If chemotherapy is a hammer in treating cancer, then precision medicine is a laser.
Three biotech companies are leading the charge in precision medicine, an emerging experiment in oncology, says JMP Securities analyst Konstantinos Aprilakis. Loxo Oncology (LOXO), Blueprint Medicines (BPMC) and Deciphera (DCPH) all aim to shrink solid tumors by targeting a single genetic mutation in cancer cells.
Ultimately, their success could change the face of cancer treatments for a select group of patients — hitting cancer not where it occurs in the human body, but how. Aprilakis says their work could help push momentum toward very specific and targeted cancer treatments.
“This is the promise of cancer therapy that I’ve heard since before I was in medical school,” Aprilakis told Investor’s Business Daily. “As physicians we were supposed to develop a treatment regimen specific to the patient.”
Using The Human Genome
The theory isn’t new. It lies in a better understanding of efforts to map the entire human genome, the complete set of DNA in an organism. Now that the cost of a genome map is more reasonable — the first one in 1990 went for $2.7 billion; now it’s around $1,000 apiece — it’s easier to help fight cancer.
According to the National Cancer Institute, in normal cells the genome is packed with two sets of chromosomes comprised of genetic lettering. Cancer cells also have their own genomes where small alterations in those letters change the story.
“By studying the cancer genome, scientists can discover what letter changes are causing a cell to become cancer,” according to the National Cancer Institute. That’s where Loxo, Blueprint and Deciphera come in. They’re working on oncology drugs for cancers caused by single genetic aberrations.
Single genetic mutations are the culprits in just a small fraction of cancers. But for these patients, the results in clinical studies have been incredible, analysts say. They turn an old-school theory in oncology on its head, said Deciphera Chief Executive Michael Taylor.
“Cancer, typically, until recently was always identified by where it occurs,” he said in an interview. “There are many different forms of lung cancer or skin cancer.”
Aberrations In Cancer
The research is in its infancy. None of the three biotech companies have sales from approved drugs. Blueprint and Loxo reported $954 million and $38.4 million, respectively, in collaboration revenue during the first quarter. For the same period, Deciphera had no sales. None have had a profitable quarter.
All three biotech companies are researching what are known as kinases. Kinases are important enzymes in the body. But at times genetic aberrations can cause kinases to act outside their normal functions and cause cancer. Drugs from these biotech companies look for the genetic aberrations to find the cancer.
This makes for highly specific cancer treatments, Loxo Chief Executive Josh Bilenker said.
“An old school of thought, 10-15 years ago, was a lot of people said ‘Make one drug for everything,’ ” he said. “The problem is, it does a little of everything, but it does nothing well. The totality of that is not a great drug. Instead, we make built-for-purpose, single-use agents and combine them.”
Precision medicine is not a panacea in oncology, Blueprint Chief Medical Officer Andy Boral told IBD. Like Bilenker, he expects the ultimate answer in oncology to lie in combinations of medicine. Cancer itself often mutates or results from multiple mutations.
Bilenker and Boral say their biotech companies are developing libraries of precision medicine drugs that will each work on different mutations in cancer.
Targeting Lung, Thyroid Cancers
Loxo and Blueprint are working on drugs that inhibit aberrations in what is called the RET gene, which controls various functions in the body. Loxo’s Bilenker estimates RET aberrations drive 2% of non small-cell lung cancers, 10%-20% of common thyroid cancers and 60% of medullary thyroid cancer.
Deciphera — which went public last September — and Blueprint are working on cancer treatments for tumors associated with aberrations in sister genes called KIT and PDGFRA.
Loxo is nearing approval for a treatment that focuses on mutations in the TRK gene. U.S. officials will consider approving that drug in November. The firm is also working on a follow-up to that treatment. Blueprint also has a slew of other kinase inhibitors and a drug in development for liver cancer.
During the American Society of Clinical Oncology annual meeting in June, Loxo said its therapy shrank tumors in 77% of patients with RET fusion-positive cancers. In total, 45% of patients with RET-mutated medullary thyroid cancer responded to treatment.
Blueprint released the results of a study of its competing drug in April. Initially, half of patients with RET-altered non small-cell lung cancer responded. The drug shrank tumors in 40% of patients with RET-altered medullary thyroid cancer.
It’s important to note that both drugs have, so far, had minimal side effects. The goal of precision therapy is to only block what the drugs tell them to obstruct. Accidentally inhibiting other kinase can cause a number of unintended side effects, also known as off-target effects.
Blueprint is ahead of Deciphera in testing its KIT and PDGFRA drug in a rare stomach cancer known as GIST. Blueprint also is looking at it as a treatment for advanced systemic mastocytosis, a cancer of the blood and soft tissue.
In June, Blueprint said 83% of patients with advanced systemic mastocytosis responded to treatment. However, Piper Jaffray analyst Christopher Raymond noted more than half of all patients, 54%, experienced at least one severe side effect.
Meanwhile, Deciphera also has a precision medicine drug that could potentially treat GIST and systemic mastocytosis. Deciphera is now working on a Phase 1 study in advanced systemic mastocytosis, but so far doesn’t have human data to back it up for that use.
Last month, Deciphera said the drug shrank tumors in 15% of patients with GIST when the cancer didn’t respond to prior therapies. That was in line with responses from Blueprint’s drug, Raymond said. But, he noted, Deciphera’s drug resulted in fewer cases of nausea, fatigue, swelling and anemia.
Changing Oncology Drugs
Loxo’s Bilenker noted the concept of precision medicine targeting kinase is still in the early stages. Pioneers include Novartis‘ (NVS) drug called Gleevec. There’s also Sutent and Xalkori from Dow Jones component Pfizer (PFE) and Iressa from AstraZeneca (AZN).
But these biotech companies say their precision medicine drugs are just the first steps in creating a platform to develop kinase inhibitors. The goal is to provide cleaner oncology drugs than chemotherapy. Deciphera’s Taylor described chemo as “a blunt instrument” with “horrendous side effects.”
As it stands, Europe is at the forefront of a push for genotyping in cancer patients, Deciphera’s Taylor said. That allows physicians to match patients with cancer treatments tailored to the specific genetics of their tumors. The U.S. still lags in that regard.
Genotyping could help identify patients who could benefit from drugs like Deciphera’s, he said.
“When you find those patients, the response rates are really good,” he said. “They would be almost untreatable with other therapies. That’s what’s really driving (precision medicine). So patients aren’t exposed to medicines that don’t work and are more likely to get a drug that fits their particular need.”
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