The title picture comes from: Gilead’s official website, this article comes from WeChat public account: Wall Street News (ID: wallstreetcn) , edited article deletion, author: Qi month
Only a few days ago, Red Desieve took the dying United States’ first confirmed patient with new coronary pneumonia back from death in just one day. (Editor’s Note: There are many widely disputed whether Radixivir is indeed a “special effect drug”, but this drug is now being tested in Wuhan for epidemic prevention. For more details , Here are two articles for reference: ” Is there a “special effect” for new coronary pneumonia in the United States? Interview with Chinese American scientists “ and < / span> “Redesivir is free for trial of severe patients in Wuhan, what about patents?” )
This miracle instantly ignited the virus-affected people, and also brought the pharmaceutical company Gilead behind it into the sight of the general public.
Gilead is not a Nobody in the medical world, but a dark horse in the anti-virus field. Not only does it use only four medicines on its own,An initiative to eradicate hepatitis C has also made revolutionary changes in the area of anti-HIV. Now they have sounded the horn of marching into hepatitis B and are committed to the complete eradication of hepatitis B virus.
“God Medicine” Why God?
The principle is not complicated, as long as the junior high school biology is good, you can understand it.
Although Ebola virus is a filamentous virus, the new coronavirus is a coronavirus with very different appearances. It looks like a silk thread, one looks like a small ball with a crown on it, and the picture below is the indescribable appearance of coronavirus) , but they have one thing in common:
There is an RNA (RNA) polymerase.
What does this RNA polymerase do?
When the virus enters human cells, they release RNA polymerase using itself as a template. This polymerase must be present before the virus can complete the process of saving its genetic information on human DNA to infect the host.
This RNA-synthesized DNA process is called reverse transcription because it is the reverse of the transcription of human genes from DNA to RNA.
Conversely, without RNA polymerase, new coronaviruses and Ebola viruses cannot harm humans even if they enter the human body.
Reedivir takes advantage of the weakness of Ebola virus and new coronavirus. Its role is to inhibit RNA polymerase and interfere with the virus’s replication of genetic information on human DNA. In layman’s terms, this drug simply prevents the virus’s genes from successfully breeding, making it “broken off.”
Redesivir’s antiviral principle sounds very logical, but it does not cure all poisons.
Different viruses may require different antiviral drugs even if they belong to the same family. Scientists need to decode the complete genetic sequence of the virus before they can conduct targeted drug development, which is difficult. Most importantly, coronavirus is a single-stranded RNA that lacks the ability to correct during replication, so the possibility of mutation is high.
This means that the development of antiviral drugs like Redecive is actually a headache. From this perspective, the pharmaceutical companies behind it are obscure heroes.
Among these pharmaceutical companies, there is Gilead Sciences (Gilead Sciences) .
The Mother of “Magic Medicine”: Gilead
Compared to the old drug companies such as Merck and Johnson & Johnson, which are involved in multiple disease fields, the Gilead company is too specialized. Since its establishment, they have always focused on treating two types of viruses. Among the drugs, one is AIDS and the other is liver disease.
Why are these two areas? Because nearly a third of people living with HIV are also infected with the hepatitis virus.
In 1987, Michael L. Riordan, a 29-year-old graduate of Johns Hopkins University School of Medicine, founded a biomedical company in Foster City, California. But the company’s name, Oligogen, was spit out too much, so he used an ancient drug called “plant exuding aromatic fats” that is mentioned many times in the Bible. (Balm of Gilead) changed the company name to Gilead Sciences.
Michael L. Riordan was unfortunately infected with dengue fever while working in the Philippines and was killed by the virus. He has always wanted to introduce drugs to treat genetic diseases, but this drug has repeatedly failed in the laboratory. In 1996, Michael L. Riordan sadly left the throne at the helm.
From then on, John Marti, who previously worked for Bristol-Myers Squibb, became Gilead’s chief executive, hoping to use his research expertise in nucleotides to develop effective antivirals. Since then, Gilead has embarked on the golden avenue of antiviral drug leaders.
However, Gilead did not go well. It took them 9 years to get the first US drug approval. It was not until 1996 that Vistide, a drug used to treat cytomegalovirus retinitis in AIDS patients, was approved for marketing in the United States.
It’s not the hardest one yet. Gilead took a full 14 years from starting operations to achieving profitability. In 2001, the company finally turned a profit and reported a net profit of $ 52.3 million. Since then, the company has been like blindfolded in its performance.
