The biopharmaceutical industry is at a crossroads at the beginning of 2023, and this industry is coming out of the most difficult time in recent years.
In 2022, the global biopharmaceutical industry has experienced many setbacks and also achieved some results. Three gene therapies targeting genetic diseases have been approved by the FDA, boosting the industry's confidence in gene therapy. Lecanemab, a new Alzheimer's disease (AD) drug jointly developed by Eisai and Biogen was successful in phase III clinical trials and was approved by FDA in early 2023. A number of small biotech companies have achieved success in clinical trials for indications such as schizophrenia, nonalcoholic steatohepatitis and ulcerative colitis, and their stock prices have soared. M&A activity has also increased over time.
Recently, the biopharmaceutical industry media BioPharma Dive has released a list of 10 noteworthy clinical trials for the first half of 2023. These trials involve phases from Phase I to Phase III, covering the first-in -class or best-in-class new drugs. Some of these new drugs are the most competitive markets and indications in the industry, such as obesity and cancer. Some of the diseases targeted may usher in a Big Year, such as Alzheimer's disease.
1. Breakthrough of Alzheimer's Disease (AD) Drugs
On January 6, the FDA accelerated the approval of Biogen/Eisai's lecanemab (Leqembi) marketing application for the treatment of Alzheimer's disease (AD). This indicates that the AD market, which has been quiet for many years, is ushering in a promising development.
This approval is based on the results of the Phase IIb proof-of-concept clinical study, in which the degree of amyloid-β (Aβ) plaque reduction and the correlation with the impact on clinical endpoints further support Aβ as a surrogate endpoint that can reasonably predict clinical benefit . In a phase III clinical trial updated in 2022, lecanemab slowed the progression of AD in early-stage patients by 27% within 18 months, which is a rare positive result among many failed clinical trials in AD.
However, just as the industry was about to turn to Eli Lilly's competing product donanemab, on January 19, news came that the FDA had issued a complete response letter. Although the reason for the FDA's refusal to accelerate approval is that the clinical data samples did not meet the requirements of 100 cases, the failure of the Aβ theory has been a precedent.
In June 2021, