Recent Launches for Acute Myeloid Leukemia (AML)
What We’ve Learned

Advancements in medicine have equipped physicians to assign distinct prognostic groups to patients with AML based on their cytogenetic data. On April 28, 2017, the US Food and Drug Administration (FDA) approved midostaurin (Rydapt®) by Novartis Pharmaceuticals, Inc., for the treatment of adults recently diagnosed with FLT3-mutated acute myeloid leukemia (AML). Rydapt® is an oral, multi-targeted inhibitor that targets mutations in FLT3, a type III receptor tyrosine kinase.

Approximately 25% to 30% of patients with AML have mutations in FLT3, a number consistent with Medimix LiveTrackerTM Real World Evidence measure of 26% (based on 703 patients treated in the US market). These mutations occur due to internal tandem duplication (ITD) or point mutations, and they activate or enhance the tyrosine kinase function. The mutations build up resistance to small molecule tyrosine kinase inhibitors and standard induction chemotherapy. Therefore, targeting these mutations in next-generation FLT3 inhibitors has become a very attractive drug choice for several Pharma companies.

Although the FLT3 mutation is the most common AML mutation, FLT3-mutated AML is still a major challenge to treat. Patients with FLT3-mutated AML typically have a shorter remission duration and a reduced overall survival.

 

Physician Adoption and Brand Perception of Rydapt® is clearly on the Rise

LiveTrackerTM confirms the impact of the results published in the New England Journal of Medicine (NEJM) in August 2017, showing that the addition of Rydapt® to standard chemotherapy is perceived as the best alternative to prolong overall and event-free survival in patients with FLT3-mutated AML. In the study, the benefit of Rydapt® on overall and event-free survival was consistent across all FLT3-mutation subtypes, including ITD and tyrosine kinase domain (TKD) FLT3 mutations. The success of the safety and efficacy of this study may have played a large role in the continued increase in physician adoption and brand perception of Rydapt®as seen on LiveTrackerTM.

As can be seen in Figures 1 & 2, the overall brand perception of Rydapt® increased rapidly from August 2017, (pre-publication), to September 2017, (post-publication). Since then, the brand perception has continued to increase. In addition, between June 2017 and February 2018, our LiveTrackerTM showed a 45% increase in physicians adopting Rydapt® for regular use, as opposed to less than an 11% overall increase in physicians adopting similar drugs, crenolanib (Arog Pharmaceuticals, Inc.), gilteritinib, and quizartinib.

Figure 1. August 2017 Brand Perception of Midostaurin vs Other drugs.
Source, LiveTrackerTM AML (Pre NEJM Publication)

 

 

Figure 2. September 2017 Brand Perception of Midostaurin vs Other drugs.
Source, LiveTrackerTM AML (Post NEJM Publication)

 

Rydapt’s First-To-Market Advantage

The FDA approval of Rydapt® in April 2017, has shown that the first-to-market advantage can lead to success in physician adoption. Rydapt® is the first drug targeted to treat FLT3-mutated AML in combination with chemotherapy. Not only did Rydapt®  receive US FDA approval in April 2017, it also received EU approval in September 2017. Rydapt® is the first evolved drug in the treatment of newly diagnosed FLT3-mutated AML in more than 25 years.

Although this area in AML treatment is highly competitive, there is still room for innovative Pharma to fill the gap by providing therapies that can further improve the overall and event-free survival rates of patients with FLT3-mutated AML.

 

A New Angle: Could Gilteritinib be the New First-to-Market Drug for Relapsed or Refractory AML?

Recently (May 29, 2018), the US FDA accepted the priority review application for the use of gilteritinib (Astellas Oncology) in the treatment of adult patients with relapsed or refractory AML with FLT3 mutation.

Taking the unique angle of “relapsed or refractory AML” is a good strategy for Astellas as it could differentiate gilteritinib substantially from other competitor drugs for AML. There are currently no other drugs on the market that specifically target relapsed or refractory AML. The company’s goal is not only to demonstrate that gilterinitib can treat FLT3-ITD and FLT3-TKD cases, but that it can also inhibit the AXL receptor.

Figure 3. Source, LiveTrackerTM  AML – US Market Q1 2018

Adoption of gilterinitib as seen in LiveTrackerTM has remained at a baseline since May 2017, but is beginning to pick up since the FDA approval. If Astellas can find a unique way to educate physicians on the benefits of gilterinitib, they may be able to break into the market.

 

The 2018 Forecast – Emerging Drugs for the Treatment of FLT3-TKD

In addition to Rydapt®, forecasts show other new drugs projected to make an impact in 2018, including enasidenib (Idhifa® ) and CPS-351 (Vyxeos™).

As of March 2018, LiveTrackerTM showed that the level of drug awareness for Vyxeos™ was at a high of 97%, which is comparable to the 94% awareness of Rydapt® (Figure 4). From Figure 4, you can see that the physician awareness of Vyxeos™ increased by a huge leap just between January and February this year. So what factors can make physicians adopt one drug over the other? The differences in physician adoption will depend on specific uses for these drugs. For example, in a 2018 interview with OncLive, Dr. Stuart L. Goldberg indicated that his choice between Vyxeos™and Rydapt® would depend on the history of the patient, (i.e., whether the patient has secondary AML or a genetic alteration of FLT3).

 

Figure 4. Source, LiveTrackerTM AML  – US Market Q1 2018

Based on the HCPs intention to prescribe these new drugs we predict that in all 2018 Rydapt® will continue to make leaps and bounds, and Vyxeos™ will come in as a close second (Figure 5). This prediction is confirmed by the rapid increase of Rydapt®  patient share that is observed in LiveTrackerTM for Fit FLT3 patients, in particular if when are eligible to clinical trials.  

Figure 5. Source, LiveTrackerTM AML – US Market Q1 2018

 

The Need for Emerging Drugs with Unique Benefits

Emerging drugs that can focus on unmet needs, such as survival of elderly patients, which has remained the same in the last 20 to 30 years, may be able to actualize the benefits of first-to-market just like Rydapt . There are major clinical and commercial opportunities in this space.

Physicians will keep their eyes out for such emerging drugs in the 2018 pipeline. Pharma companies should focus on these types of unmet needs in order to make progress in FLT3-mutated AML treatments.

 

Background on Information Presented

The Market insights and Real World Evidence information presented in this article is derived from the analysis of 440 Hematologist’s responses and 1,530 charts from 2017 to 2018 in the US market. Medimix’ LiveTrackerTM provides physician AND patient real-time level data aggregated monthly, quarterly, or annually which helps forecast trends in Pharma.

LiveTrackerTM is available in 50 countries and across 22 Oncology and Hematology indications.

Please do not hesitate to ask us for more information on how LiveTrackerTM can improve your market intelligence with the goal of increased product sales and better patient outcomes.