Just look at one of Gilead’s core products and you know how hot their sales are.
SOVALDI (Sofosbuvi, scientific name: Sofosbuvi, commonly known as “Gee generation”, Chinese name: Sowardi) span> In December 2013, the company was approved for listing. The listing accounted for US $ 5.75 billion in just two quarters, and it sold US $ 10.3 billion in that year. This was a new record in the history of global new drug sales.
It’s upgraded version of HARVONI (scientific name Ledipasvir & Sofosbuvir, commonly known as “Ji II”, Leidipavir 90mg / Sofosbuvir 400mg, Chinese name Xia Fanning) was also a big hit. It went on sale in October 2014 and generated $ 2.1 billion in two months.
Gilead’s total revenue doubled that year to $ 24.9 billion. Adjusted net profit reached 133Billion US dollars, almost four times the previous year’s (2013) .
It’s not without reason to make so much money-Gilead’s medicine is very expensive. The cost of one course of treatment for the “Gill Generation” SOVALDI is $ 84,000, and the average price per capsule is more than $ 1,000. “Gyr II” HARVONI is more expensive, $ 94,500 per course.
Don’t look so expensive, but they work well. The cure rate is close to 100%. Therefore, in the first year of listing, the market demand in the United States was so hot that 140,000 patients were taking medication.
In the spring of 2017, the cumulative increase in Gilead’s stock price since its listing in 1992 successfully exceeded 17,500%. I don’t know if the “share god” Buffett regretted rejecting the company at that time.
Speaking of this, we will go back to 1988. The young Michael Riordan relies on the spirit of the newborn calf to not be afraid of tigers, and strongly invites Buffett to join the company as a director or investor.
However, Buffett finally wrote a rejection letter: “Sorry, I can’t bring anything special to your company, except my reputation.”
Where is Gilead’s “cow”?
1) “Full Plan Cocktail Therapy” in the field of anti-AIDS
In the field of HIV prevention and treatment, although Gilead is a rising star, they have achieved breakthroughs.With the “full plan cocktail therapy”, the mainstream of AIDS drugs has been changed to a single oral medication, which has rewritten the history of humans against AIDS.
Cocktail therapy is not about using cocktails to drink medicine, but to use multiple drugs at the same time, just like mixing cocktails. This is a new method proposed by Chinese scientist He Dayi in the mid-to-late 1990s.
Cocktail therapy is based on triple therapy and quadruple therapy, that is, a combination of three or more drugs. This method has good efficacy, can reduce the resistance caused by a single medication, and can prolong the life of patients. Since then, human AIDS control has begun to make a qualitative leap, and AIDS has gradually changed from a fatal disease to a manageable chronic disease.
However, cocktail therapy requires the combined use of antiviral drugs with other mechanisms. Several drugs cannot be taken at the same time, but there is a sequence of medication or a certain interval. If you do not take it as prescribed by your doctor, the treatment effect will be greatly reduced.
More importantly, if patients do not take the medicine on time, they are likely to develop resistance, making subsequent treatment more difficult. In addition, this therapy has obvious side effects and is very inconvenient, and many drugs require injection or inhalation.
In 2004, Gilead launched Truvada, the first “half plan” cocktail, which only needs to be taken with efavirenz. Two years later, Gilead successfully integrated these two medicines into a single medicine, making it a true “full plan” cocktail therapy drug, named Atripla. This triple single-piece combination reduces the patient’s medication from more than 20 capsules per day to 1 capsule per day, and has a higher virus suppression rate and less adverse reactions, making the lethal AIDS controllable.
Truvada’s AIDS Map
In the next few years, Gilead produced according to law and successively launched Stribild, Genvoya, Complera and Odefsey, and gradually “dominated” the AIDS drug market.The former occupied three quarters of the market share. These new treatment options have further strengthened Gilead’s control of HIV, and the drug resistance of patients has dropped significantly.
2) Eliminate hepatitis C
Although Gillard has successfully developed a series of AIDS drugs, he has put on the halo of anti-viral experts, but what really made this company famous and established itself as a global anti-virus giant is to cure hepatitis C. Of medicine.
Gilead’s impact on the disease is subversive.
In 2011, Gilead’s development of anti-HIV drugs slowed down, and several key component patents in compound preparations also faced expiration. Gilead, like several other rival companies, is shifting resources to hepatitis C drugs.
