“CRISPR” to change genes.. A biotechnology that will change the face of the pharmaceutical industry

Just a decade after the invention of CRISPR technology, the first drug using the revolutionary gene-editing technology will be within reach of regulators by the end of the year, promising to finally transform the treatment of genetic diseases.
In 2012, Nobel laureates Jennifer Doudna and Emmanuel Charpentier published a scientific paper proving that a key part of the bacterial immune system can be used to cut DNA, eliminating, erasing or correcting genetic errors.
Their discovery has sparked a race among startups to find transformative — and perhaps even curative — treatments that have evolved much faster than previous advances in biology.
The first company closest to success is CRISPR Therapeutics, which, in partnership with Vertex Biotechnology Group, expects to submit final stage data for approval for the treatment of the hereditary blood diseases sickle cell anemia and beta-thalassemia to regulators in the European Union to present. and the United Kingdom at the end of 2022.
His latest data shows that all patients with sickle cell disease are now symptom free and that the vast majority of beta thalassemia patients are no longer dependent on blood transfusions.
Doudna said it was “exceptional” that sickle cell patients like Victoria Gray, who was treated three years ago in the first trial, “have already been cured of the genetic disease”.
She told the Financial Times, “One of the most surprising and exciting things for me is how quickly it can be applied in the clinic. It’s been the basis for so many companies, and it’s generated tens of billions of dollars in value, thousands upon thousands job opportunities.”
As a result, major drug groups such as Pfizer, Bayer and Regeneron became interested in the cause and formed partnerships with industry leaders. Analysts expect drugmakers to soon be in the market to buy CRISPR-based drug companies, in part in hopes of acquiring the tool to improve innovative cancer treatments.
But the development of CRISPR has also raised important questions about the ethics and long-term implications of gene editing.
Many scientists have condemned a Chinese researcher who revealed in 2018 that he had edited the genetic code of two newborn twin girls. There were also intellectual property lawsuits, which discussed the contributions of Doudna and Charpentier and Feng Zhang of the Broad Institute, who wrote a paper explaining how CRISPR works in the human body.
For startups working on drugs based on CRISPR technology, a general decline in biotech stocks, some failed trials and safety concerns in the gene therapy-aligned field have made things more difficult. It is becoming increasingly difficult to convince investors that this revolution has solid power.
When the first CRISPR treatments are approved, there is the issue of persuading insurers and governments to pay the higher premiums, just as drug price reform is back on the agenda in the US, the world’s largest drug market.
Vijay Pandey, general partner at venture capital firm Andreessen Horowitz, compares CRISPR to the invention of the transistor, which revolutionized computer design.
“We’re just in the very early stages,” he said. “I think where we are now is maybe closer to the 1960s with computers.”
The biggest remaining scientific challenge is getting CRISPR to other parts of the body, other than relatively easy areas like the blood, liver and eyes. Kieran Musunoro, a gene editing specialist at the University of Pennsylvania, said the researchers are already starting to make some progress.
“This will become an extremely leading trend in the next 10 years,” he said. “The treatment will be transformative because it will greatly expand the number of diseases we can treat in patients with CRISPR.”
CRISPR’s scientific success is due in part to its ability to use or adapt technology developed and applied in gene therapy, a method of delivering missing genes to patients that has been used to treat life-threatening conditions such as spinal muscular atrophy.
It also took advantage of the vast amount of data on the human genome, which helped scientists understand which genes to target.
“The cool thing about CRISPR is that the timing was right,” Doudna said.
Scientists soon built on the original discovery. About five years ago they created the Basic Mod, which can make more subtle changes. Pfizer has partnered with basic modification company Beam Therapeutics in a deal worth up to $1.35 billion, hoping to leverage its expertise in lipid nanoparticles, which it developed from its work on a Covid-19 vaccine, to spread as a way to deliver CRISPR treatments.
While most trials still target rare diseases, base modification company Verve finally treated its first patient in a study targeting a genetic condition that causes high cholesterol, which could one day be used in a market of millions of patients.
CRISPR is also being used to advance an individually tailored type of cancer treatment called CAR-T therapy, which could tempt drug companies to acquire smaller, specialized biotech companies, according to Murray Rycroft, an analyst at Jefferies Bank.
Big drug groups have big piles of money and a number of them need to build a system of drug leads before a large number of patents expire at the end of the decade.
