Technical Analysis
Short-Term Resistance: ~$66
Short-Term Support: ~$56

Agios Pharmaceuticals, Inc. is a company I see potential value in. From a technical analysis standpoint, it appears a reversal was confirmed in 2019 and has trended positively. It appears to have met a resistance around $66 and currently found a support near $56. If the support is confirmed, Agios may continue following their positive trend. I have not taken a position; however, this company is currently on my watch list. This company currently has two approved products, TIBSOVO® (ivosidenib) and IDHIFA® (enasidenib), and three other products in clinical development.  

TIBSOVO® (ivosidenib) is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test⁴. Isocitrate dehydrogenase mutations result in accumulation of oncometabolite 2-hydroxyglutarate, which causes epigenetic changes and impaired cellular differentiation.³  Agios is seeking a new indication for TIBSOVO® for the treatment of patients with newly diagnosed acute myeloid leukemia with an IDH1 mutation not eligible for standard therapy with a Prescription Drug User Fee Act (PDUFA) date of 21 June 2019.

Efficacy Results

The supplemental new drug application (sNDA) submission for the indication of treatment of patients with newly diagnosed AML with IDH1 mutation not eligible for standard therapy is based on results from phase 1, single-arm, open-label, multicenter, dose escalation and expansion study of ivosidenib (NCT02074839). This study is currently active but is not recruiting subjects. The study describes the preliminary analysis of ivosidenib effect on remission and transfusion independence in patients with IDH1-mutant untreated AML.

The primary efficacy endpoint is complete response (CR) + CR with partial hematologic recovery (CRh). Additional endpoints include objective response rate (ORR), CR, duration of response, time to response. The response definitions are modified criteria from the International Working Group recommendations from 2013. The response definitions are summarized in Table 1.² As of 11 May 2018, all patients with enrolled with untreated AML received ivosidenib starting dose of 500 mg once daily (n=34) (Table 2). Efficacy results are summarized in Table 3.³

Table 1. Response Definitions²

Response	Bone Marrow Blasts (%)	ANC (/μL)	Platelets (/μL)
CR	<5	>1000	>100,000
CRh	<5	>500	>50,000
CRi	<5	<1000	>100,000
CRp	<5	>1000	<100,000
MLFS	<5	–	–
PR	525 (>50% reduction)	>1000	>100,000

CR, complete response; CRh, CR with partial hematologic recovery; CRi, CR with incomplete hematologic recovery; CRp, CR with incomplete platelet recovery; MLFS, morphologic leukemia-free state; PR, partial response; ORR, objective response rate

Table 2. Baseline Characteristics

Characteristic	Untreated AML 500 mg (n=34)a
Women / men, n	15 / 19
Age in years, median (range) Age category, n (%) 60 to <75 ≥75	76.5 (64–87) 15 (44.1) 19 (55.9)
ECOG PS at baseline, n (%) 0 1 2 3	8 (23.5) 20 (58.8) 5 (14.7) 1 (2.9)
Nature of AML, n (%) De novo Secondary      History of MDS     History of MPD     Treatment-related     Other	7 (20.6) 27 (79.4) 18 (52.9) 4 (11.8) 4 (11.8) 1 (2.9)
Prior hypomethylating agent, n (%)	14 (41.2)
Cytogenetic risk status by investigator, n (%) Intermediate Poor Unknown	24 (70.6) 9 (26.5) 1 (2.9)

^aOne patient enrolled in dose escalation was positive for the IDH1-D54N mutation by local testing and was not positive for the IDH1-R132 mutation by the companion diagnostic test
ECOG PS = Eastern Cooperative Oncology Group Performance Status; MDS = myelodysplastic syndrome; MPD = myeloproliferative disease

Table 3. Efficacy Results

Untreated AML 500 mg (n=33)a
CR+CRh rate, n (%) [95% CI]      Time to CR/CRh, median (range), months Duration of CR/CRh, median [95% CI], months	14 (42.4) [25.5, 60.8] 2.8 (1.912.9)NE [6.5, NE]
CR rate, n (%) [95% CI] Time to CR, median (range), months Duration of CR, median [95% CI], months	10 (30.3) [15.6, 48.7] 2.8 (1.94.6)NE [4.2, NE]
CRh rate, n (%) [95% CI] Time to CRh, median (range), months Duration of CRh, median [95% CI], months	4 (12.1) [3.4, 28.2] 3.7 (1.912.9) 8.3 [6.5, NE]
ORRb by IWG, n (%) [95% CI] Time to first response, median (range), months Duration of response, median [95% CI], months	19 (57.6) [39.2, 74.5] 1.9 (0.93.6)NE [6.5, NE]
Best response by IWG, n (%)     CR     CRi or CRp     PR     MLFS     SD     PD     NA	10 (30.3) 6 (18.2) 1 (3.0) 1 (3.0) 10 (30.3) 3 (9.1) 2 (6.1)

^an=33, based on patients confirmed positive for mIDH1 by the companion diagnostic test
^bORR includes CR, CRi/CRp, MLFS, and PR
NE = not estimable; PD = progressive disease; PR = partial response; SD = stable disease

CONCLUSION:

Ivosidenib induced a durable response with a CR+CRh rate of 42%, lower bound of a 95% confidence interval of 6.5 months, and an objective response rate of 58%. The median duration for both the primary objective and the ORR were not estimable due to the study being ongoing.

REFERENCES

1. Agios Announces FDA Acceptance of Supplemental New Drug Application for TIBSOVO® (ivosidenib) for the Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation Not Eligible for Standard Therapy.; (2019). Available at  http://investor.agios.com/news-releases/news-release-details/agios-announces-fda-acceptance-supplemental-new-drug-application
2. Cheson BD et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9.
3. Roboz GJ et al. Ivosidenib (AG-120) induces durable remissions and transfusion independence in patients with IDH1-mutant untreated AML: Results from a phase 1 dose escalation and expansion study. Poster presented at the 60th American Society of Hematology (ASH) Annual Meeting;December 1–4, 2018; San Diego, CA.
4. TIBSOVO® (ivosidenib) tablets [Prescribing Information, 2018]. Agios Pharmaceuticals, Inc., Cambridge, MA

Disclosure: I have no positions in the stock mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions and not of those of my employer. I am not receiving compensation for it. I have no business relationship with the company whose stock is mentioned in this article.