Before the launch of Gilead ’s hepatitis C divine medicine, the efficacy of drugs against hepatitis C virus was relatively limited, and the cure rate was only 50% -80%. Moreover, the mainstream method was injection of interferon. Its curative effect is not exact and may lead to A series of serious side effects, such as flu-like symptoms, anemia, and depression.
Gilead kicked the door hard and directly raised the cure rate to an unprecedented high: close to 100%. Almost in just three or four years, hepatitis C was almost completely eliminated by Gilead. To achieve this record feat, Gilead used only four drugs.
At the end of December 2013, Sovaldi, an anti-hepatitis C virus drug commonly known as “Gee Generation”, received FDA approval. This drug has a cure rate of more than 90% for chronic hepatitis C with genotypes 2 and 3. Moreover, it only needs to be taken orally, and interferon is not required for a large part of hepatitis C, and the whole course of treatment is only 3 months.
Sovaldi, a miracle drug, swept the market immediately after it was launched, dying out a group of hepatitis C drug competitors, and stimulated the rapid expansion of the oral drug market. In the first year of listing, Sovaldi reached the second place in the world’s best-selling drug list with tens of billions of dollars in sales, creating a myth in the history of new drug sales, and no one has broken it.
Gilead not only nearly recovered the cost of acquiring Sovaldi’s R & D enterprise in one year, but also entered the global pharmaceutical company TOP 10 club, thus becoming a well-deserved leader in the field of hepatitis C treatment.
However, Gilead did not “let the bullets fly for a while” and let Sovaldi make more money. Instead, he hit the iron while he was hot. In less than a year, he launched the “Gyr II” Harvoni. Not only does it work quickly, it also completely frees patients from interferon.
In the next few years, Gilead launched another “Gill II”, “Gill III” and “Gill IV” hepatitis C drugs, covering all six genotypes of hepatitis C virus. They can quickly block the target virus. Thus eradicating hepatitis C. This is fundamentally different from the anti-AIDS drugs that made Gilead’s fame more than a decade ago. The latter only controls infections and requires lifelong medication.
The competitors are terrible. In 2014, just one year after the launch of “Gee Generation”, Incivek, a popular hepatitis C drug jointly developed by Vertex and Johnson & Johnson, was labelled “Remarks”> (Trarevir) Announcement of delisting, Merck’s Victrelis’ current year’s revenue has shrunk sharply from 428 million US dollars to 153 million US dollars. Johnson & Johnson Olysio 2.302 billion US dollars, but also a short-lived, shrunk by 70% in 2015, only 620 million US dollars, and even only 100 million US dollars in 2016 …
However, in a few years, investors found that Gilead’s own hepatitis C drug performance has declined since 2016, and the annual revenue in 2017 fell from US $ 30.4 billion in the previous year to US $ 26.1 billion. A reduction of 40% is only $ 9.1 billion. Moreover, not theirs, the performance of the entire hepatitis C drug research and development company is declining. In 2018, the global market for direct anti-HCV drugs shrank by over 40% compared to the peak period of 2015.
It is not difficult to understand that hepatitis C is an infectious disease. When European and American patients are cured on a large scale, the market will shrink significantly and the drug will be relatively saturated, which will naturally affect Gilead. Corporate Chief Financial OfficerRobin Washington was frank at the time that new competition and declining patient numbers were the main reasons for the decline in income. He also expected that in 2018, hepatitis C drug revenue would “cut” to between $ 3.5 billion and $ 4 billion.
Due to the decline in performance, Gilead’s stock price has fallen from a high of 125 US dollars in August 2015, and has entered a long-term decline. Today it is only more than 60 US dollars.
It can be said that in terms of curing hepatitis C, Gilead perfectly interprets what it means to “take the way of others, let others have no way to go, and finally they have no way to go.”
3) Launch of the safest new hepatitis B drug in history
After subduing hepatitis C, Gilead aimed at hepatitis B again. Their goal is very clear: like killing hepatitis C, eliminating hepatitis B.
But it’s not easy. Like Hepatitis C, Hepatitis B is also a “difficult little ghost”. Hepatitis B can cause cirrhosis and is the direct cause of 80% of primary liver cancers worldwide.
It is estimated that approximately 257 million people worldwide have hepatitis B. There are about 86 million people with hepatitis B infection and about 20 million people with hepatitis B in China. The incidence is still rising, and about 300,000 people die each year from HBV-related cirrhosis.
