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Ground-breaking Cancer Drug Gets FDA Approval

November 28, 2018 | Expert Insights

The US Food and Drug Administration approved Vitrakvi, an advanced cancer treatment drug shown to significantly reduce tumours in 81 per cent of patients with 24 different types of cancers while causing only mild side effects.

Background

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body and is fundamentally a disease of tissue growth regulation. In order for a normal cell to transform into a cancer cell, the genes that regulate cell growth and differentiation must be altered.

A neurotrophic tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an on or off switch in many cellular functions. Tyrosine kinases are a subclass of protein kinase. Protein kinases can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer.

TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signalling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless of where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumours with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).

TRK fusion cancer is diagnosed through the identification of NTRK gene fusions using specific tests, including those that employ next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH).

Analysis

On 26 November, the US Food and Drug Administration (FDA) approved an advanced cancer treatment drug that combats solid tumours caused by a rare genetic mutation. The drug will be sold under the brand name Vitrakvi in a partnership between US-based pharmaceutical company Loxo Oncology and Germany's Bayer.

Vitrakvi, commonly known as larotrectinib, works by targeting a biomarker, or a gene that identifies a disease. This enables the drug to work across different types of tumours rather than the location in the body where a tumour started. The mutation that Vitrakvi targets is called neurotrophic tyrosine kinase, or TRK, and is a gene fusion found in solid tumours. Around 1 per cent of solid tumour cancer patients are affected by TRK fusion every year.

In clinical trials, Vitrakvi was shown to significantly reduce tumours in 81 per cent of patients with 24 different types of cancers while causing only mild side effects. Until 26 November, there had been no treatment for cancers with the TRK gene mutation. The approval of Vitrakvi means that certain types of highly advanced solid tumours that are metastatic (spreading), unable to be surgically removed and do not qualify for other treatments can now be effectively treated. It is the first commercial medicine for Loxo, a Connecticut company that develops treatments for genomically defined cancers.

Bayer plans to talk with players about expanding routine testing for cancer mutations among more cancer patients so that those who could benefit from the new drug can be identified, Reuters reported. Loxo plans to continue developing more cancer drugs based on gene mutation.

Counterpoint

Vitrakvi received an "accelerated approval" from the FDA based on the previous clinical trials. However, further clinical trials are needed to confirm the drug's benefit. The FDA said the sponsor is planning to conduct such studies.

Vitrakvi has warnings and precautions of neurotoxicity, hepatotoxicity and embryo-fetal toxicity. The most common adverse events observed in more than 20 per cent of patients, regardless of attribution, were increased ALT, increased AST, anaemia, fatigue, nausea, dizziness, cough, and similar effects. Among the 176 patients who received Vitrakvi neurologic adverse reactions of any grade occurred in 53% of patients.

Assessment

Our assessment is that the approval of Vitrakvi marks another step in an important shift toward treating cancers based on their tumour genetics rather than their site of origin in the body. We believe Vitrakvi reflects a development in cancer treatment drugs moving away from body location-specific medicine to treatments based on genetic defects and mutations.