Global Acute Myeloid Leukemia (AML) Disease Analysis 2020: Average Probability a Drug Advances from Phase III is 54.2%

DUBLIN, Sept. 14, 2020 /PRNewswire/ -- The "Disease Analysis: Acute Myeloid Leukemia (AML)" drug pipelines has been added to ResearchAndMarkets.com's offering.

The publisher estimates that in 2018, there were 158,400 incident cases of acute myeloid leukemia (AML) worldwide, and expects that number to increase to 169,000 incident cases by 2027. Approximately 60% of newly diagnosed patients are eligible for intensive chemotherapy, such as the 7+3 regimen of cytarabine and daunorubicin.

In the last three years, there have been eight new drugs approved for AML in the US, dramatically changing the treatment landscape. Gone is the era where all front-line patients received either 7+3 chemotherapy or a hypomethylating agent (decitabine or azacitidine). Many of the new therapies target specific segments of AML or patients with specific mutations. As such, there is currently little competition between the new therapies, but that will change as therapies receive label expansions and new competitor therapies are approved.Two FLT3 inhibitors have been approved for FLT3-mutated AML: Rydapt for front-line patients eligible for intensive chemotherapy, and Xospata for relapsed/refractory patients. Rydapt may soon face competition in the front-line FLT3 setting as quizartinib and Xospata are being evaluated in combination with standard chemotherapy and as single-agent maintenance therapies following either chemotherapy consolidation or bone marrow transplant. Crenolanib is also being evaluated as maintenance therapy after standard induction chemotherapy and consolidation. Approval in the lucrative maintenance setting would give these drugs a favorable long-term commercial outlook. Approximately 25-30% of AML patients have an FLT3 mutation.

Tibsovo and Idhifa are approved as oral, single-agent therapies for relapsed/refractory AML patients with IDH1 and IDH2 mutations, respectively. Tibsovo is also approved as a monotherapy for front-line patients over the age of 75 years. Both of these IDH inhibitors are now in Phase III trials in combination with standard induction (7+3) and consolidation chemotherapy in front-line AML. In addition, Tibsovo is being investigated in combination with azacitidine in a Phase III trial recruiting front-line patients. Tibsovo may face competition from FT-2102, an IDH1 inhibitor being evaluated in the relapsed/refractory setting in a pivotal single-arm Phase II trial both as monotherapy and in combination with azacitidine. IDH1 mutations are present in 6-9% of AML, while IDH2 mutations are present in approximately 12% of cases.

Mylotarg, an antibody-drug conjugate targeting CD33, is the only monoclonal antibody therapy approved for AML. Mylotarg combined with intensive chemotherapy is recommended for newly diagnosed patients with favorable cytogenetic risk (approximately 10% of patients eligible for intensive chemotherapy). Over 90% of AML patients are positive for CD33 expression.

Vyxeos, a liposomal formulation of the 7+3 chemotherapy regimen, was approved in the US and EU for the treatment of newly diagnosed patients with secondary AML after showing an improvement in overall survival compared to the 7+3 regimen in patients 60 years of age. Secondary AML accounts for approximately one third of new AML diagnoses, but most of these patients will be too frail for Vyxeos. Approximately 16% of patients eligible for intensive chemotherapy have secondary AML. Market access for Vyxeos is strengthened by positive recommendations from the US Centers for Medicare and Medicaid Services and from NICE in England and Wales.

Venclexta combined with azacitidine is the new standard of care for newly diagnosed AML patients not suited for intensive chemotherapy (approximately 40% of newly diagnosed patients). This combination demonstrated a survival advantage in a confirmatory Phase III trial, which should assure conversion of Venclexta's conditional FDA approval to a full approval. The Phase III trial will also be the basis for regulatory submissions to European and Japanese authorities. Daurismo is the first and only Hedgehog pathway inhibitor approved for AML. Daurismo is approved in combination with lowdose cytarabine (LDAC) for newly diagnosed AML patients not suited for intensive chemotherapy, and will compete with Venclexta in this difficult-to-treat setting. However, in the US, hypomethylating agents are preferred over LDAC, so Venclexta may be preferred over Daurismo.

