As we expected in our posting yesterday under Today’s Highlights, the U.S. Food and Drug Administration (FDA) approved Loxo Oncology’s (LOXO) Vitrakvi® (larotrectinib), the first oral TRK inhibitor for adult and pediatric patients with solid tumors having a neurotrophic receptor tyrosine kinase (NTRK) gene fusion. The approval is for the cancers that have no known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that has progressed following treatment.
NTRK gene fusions
NKTR gene fusions are genomic alterations that result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, which promotes cell proliferation and survival in tumor cell lines.
TRK fusions can be found in many types of solid tumors and affect both children and adults. Results from the clinical trials that led to the approval of Vitrakvi demonstrated clinical benefit across numerous unique tumor types, including lung, thyroid, melanoma, GIST, colon, soft tissue sarcoma, salivary gland, and infantile fibrosarcoma.
The Drug
Vitrakvi is a CNS active TRK inhibitor. It is the first treatment to receive a tumor-agnostic indication at the time of initial FDA approval. In clinical trials of patients with TRK fusion cancer, Vitrakvi demonstrated an overall response rate (ORR) of 75%, including a 22% complete response (CR) rate.
Adverse Effects
Vitrakvi® (larotrectinib) has warnings and precautions of neurotoxicity, hepatotoxicity and embryo-fetal toxicity. The most common adverse events observed in more than 20% of patients, regardless of attribution were: increased ALT, increased AST, anemia, fatigue, nausea, dizziness, cough, vomiting, constipation and diarrhea. The majority of adverse events occurring in greater than or equal to 10% of patients were grade 1 or 2.
Comments
David Hyman, M.D., Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and a Global Principal Investigator for a larotrectinib clinical trial said, “The FDA approval of larotrectinib marks an important milestone in how we treat cancers that have an NTRK gene fusion – a rare driver of cancer. I have seen firsthand how treatment with larotrectinib, which is designed specifically for this oncogenic driver, can deliver clinically meaningful responses in patients with TRK fusion cancer, regardless of patient age or tumor type. We now have the first therapy approved for this genomic alteration, regardless of cancer type.”
Robert LaCaze, member of the executive committee of Bayer’s Pharmaceuticals Division and head of the Oncology Strategic Business Unit at Bayer said, “Vitrakvi is the culmination of years of hard work and research by many people to bring the first-ever treatment to patients with TRK fusion cancer. TRK fusions are rare but occur across many different tumor types. In this era of precision medicine, we are delivering on Bayer’s commitment to advance the future of cancer care while providing value for patients and physicians. It is very rewarding to provide a therapy specifically for patients with advanced solid tumors harboring an NTRK gene fusion.”
Prohost Observations
We believe yesterday’s FDA decision to approve Vitrakvi says a lot about Loxo Oncology’s scientific fundamentals. The scenario of the creation, development and approval of Vitrakvialso says a lot about the capability of the Loxo/Bayer team towards providing unmet needs for condemned patients with life-threatening diseases that have yet to receive effective treatments let alone any treatment that would bring hope to hopeless humans including children and adults. These capabilities are what made us enthusiastic for this news and before us, the FDA, which granted these products accelerated approval and breakthrough designation and more.
Loxo Oncology has proven its capability and its courage at the same time. It recognized the fact that to succeed in treating TRK fusion cancer the drug might have adverse effects, yet it did not blink or retreat. Together with Bayer they also recognized that the drug’s adverse effects do not measure when compared to the life-threatening cancers with TRK fusions, which occur across many different tumor types. (Read Above)
Bayer Access Programs
Bayer’s comprehensive value and access programs enable U.S. patients to access the medication and receive the support they may need. As part of this commitment Bayer is providing two comprehensive programs: The Vitrakvi Commitment ProgramTM and the TRAK AssistTM Patient Support Program.
The Vitrakvi Commitment Program will refund the cost of Vitrakvi to payers, patients and third-party organizations paying on behalf of patients in the event eligible patients do not experience clinical benefit within 90 days of treatment initiation.
In the TRAK AssistTM Patient Support Program provides comprehensive reimbursement support and patient assistance services. For more information and eligibility requirements please call, 1-844-634-TRAK (8725).
Important to note as well is “Express Scripts applauds Bayer for its thoughtful approach to patient access. The Vitrakvi Commitment Program represents a significant advance to patient access,” said Steve Miller, M.D., Chief Medical Officer of Express Scripts. He added, “We look forward to working together to help those who will benefit from this medicine have affordable access to it.”
Investors’ reaction to the news: Investors decided to sell the stock on good news as usual. They hid behind the adverse effects and the black box, not fathoming the fact that the FDA reviewed Vitrakvi under Priority Review, which is reserved for medicines that could provide significant improvements in the safety or effectiveness of the treatment for serious conditions.
Prohost Prediction: The stock selloff is temporary and will, sooner rather than later, transform into a stock rally. Prohost’s speculation is based on the firm’s technological capabilities and its creative pipeline, which represents a typical pipeline that usually attracts deep-pocketed ambitious firms.
A lot of events that went unrecognized, as well as others that we expect will occur in the near future, will be posted in the next Prohost Letter, coming soon.
