Rigel Pharmaceuticals Enters Collaboration and License Agreement with Grifols, S.A. to Commercialize Fostamatinib in Europe
SOUTH SAN FRANCISCO, Calif., -Rigel Pharmaceuticals, Inc.?(Nasdaq: RIGL) today?announced that it has entered into an exclusive license and supply agreement with?Spain-based?Grifols, S.A?(MCE: GRF, MCE: GRF.P, NASDAQ: GRFS) to commercialize fostamatinib?disodium hexahydrate in all potential indications in?Europe?and?Turkey.?Grifols?is a global healthcare company and a leading producer of plasma-derived medicines for the treatment of rare and chronic diseases, including intravenous immunoglobulin (IVIG) which is used in the treatment of ITP and AIHA. Fostamatinib is commercially available in the U.S. under the brand name TAVALISSE??(fostamatinib disodium hexahydrate) and is the first and only SYK inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to previous treatment.
"Grifols?has a broad presence in?Europe?and an established position in the hematology commercial landscape, which supports our goal of bringing fostamatinib to patients in these countries," said?Raul Rodriguez, President, and CEO of Rigel. "Our marketing authorization application for fostamatinib in chronic ITP is currently under review by the?European Medicines Agency, and we anticipate a decision by the end of 2019. This provides a potential opportunity for fostamatinib to begin generating revenue in the European market in 2020."
Under terms of the agreement, Rigel will receive a?$30 million?upfront cash payment, with the potential for?$297.5 million?in payments related to regulatory and commercial milestones, which includes a?$20 million?payment for EMA approval of fostamatinib for the treatment of chronic ITP. Rigel will receive significant stepped double-digit royalty payments based on tiered net sales which may reach 30% of net sales. In return,?Grifols?receives exclusive rights to fostamatinib in human diseases, including chronic ITP, autoimmune hemolytic anemia (AIHA), and IgA nephropathy (IgAN), in?Europe?and?Turkey. In the event that, in 2021, after the second anniversary of the agreement, fostamatinib has not been approved by the EMA for the treatment of ITP in?Europe,?Grifols?will have the option during a six-month time-frame to terminate the entire agreement which would terminate all their rights to ITP, AIHA, and all other indications.? In this limited circumstance, Rigel will pay?Grifols$25 million?and regain all rights to fostamatinib in?Europe?and other territories.? Rigel retains the remaining global rights to fostamatinib outside the?Grifols?territories and those rights previously granted to?Kissei Pharmaceuticals?(in?Japan,?China,?Taiwan?and the?Republic of Korea).
"Given our global leadership position as a manufacturer of plasma medicines and our in-depth knowledge and expertise in blood disorders, adding fostamatinib to our portfolio is a natural fit for?Grifols," said?Joel Abelson, President,?Bioscience Commercial Division of Grifols. "Its potential in multiple indications, including ITP, may provide significant benefit for patients and is a valuable addition to our portfolio."
On?October 4, 2018, the EMA validated the marketing authorization application?for fostamatinib in adult chronic ITP, which was submitted by Rigel. The company anticipates a decision from the EMA's Committee on Human Medicinal Products by the fourth quarter of 2019 and potential European approval by the end of 2019.
About ITP
In patients with ITP, the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing.? Common symptoms of ITP are excessive bruising and bleeding.? People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death.? Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.
About TAVALISSE
Indication?
TAVALISSE??(fostamatinib disodium hexahydrate) tablets is indicated in the US for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Important Safety Information
Warnings and Precautions
- Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
- Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
- Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (=Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
- Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
- TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
- Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
- It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
- Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
- Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
- Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
- Common adverse reactions (=5% and more common than placebo) from the FIT-1 and FIT-2 phase 3 clinical trials included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.