2023-03-09 05:59:46 ET
Summary
- Rigel Pharma has 2 FDA-approved drugs: Tavalisse for chronic immune thrombocytopenia (ITP) and Rezlidhia for relapsed or refractory AML with susceptible IDH1 mutation.
- In Q4 2022, Tavalisse revenue slightly rose, yet its utilization in ITP remains restricted. The future potential of Rezlidhia in AML treatment is unclear due to the changing treatment landscape.
- Rigel has $58.2M in cash and believes it's enough to continue operations for 12 months.
- I would prefer Rigel to tackle their financial situation and establish Rezlidhia's position in the treatment landscape before considering investment. In my opinion, Rigel stock is currently a "Hold" with a higher likelihood of downside until these concerns are addressed.
Introduction
Rigel Pharmaceuticals ( RIGL ) is a biotechnology company based in South San Francisco, California, that aims to discover, develop, and provide novel small molecule drugs that significantly improve the lives of patients with hematologic disorders, cancer, and rare immune diseases. Rigel Pharmaceuticals has developed two drugs, Tavalisse & Rezlidhia , which have been approved by the FDA for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia [ITP] who have had an insufficient response to a previous treatment, and adult patients with relapsed or refractory AML with susceptible IDH1 mutation, respectively.
Rigel's product portfolio (Rigel 10-K)
Financials
Let's first review financials. Rigel reported a net income of $1.4 million, or $0.01 per basic and diluted share, for the fourth quarter of 2022, compared to a net loss of $22.6 million, or $0.13 per basic and diluted share, for the same period in 2021. The company's total revenues for the fourth quarter of 2022 were $51.3 million, and its total costs and expenses were $49.2 million. For the full year 2022, Rigel reported a net loss of $58.6 million, or $0.34 per basic and diluted share, compared to a net loss of $17.9 million, or $0.11 per basic and diluted share, for the same period in 2021. The company had total revenues of $120.2 million for the full year 2022 and total costs and expenses of $175.8 million.
Rigel's Q2 2022 Financial Highlights (Rigel Pharmaceuticals)
As of December 31, 2022, Rigel had cash, cash equivalents, and short-term investments of $58.2 million. Rigel believes this is sufficient to continue operations for "at least the next 12 months".
This article will analyze the potential of Rezlidhia & Tavalisse in their respective markets.
Tavalisse Achieves Stable Platelet Responses in Chronic ITP Patients
Tavalisse , an oral SYK inhibitor, effectively increases platelet counts and achieves stable platelet responses in patients with chronic ITP who had an insufficient response to previous treatments. In Study FIT-1, 18% of patients on Tavalisse achieved a stable platelet response compared to none on placebo, while in Study FIT-2, 16% of patients on Tavalisse achieved a stable platelet response compared to 4% on placebo. The drug was well-tolerated, and rescue medication was required less often in patients receiving Tavalisse. The incidence of bleeding was similar between treatment arms. Patients who had received prior treatment with thrombopoietin receptor agonists (TPO-RA) and had lost response to them achieved stable platelet responses with Tavalisse. During the placebo-controlled studies, the incidence of bleeding occurred in 29% and 37% of patients in the Tavalisse and placebo arms, respectively, with moderate, severe, and serious bleeding events being similar between treatment arms.
REZLIDHIA Shows Efficacy in Relapsed/Refractory AML Patients with IDH1 Mutation
The efficacy of Rezlidhia , an IDH1 inhibitor, was evaluated in 147 adult patients with relapsed or refractory AML and an IDH1 mutation. The study measured efficacy based on CR+CRh rate, duration of CR+CRh, and conversion from transfusion dependence to independence. Results showed that 35% of patients achieved CR+CRh with a median duration of 25.9 months, while 32% achieved CR with a median duration of 28.1 months. Only 2.7% of patients achieved CRh, with observed durations ranging from 1.8 to 28.5+ months. The median follow-up and treatment durations were 10.2 months and 4.7 months, respectively.
Stepwise Approach to Treating Chronic Immune Thrombocytopenia: From First-Line to Third-Line Therapy
Treatment of chronic immune thrombocytopenia [ITP] typically involves a stepwise approach, beginning with corticosteroids, which can be effective in 60-70% of patients. If patients do not respond to corticosteroids or have a relapse after treatment, they may receive other treatments such as intravenous immunoglobulin, thrombopoietin receptor agonists, and splenectomy.
Treatment | Platelet Count Threshold | Goal | Considerations |
---|---|---|---|
First-Line Therapy | <30,000/microL | Provide a safe platelet count to prevent clinically important bleeding | Prednisone is the most commonly used first-line therapy; IVIG can also be used |
Second-Line Therapy | <20,000/microL | Provide a safe platelet count to prevent clinically important bleeding | Choice of therapy is individualized; options include splenectomy (curative ~85% of time), rituximab, or a thrombopoietin receptor agonist (TPO-RA) |
Third-Line Therapy | N/A | Individualized | Options include fostamatinib, immunosuppressive agents, danazol, dapsone, and combinations |
UpToDate, a popular resource amongst clinicians, recommends Rigel's Tavalisse for third-line therapy.
