"Only 2 injections a year and 100% infection prevention", Gilead's long-acting therapy has exploded in the field of anti-HIV.
On June 20, Gilead announced that topline results from an interim analysis of the pivotal Phase III PURPOSE 1 clinical trial showed that twice-yearly lenacapavir (lenacapavir) showed 100% effectiveness in preventing HIV infection in women.
This is the first milestone prevention therapy in the field of anti-HIV therapy, and Lenacapavir may become a disruptive new drug, with peak global sales of $3 billion to $4 billion. In the two trading days after the announcement, Gilead's stock price rose nearly 12%, reaching a total market capitalization of nearly $90 billion.
Although not long ago, Gilead announced at the 2024 EHA conference that the phase III study of the CD47 monoclonal antibody magrolimab had failed, resulting in a $4.9 billion loss and closing a door, with the positive results of the phase III trial of Lenacapavir, the god of fate has opened another window for Gilead.
On the other hand, the "second growth curve" tumor sector is gaining momentum, can Gilead successfully counterattack?
01
Potentially disruptive new drugs
With the announcement of positive results from Gilead's pivotal Phase III PURPOSE 1 clinical trial of Lenacapavir, there have been a variety of "five-star reviews" in the market.
Some people believe that this is the first milestone in the field of anti-HIV prevention therapy, others believe that the frequency of Lenacapavir injections of only two shots a year is close to that of the vaccine, and some even give a higher evaluation: Lenacapavir will be the "AIDS ender".
More than 5,300 women and adolescent girls aged 16-25 years were studied in the PURPOSE 1 trial from 25 locations in South Africa and 3 locations in Uganda. The participants were divided into three groups and treated with Lenacapavir (subcutaneous injections twice a year), Truvada (oral daily), and Descovy (oral daily).
Among them, lenacapavir is a "first-in-class" long-acting HIV capsid inhibitor; Truvada (Truvada, Emtricitabine/Tenofovine) is a first-generation pre-exposure prophylaxis (PrEP) drug developed by Gilead and approved by the FDA in 2004 for the treatment of people living with HIV; Descovy (Dacova, Emtricitabine/Tenofovir Alafenol) is a second-generation PrEP drug that was approved by the FDA in 2016 for the treatment of HIV as an upgraded version of Truvada at a lower dose.
Both of these PrEP drugs are the "blockbusters" of Gilead's AIDS segment. Among them, Truvada's sales exceeded $1 billion as early as 2016; In 2023, Descovy's sales reached $1.895 billion.
PURPOSE 1试验,正是头对头评估Lenacapavir对照Descovy或Truvada用于PrEP的安全性和有效性。
According to clinical results, among 2134 women in the Lenacapavir group, there were 0 cases of HIV infection; This compares to 16 events in 1068 women in the Truvada group and 39 events in 2136 women in the Descovy group. Lenacapavir not only outperformed the primary comparators HIV background incidence (bHIV) and Truvada (secondary control) while meeting both the primary and secondary endpoints, but was generally well tolerated with no significant or novel safety concerns identified.
Merdad Parsey, Chief Medical Officer at Gilead Sciences, said, "The twice-yearly treatment of Lenacapavir has demonstrated its potential as an important new tool for the prevention of HIV infection with zero infection rate and 100% efficacy. ”
Despite its inherently long-acting nature, it's no wonder that Gilead is thinking of a "vaccine" because it's given as often as it is injected close to some vaccines and has shown 100% efficacy, which is much higher than any HIV trial vaccine.
Of course, calling it a "vaccine" is just a metaphor. But the deeper meaning of this metaphor is that it points to a profound change in the field of HIV fighting.
After all, this is the first phase III clinical trial of HIV prevention with zero infection disclosed in the history of human anti-"HIV", and Lenacapavir only needs 2 injections a year, which is a milestone new breakthrough with great compliance advantages.
02
"Everyone is happy" in the field of HIV drugs?
"The road is long, I will go up and down and seek." Since the first case of AIDS was reported in 1981, humanity has been battling AIDS for 43 years.
In the 43-year history of fighting "HIV", global pharmaceutical companies have been confused, helpless, and failed, and have ushered in the dawn of success.
You must know that up to now, there is still no vaccine that can prevent HIV infection in the world, and no matter what kind of vaccine technology route has failed, hundreds of billions of research and development costs have been wasted.
In contrast, although the research and development of anti-HIV drugs has had its ups and downs, it has also made many breakthroughs in recent years. Among them, oral HIV drugs are gradually changing from once a day to once a week.
In April, Gilead and Merck announced updated results from a Phase II clinical trial of islatravir and lenacapavir, an oral combination therapy for long-acting HIV, which maintained a high rate (94.2%) of HIV patients with viral suppression (50 copies of HIV-1 RNA <per mL) at 24 weeks, with the potential to become the world's first once-weekly oral HIV drug.
In terms of injectable dosage forms, GlaxoSmithKline (GSK)'s Cabenuva, the world's first long-acting injectable therapy for HIV, can be treated once a month or every two months, and was first approved for marketing in 2020.