Oral Vidaza increased overall survival and relapse-free survival in a Phase III trial and is currently under regulatory review in the US and EU as a maintenance therapy following intensive chemotherapy for patients not suited for a bone marrow transplant. The maintenance setting would be a new setting for Vidaza, as intravenous/subcutaneous Vidaza is currently used in the EU (and off-label in the US) to treat newly diagnosed elderly AML patients.

Chimerix's dociparstat sodium (DSTAT), a glycosaminoglycan analog of heparin designed to have reduced anticoagulant effects, targets the CXCR4 pathway which is involved in the homing and adhesion of AML cells to the bone marrow and is associated with resistance to systemic drugs. DSTAT is being developed in combination with intensive 7+3 chemotherapy for newly diagnosed AML, with the aim of improving the rate of durable response. A Phase III trial is enrolling patients with intermediate or unfavorable cytogenetic risk (74% of patients eligible for intensive chemotherapy).

While Xospata, Tibsovo, and Idhifa have been approved for the relapsed/refractory setting, they only target patients with mutations in FLT3, IDH1, or IDH2, respectively. Relapsed/refractory AML remains an area of unmet need, and new therapies are being developed. Not including FLT3 or IDH inhibitors, there are currently six late-stage therapies being evaluated for this setting (devimistat, DFP-10917, flotetuzumab, guadecitabine, Iomab-B, and uproleselan).

Key recent events include the presentation of numerical data from Venclexta's VIALE-A trial at ASCO 2020, and the Phase III failures of Helsinn's pracinostat and Roche's idasanutlin.

Key upcoming catalysts for 2020 include the expected US approval of oral azacitidine and top-line results from Phase III trials for uproleselan and CPI-613.

The overall likelihood of approval of a Phase I AML asset is 7.5%, and the average probability a drug advances from Phase III is 54.2%. AML drugs, on average, take 10.7 years from Phase I to approval, compared to 9.4 years in the overall oncology space.

Key Regulatory Events

• Xospata Reimbursement Marks a First for AML in England
• Keeping Track: Targeted Oncologics Take Center Stage, Led by Retevmo and Trabecta Approvals
• CHMP Adopts a Positive Opinion for Daurismo
• NICE Draft Guidance: Rejects Keytruda in Head & Neck Cancer, Xospata in AML
• Daiichi Sankyo Plays Long Game with Quizartinib Outside Japan
• Kiadis Crushed by EMA Rejection of T-Cell Therapy

Licensing and Asset Acquisition Deals

• Agios announces that it will receive $255m from Royalty Pharma
• Gilead Calls Forty Seven Buyout Complementary to Kite, Other IO Efforts
• Apollomics Gains China-Plus Rights to GlycoMimetics' E-Selectin Antagonists
• Finance Watch: Forma Raises $100m in Quest to become a Sickle Cell Leader
• BerGenBio, Piramal Pharma Strike Deal for Bemcentinib
• Immuno-Oncology Continues to Draw Pharma Companies to the Deal Table
• With Celgene Acquisition Closed, Bristol Faces Major Milestones
• Astellas Licenses Vector Cell Technology from RiKen
• Chimerix Licenses AML Candidate from Cantex
• Servier Deal Termination Fails to Dent MacroGenics' Flotetuzumab Optimism
• Ono Licenses Rafael's Novel Chemo-Sensitizing Agent for Asia

Future Trends

• New drug launches, including therapies for relapsed/refractory disease, will drive growth in the AML market over the forecast period
• FLT3 inhibitors are expected to move into the first-line maintenance setting
• IDH inhibitor combinations are expected to move into earlier stages of AML
• Oral hypomethylating agents are under development in AML

Companies Mentioned

• Apollomics
• Astellas
• BerGenBio
• Chimerix
• Daiichi Sankyo
• Forma
• GlycoMimetics
• Kiadis
• MacroGenics
• Medigene
• Piramal Pharma

For more information about this drug pipelines report visit https://www.researchandmarkets.com/r/4wpzx7

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