Treatment Options AML with IDH1 Mutation: Azacitidine Plus Ivosidenib Preferred Over Azacitidine Alone
For patients with newly-diagnosed AML and a susceptible IDH1 mutation, the current treatment options include azacitidine (Vidaza) plus ivosidenib ( Tibsovo ), which is recommended over Vidaza alone due to superior survival rates. If Tibsovo is not available, venetoclax (BCL-2 inhibitor) plus a hypomethylating agent [HMA] is preferred. Single-agent Tibsovo is acceptable for patients who cannot tolerate an HMA. For those who are ineligible for HMA therapy, alternative treatments are available.
Ivosidenib versus Rezlidhia for Relapsed or Refractory AML with Susceptible IDH1 Mutation
Prior to Tibsovo being approved in combination with Vidaza, it served as treatment for relapsed/refractory [R/R] AML with susceptible IDH1 mutation.
Below are trial comparisons of Tibsovo & Rezlidhia in R/R AML with IDH1 mutation:
Endpoint | TIBSOVO (500 mg daily) N=174 | REZLIDHIA (150 mg twice daily) N=147 |
---|---|---|
CR + CRh rate | 32.8% (95% CI: 25.8-40.3%) | 35% (95% CI: 27-43%) |
Median duration of CR+CRh | 8.2 months (95% CI: 5.6-12) | 25.9 months (95% CI: 13.5-NR) |
CR rate | 24.7% (95% CI: 18.5-31.8%) | 32% (95% CI: 25-40%) |
Median duration of CR | 10.1 months (95% CI: 6.5-22.2) | 28.1 months (95% CI: 13.8-NR) |
CRh rate | 8% (95% CI: 4.5-13.1%) | 2.7% (95% CI: 0.7-6.8%) |
Median overall survival | 10.3 months | 11.6 months |
Observed duration of CRh | 3.6 months (95% CI: 1-5.5) | 1.8, 5.6, 13.5, 28.5+ (95% CI: NR-NR) |
Median time to CR or CRh | 2 months | 1.9 months |
Transfusion independence in patients independent at baseline | 37.3% | 34% |
Transfusion independence in RBC/platelet dependent patients | 59.4% | 64% |
Abbreviations used:
- CR: complete remission
- CRh: complete remission with partial hematologic recovery
- CI: confidence interval
- NR: not reached
- CR+CRh rate: rate of complete remission plus complete remission with partial hematologic recovery
- Observed duration of CRh: duration of complete remission with partial hematologic recovery as observed in the study.
Below are the label adverse reactions for Rezlidhia & Ivosidenib, respectively.
REZLIDHIA label (FDA) TIBSOVO label (FDA)
Although efficacy and safety appear comparable between trials, the approval of Tibsovo (IDH1 inhibitor) in combination with Vidaza for newly diagnosed IDH1-mutant AML may leave Rezlidhia with a limited role in the treatment paradigm. Currently, Rezlidhia is only approved for use in relapsed or refractory AML patients with IDH1 mutations. However, Rezlidhia may still be considered as an option in certain cases, such as for patients who have previously received Tibsovo and Vidaza, or those who are unable to tolerate these treatments.
Conclusion
Rigel's portfolio includes two niche drugs, Rezlidhia & Tavalisse, with potential in their respective markets. Tavalisse is expected to generate modest revenue in later lines of ITP, potentially reaching a peak of around $200 million in annual sales. Rezlidhia's potential is uncertain due to the evolving treatment landscape for AML with susceptible IDH1 mutation. Although nearly half of newly-diagnosed AML patients with a susceptible IDH1 mutation do not respond to Tibsovo plus Vidaza, it is unclear if prescribers will use Rezlidhia (another IDH1 inhibitor after disease progression with a IDH1 inhibitor) for R/R AML as it was trialed prior to the change in the first-line standard-of-care. Recall, Rigel acquired Rezlidhia from Forma Therapeutics in August (months following Tibsovo-Vidaza data) for a modest upfront payment of $2 million, with additional payments of up to $230 million contingent on regulatory and commercial milestones. Despite a promising increase in Q4 2022 revenue, Rigel's cash runway is limited, and they may need to take on more debt or offer shares at the expense of investors.
I would prefer Rigel to tackle their financial situation and establish Rezlidhia's position in the treatment landscape before considering investment. In my opinion, Rigel is currently a "Hold" with a higher likelihood of downside until these concerns are addressed.
For further details see:
Rigel Pharmaceuticals' Challenges Continue To Outweigh Potential Upside