Antalia CEO John Leonard, which implemented the first CRISPR delivery into the body “rather than extracting, altering and returning cells” as part of its liver disease trial, said it was “essentially a given ” that every major drug company should do this. has some capabilities of CRISPR.
Not everyone is convinced. After two years of recovery during the pandemic, the entire biotech sector is suffering. Public investors are less focused on healthcare and specialists worry that many companies are going public too soon, often without any clinical data.
Last year, the Nasdaq biotech index fell 21 percent — but CRISPR companies saw further declines. Shares in Antalya fell 61 percent last year, Verve 42 percent, Editas fell 73 percent, and Beam Therapeutics and CRISPR Therapeutics each lost about 40 percent of their market capitalization.
2019 and 2020 were record-breaking for the sector, and especially for gene therapies, but now investors are starting to realize that there are still challenges ahead, says Noman Haq, managing director of life sciences and healthcare EMEA at Silicon Valley Specialized Bank.
“There’s a realism that while technology can be great and wonderful, the harsh reality of business is will I get paid for this? Will I be much better than competitors and in any particular group of patients?” he said.
The market has also been hit by many setbacks in clinical trials of gene therapies, although not specifically in treatment using CRISPR technology.
In 2020, the US Food and Drug Administration rejected a hemophilia treatment from Biomarin and requested more data, although it has since received conditional approval in the European Union. Recently, VBL’s ovarian cancer gene therapy proved no better than current standard care, while Biogen lost more than $500 million after two failed gene therapy trials.
Most worrying for some investors is that trials are being halted due to safety concerns. Last year, the Food and Drug Administration halted many trials over concerns that the treatments could increase the risk of cancer. The most famous were two experiments conducted by Bluebird Bio. One trial was resumed after one participant’s leukemia condition was found to be unrelated to the drug. But in another trial, the drug has been linked to disease, even as regulatory advisers have concluded that the drug’s benefits still outweigh the risks, and are awaiting approval to resume trials.
The CRISPR companies emphasize that their technology is very different from traditional gene therapies, which involve introducing a gene rather than changing it. John Evans, CEO of Bem Therapeutics, said you can’t always control where a gene is added in some types of gene therapy, but with CRISPR you can — and that basic modification, Bem’s area of ​​expertise, is even more subtle.
However, some scientists want to wait for more information about how CRISPR edits affect patients in the long term.
Luigi Naldini, a gene therapy pioneer at Vita Saliot San Raffaele University in Milan, said the overall outlook for CRISPR was “positive” but thought companies needed to examine the data over a longer period.
“I don’t want to be Cassandra – someone who doesn’t heed his warnings – but in gene therapy we have past experience, and follow-up data over a long period of time,” he said. “Negative genome-wide results are not immediately apparent.”
There was good news for gene therapy this week when Bluebird Bio’s treatment for beta thalassemia received FDA approval. It has a list price of $2.8 million in the United States, making it the most expensive single-dose drug ever.
Evans notes that investors appear to be distinguishing between the two areas, as shares in companies using gene therapies that rely on the common delivery method that uses lentiviral vectors have fallen significantly more than shares in CRISPR companies.
He said: “It’s like a two-sector story in medicine, between gene therapy, which is still somewhat in a downward trend for now to deal with technical and safety issues. And then gene editing, which I think is still ongoing , in fact, although fluctuations”.
Gene therapies provided the building blocks for CRISPR—but they didn’t solve the problem of how to pay for potentially curative single-dose drugs. Pharmaceutical makers argue that the higher prices — Novartis’ one-time gene therapy for SMA has a $2.1 million price tag in the U.S. — are good value because they save years of health care costs for critically ill patients.
Steve Sidhouse, an analyst at Raymond James Bank, said the industry is debating how to make higher prices more acceptable, including by spreading payments over five years, or asking for treatment only if it works. “It is not entirely clear in the long term whether a higher price per se will be acceptable,” he said.
If the treatment for sickle cell anemia is approved, likely next year, CRISPR Therapeutics will be the first to test the market for a drug using CRISPR technology. CRISPR Therapeutics CEO Samarth Kulkarni said it and Vertex should “lay the foundation for a whole new class of drugs”. “Ultimately, it will change the face of the industry,” he said.

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