Are there any therapeutic drugs? Yes, but but there is no functional cure, they can only suppress the virus, and patients need to take medicine for a long time. Moreover, the effect is not good, and side effects and drug resistance are easy to occur.
At present, there are mainly two types of commonly used antihepatitis B drugs on the market: immunomodulators (interferon) and direct antiviral drugs (oral nucleosides) . The two drugs each have their own shortcomings. The former has large side effects, is not taken orally, is inconvenient to use, and the latter has drug resistance.
But when Gilead took the shot, the situation changed significantly. They have launched two anti-HBV drugs, TDF (Tenofovir, Viread, Chinese name Wei Ruide) andIts upgraded version is TAF (tenofovir alafenamide fumaric acid, Vemlidy, Chinese name Weilide) . Among them, the dosage of TAF is only one-tenth of TDF.
These two drugs immediately grabbed a large part of the market and became two of the three main oral hepatitis B drugs. Both drugs are nucleoside reverse transcriptase inhibitors. They only need to be taken orally once a day, and have almost no drug resistance and few side effects.
Although TDF and TAF have not completely eliminated hepatitis B, it can effectively inhibit the replication of hepatitis B virus for a long time, thereby avoiding further deterioration of the liver, greatly reducing the incidence of cirrhosis and liver cancer, and prolonging the life of patients.
4) Medicine with consumer product thinking
Gilead’s medicine takes into account the patient’s experience in terms of convenience, dosage, efficacy, and side effects. It only pushes oral pills, and greatly reduces the dosage. The traditional therapy of multiple medicines and multiple pills in one step is directly compressed into one pill, and only one tablet is needed every day.
The triple therapy and even the quadruple cocktail therapy commonly used in Europe and America can only inhibit virus replication and cannot completely cure them, and generally have severe side effects and drug resistance. And it is not convenient to take, the commonly used interferon cannot be taken orally, usually by injection or nebulization. The treatment time for these therapies is usually about one year, with an average cure rate of 50%.
Sovaldi, a hepatitis C miracle medicine, is administered orally, and only requires one tablet per day, which is smaller than the dose of many cold medicines. Although its upgraded versions “Ji II” and “Ji III” belong to the dual therapy drugs, “Ji IV” is a triple therapy drug, but it is better to take one tablet a day. It is a compound single tablet treatment plan. Patients also don’t need genetic testing.
Gilead chose to gradually upgrade the drug for slightly different disease families, so that it can eventually treat all diseases of the same type.
This is the case of Bingtongsha, known as the “Three Generations of Kyrgyzstan.” In contrast to the “Genesis 1” Sovadi, who still needs interferon injection in the face of genotypes 1 and 4, hepatitis B can treat all six genotypes of chronic hepatitis C virus infection in adults. It is not affected by the degree of liver damage in patients, and is suitable for almost all infected patients in the clinic.
In addition, the cure rate of propicona has been further increased to 99%. The duration of treatment has also become shorter, and many patients only need to take 8 weeks instead of 12 weeks.
5) Market strategy: price tiering
To some extent, Gilead can be said to have subverted the sales tradition of the pharmaceutical industry and rewritten the rules of competition in the pharmaceutical market.
Nothing else, it is essentially a price war, with tiered pricing strategies in different countries and different markets.
Traditional medicine companies have been reluctant to reduce prices for patients in developing and poor countries for many years. However, Gilead has learned from this experience and since 2003 began to implement low-cost sales strategies in less developed countries. This approach was unsuccessful at first, and was subsequently welcomed by more and more patients in underdeveloped regions, and large pharmaceutical companies eventually had to cut prices.
In Egypt, Sovaldi, a hepatitis C elixir, sells for only $ 300 per bottle. Aiming at China’s huge population of hepatitis C patients, Gilead’s drug pricing is significantly lower than in the United States. Last year, Gilead successfully cut prices by 85% when participating in a drug negotiation. Hepatitis C drug sofosbuvir weipastatvir tablets (Protona) , Aiken, a drug for HIV-1 infection The price of the replacement film (Jie Fukang) is only 15% of that in the United States. Hepatitis B new drug propofol tenofovir tablets (Weilid) When it was launched in China in December 2018, it was priced at 1180 yuan, which is roughly equivalent to the US 20% of the price.