News & Comments
November 27, 2018
Loxo Oncology product Vitrakvi® has been granted FDA approval. The real meaning of the approval
As we expected in our posting yesterday under Today’s Highlights, the U.S. Food and Drug Administration (FDA) approved Loxo Oncology’s (LOXO) Vitrakvi® (larotrectinib), the first oral TRK inhibitor for adult and pediatric patients with solid tumors having a neurotrophic receptor tyrosine kinase (NTRK) gene fusion. The approval is for the cancers that have no known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that has progressed following treatment.
NTRK gene fusions
NKTR gene fusions are genomic alterations that result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, which promotes cell proliferation and survival in tumor cell lines.
TRK fusions can be found in many types of solid tumors and affect both children and adults. Results from the clinical trials that led to the approval of Vitrakvi demonstrated clinical benefit across numerous unique tumor types, including lung, thyroid, melanoma, GIST, colon, soft tissue sarcoma, salivary gland, and infantile fibrosarcoma.
The Drug
Vitrakvi is a CNS active TRK inhibitor. It is the first treatment to receive a tumor-agnostic indication at the time of initial FDA approval. In clinical trials of patients with TRK fusion cancer, Vitrakvi demonstrated an overall response rate (ORR) of 75%, including a 22% complete response (CR) rate.
Adverse Effects
Vitrakvi® (larotrectinib) has warnings and precautions of neurotoxicity, hepatotoxicity and embryo-fetal toxicity. The most common adverse events observed in more than 20% of patients, regardless of attribution were: increased ALT, increased AST, anemia, fatigue, nausea, dizziness, cough, vomiting, constipation and diarrhea. The majority of adverse events occurring in greater than or equal to 10% of patients were grade 1 or 2.
Comments
David Hyman, M.D., Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and a Global Principal Investigator for a larotrectinib clinical trial said, “The FDA approval of larotrectinib marks an important milestone in how we treat cancers that have an NTRK gene fusion – a rare driver of cancer. I have seen firsthand how treatment with larotrectinib, which is designed specifically for this oncogenic driver, can deliver clinically meaningful responses in patients with TRK fusion cancer, regardless of patient age or tumor type. We now have the first therapy approved for this genomic alteration, regardless of cancer type.”
Robert LaCaze, member of the executive committee of Bayer’s Pharmaceuticals Division and head of the Oncology Strategic Business Unit at Bayer said, “Vitrakvi is the culmination of years of hard work and research by many people to bring the first-ever treatment to patients with TRK fusion cancer. TRK fusions are rare but occur across many different tumor types. In this era of precision medicine, we are delivering on Bayer’s commitment to advance the future of cancer care while providing value for patients and physicians. It is very rewarding to provide a therapy specifically for patients with advanced solid tumors harboring an NTRK gene fusion.”
Prohost Observations
We believe yesterday’s FDA decision to approve Vitrakvi says a lot about Loxo Oncology’s scientific fundamentals. The scenario of the creation, development and approval of Vitrakvialso says a lot about the capability of the Loxo/Bayer team towards providing unmet needs for condemned patients with life-threatening diseases that have yet to receive effective treatments let alone any treatment that would bring hope to hopeless humans including children and adults. These capabilities are what made us enthusiastic for this news and before us, the FDA, which granted these products accelerated approval and breakthrough designation and more.
Loxo Oncology has proven its capability and its courage at the same time. It recognized the fact that to succeed in treating TRK fusion cancer the drug might have adverse effects, yet it did not blink or retreat. Together with Bayer they also recognized that the drug’s adverse effects do not measure when compared to the life-threatening cancers with TRK fusions, which occur across many different tumor types. (Read Above)
Bayer Access Programs
Bayer’s comprehensive value and access programs enable U.S. patients to access the medication and receive the support they may need. As part of this commitment Bayer is providing two comprehensive programs: The Vitrakvi Commitment ProgramTM and the TRAK AssistTM Patient Support Program.
The Vitrakvi Commitment Program will refund the cost of Vitrakvi to payers, patients and third-party organizations paying on behalf of patients in the event eligible patients do not experience clinical benefit within 90 days of treatment initiation.
In the TRAK AssistTM Patient Support Program provides comprehensive reimbursement support and patient assistance services. For more information and eligibility requirements please call, 1-844-634-TRAK (8725).
Important to note as well is “Express Scripts applauds Bayer for its thoughtful approach to patient access. The Vitrakvi Commitment Program represents a significant advance to patient access,” said Steve Miller, M.D., Chief Medical Officer of Express Scripts. He added, “We look forward to working together to help those who will benefit from this medicine have affordable access to it.”
Investors’ reaction to the news: Investors decided to sell the stock on good news as usual. They hid behind the adverse effects and the black box, not fathoming the fact that the FDA reviewed Vitrakvi under Priority Review, which is reserved for medicines that could provide significant improvements in the safety or effectiveness of the treatment for serious conditions.
Prohost Prediction: The stock selloff is temporary and will, sooner rather than later, transform into a stock rally. Prohost’s speculation is based on the firm’s technological capabilities and its creative pipeline, which represents a typical pipeline that usually attracts deep-pocketed ambitious firms.
A lot of events that went unrecognized, as well as others that we expect will occur in the near future, will be posted in the next Prohost Letter, coming soon.
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