With breakthrough advantages, Cabenuva's sales in 2022 and 2023 will reach 340 million pounds and 708 million pounds (about 894 million US dollars) respectively, a year-on-year increase of more than 100%. And, due to the strong performance of drug sales, GSK has raised its 2026 HIV sales forecast from £6.4 billion to £7 billion.
Cabenuva's strong sales performance is a testament to the commercial value of long-acting HIV therapies.
By contrast, Gilead's Lenacapavir not only has a greater compliance advantage than Cabenuva, but its PURPOSE program includes five HIV prevention trials around the world, making it the most comprehensive and diverse HIV prevention trial ever conducted.
The aforementioned PURPOSE 1 trial is just the first batch of data, and the results of another pivotal trial, PURPOSE 2, will be announced by Gilead later this year or early 2025. The trial, conducted in several countries, including Argentina, Brazil and the United States, evaluated the effectiveness of lenacapavir for the prevention of HIV infection in men and women with different sexual orientations.
If the results of the PURPOSE 2 trial are positive, Gilead will submit a marketing application to the FDA based on data from these two pivotal trials. If nothing else, Lenacapavir may be approved for marketing by the end of 2025.
Given the impressive clinical efficacy and compliance benefits, the market is looking forward to Lenacapavir. Overseas analysts believe that Lenacapavir's global peak sales will reach $3 billion to $4 billion.
Such an optimistic forecast also stems from the vast space of the HIV drug market, especially Gilead's strong strength in the field of antiviral drugs.
In 2023, Gilead will achieve total revenue of US$27.116 billion, a slight year-on-year decline, but nearly 10 AIDS product portfolios such as Biktarvy, Descovy, and Genvoya will contribute a total of US$18.715 billion in revenue, a year-on-year increase of 6%, accounting for about 70% of total revenue.
What's more, Gilead accounts for half of the global AIDS drug market. If Lenacapavir can go public, it will undoubtedly help boost the company's performance.
03
The anti-tumor sector is in urgent need of an outbreak
Compared with the "happy for all" in the field of AIDS drugs, Gilead's gamble of more than $25 billion in the field of oncology in the past five years has yielded little success.
For example, in 2020, Gilead spent $21 billion to acquire Trodelvy, the world's first Trop2 ADC drug won by Immunomedics, which has not yet achieved a big explosion; The successive failures of the CD47 monoclonal antibody Magrolimab in the study of hematological tumors have damaged Gilead's vitality.
However, Gilead does not believe in tears and will not let go of the huge market cake in the field of oncology.
At present, Trodelvy (gosatuzumab) has been approved for 3 indications worldwide, with sales of US$680 million and US$1.06 billion in 2022 and 2023, respectively, a year-on-year increase of 79% and 56%, which is remarkable.
In addition, Trodelvy is also expanding new indications and has conducted more than 30 clinical trials, covering multiple cancer types such as lung cancer, head and neck cancer, among which 6 clinical trials of Trodelvy in combination with K drug are being carried out, involving multiple indications such as breast cancer and non-small cell lung cancer.
In addition to ADC drugs, Gilead is also accelerating the deployment of other oncology drugs.
At the end of 2022, Gilead acquired Tmunity, a next-generation CAR-T therapeutic, through its subsidiary Kite, and in May last year, it acquired XinThera for nearly $1 billion, acquiring the latter's early-stage pipeline assets of PARP1 small molecule inhibitors for oncology and MK2 small molecule inhibitors for inflammation & immunology.
In January, Gilead invested an additional $320 million in Arcus, increasing its stake to 33% and reprioritizing the TIGIT monoclonal antibody domvanalimab co-development program with a focus on advancing the Phase III clinical studies STAR-121 (lung cancer) and STAR-221 (gastrointestinal cancer).
Back in May 2020, Gilead entered into a 10-year strategic oncology collaboration with Arcus to jointly develop and commercialize the latter's innovative PD-1 inhibitor and TIGIT inhibitor pipeline, with a potential transaction value of US$2 billion. In May last year, the two companies expanded their partnership to include oncology to include inflammatory diseases.
In addition, Gilead also invested more than $1.5 billion in March 2024 to enter into a partnership with Merus to co-develop trispecific antibodies targeting novel tumor-associated antigens (TAAs).
It can be seen that Gilead is continuing to deepen its oncology treatment layout through diversified drug research and development and strategic cooperation, in order to pursue greater market returns.
04
epilogue
Perhaps the god of fate is not far away, and although the loss of CD47 monoclonal antibody has closed a door for Gilead, it has opened another window for long-acting HIV therapy.
In addition, the anti-tumor sector, which is making efforts, may become the "second growth curve" that contributes to performance in the future. This also allowed Gilead's counterattack to add a lot of chips to success.
Resources:
1. Gilead Sciences' financial reports, announcements, and official WeChat
2. "Two injections a year, 100% effective!" After 40 years of fighting "HIV", mankind will finally meet the "inflection point"", 21 New Health, 2024-06-21
3. "$320 million! Gilead Invests in Arcus to Collaborate on TIGIT Combination Therapy", PharmaCube Pro, 2024-01-31
4. Ping An Securities and Zheshang Securities Research Report