrombopag).

Rigel did not disclose the list price for Tavalisse and does not expect to offer that information or details about its patient assistance program and negotiations with payers until its first quarter earnings call on May 1.

"By the time we launch at the end of May, we will have all major payers agreed to in terms of the distribution system. Tavalisse will be available to virtually everyone by the end of May," Rodriguez said in an interview. "We're in late stages with virtually all payers."

Rigel has been building its commercial organization for more than a year and the company expects to have about 50 employees in that department, including 30 sales representatives, more than 20 of which already have been hired. (Also see "Rigel Downsizes R&D To Ready Fostamatinib Commercial Effort" - Scrip, 15 Sep, 2016.)

Rodriguez pointed out that Tavalisse will launch just in time for the company's sales reps to speak with physicians who treat chronic ITP during the American Society of Clinical Oncology (ASCO) meeting June 1-5; the drug will be prescribed largely by hematologists and oncologists.  

Novel Mechanism Provides Value

In terms of future marketing plans and ongoing discussions with payers, he said the treatment's value lies largely in its novel mechanism of action and patients' duration of response, since many chronic ITP patients don't respond or have a short-term response to first-line treatment with steroids and TPO agonists in the second line.

The SYK kinase is a mediator of immune cell signaling, including macrophages that destroy blood platelets in patients with ITP. Tavalisse addresses the underlying cause of the disease by inhibiting SYK in order to impede platelet destruction, while Nplate and Promacta work to stimulate platelet production.

Rodriguez also noted that Tavalisse is a relatively fast-acting therapy, with 60% of chronic ITP patients who responded to treatment in clinical trials having a response within two weeks. Patients with a low platelet count below 20,000 platelets/uL were able to get to 50,000 to 100,000 platelets/uL – a level necessary for blood to clot – and maintained that response for the long term.

ITP symptoms include excessive bruising, bleeding and fatigue. Patients with chronic ITP may have an increased risk of severe bleeding that can cause serious medical complications or death. About 50,000 to 60,000 people in the US have chronic ITP.

"We believe Tavalisse has advantages over TPO agonists (Nplate and Promacta), given oral administration, no food restriction and no black box warning," BMO Capital Markets analyst Do Kim wrote in an April 17 report. "While clinical response rates were lower than TPO, we believe physicians could maintain Tavalisse therapy in patients with greater than 30,000/uL platelet counts, which would represent a 43% response rate (clinically relevant platelet response)."

Outcomes-Based Contracts Unlikely Initially

Rigel reported in 2016 that about 18% of patients treated with Tavalisse in the first Phase III clinical trial in chronic ITP achieved platelet counts of 50,000/uL during at least four of six visits between weeks 12 and 24 of the study, which was statistically significant compared with no patients meeting that bar in the trial's placebo arm. (Also see "Rigel Optimistic On Fostamatinib Despite Narrow Phase III Benefit" - Scrip, 30 Aug, 2016.)

With less than one-fifth of patients having a significant response after 24 weeks of treatment, it's reasonable to assume that payers may want proof of a response within a certain timeframe in order to reimburse the drug. However, Rigel is not negotiating outcomes-based contracts at this time.

Chronic ITP "is not an area that's heavily managed" by payers, Rigel Executive Vice President and Chief Commercial Officer Eldon Mayer III said during the company's April 17 call. "We would look to have open access," Mayer said.

He also indicated that required patient monitoring shouldn't be a barrier to reimbursement for Tavalisse or impede patient access. Labeling requires blood pressure monitoring for hypertension every two weeks until the patient's platelets are stabilized and then monthly monitoring; monthly liver function testing to rule out hepatotoxicity; and monthly monitoring of neutropenia and for infections due to low neutrophil counts.

The most common side effects associated with Tavalisse in clinical trials were diarrhea, hypertension, nausea, respiratory infection, dizziness, increased liver enzymes, rash, abdominal pain, fatigue, chest pain and neutropenia.

Weill Cornell Medicine professor emeritus James Bussel, who was a principal investigator on the Phase III FIT trial program in chronic ITP and has served as a consultant and paid member of Rigel's advisory board, also noted during the company's call that he didn't think the safety monitoring requirements would be an undue burden for patients or for payers. Both are used to regular blood tests, especially when patients are treated with Promacta and must be monitored for liver abnormalities.

Future Indications, Ex-US Partners

As for additional Tavalisse indications, Rigel has a Phase II study under way in autoimmune hemolytic anemia (AIHA) and has seen a 53% response rate, so far. There are about 40,000 AIHA patients in the US with steroids as the only available treatment.

BMO's Kim predicted that Tavalisse could generate as much as $1.1bn in annual sales if the drug is approved in AIHA with a label as broad as its chronic ITP indication.

Rigel continues to evaluate Phase II results first reported in early April in the treatment of immunoglobulin A nephropathy (IgAN), an autoimmune disease in which the body makes antibodies to the IgA1 protein, leaving the kidneys unable to process blood.

The company already is looking for partners to commercialize Tavalisse in ex-US markets and Rodriguez noted that the drug's path forward in IgAN may be via development with a partner in Asia, where the disease is more prevalent.

"Rigel has been working on this product for well over 10 years. It's a very exciting moment for us to get our first product approved for" chronic ITP, Rodriguez said. He noted that many of the researchers at the company today were involved in discovery of the product, which before chronic ITP failed to find success in the clinic across at least seven cancer, hematology and autoimmune indications.

BMO's Kim said FDA approval of Tavalisse in chronic ITP should de-risk the drug for potential ex-US partners. The analyst noted that Rigel will meet with the FDA about the regulatory path in AIHA in the second quarter of 2018 and continue to pursue a filing for Tavalisse in chronic ITP by the fourth quarter of this year while partnership negotiations continue.

"We believe potential partners will be motivated by additional opportunities outside of ITP, including AIHA," Kim added.

Rigel previously was partnered with AstraZeneca PLC on the development of Tavalisse until the UK-based big pharma dropped out of the collaboration in 2013. (Also see " RIGEL: 30 job cuts, new fostamatinib-led strategy " - Scrip, 6 Sep, 2013.)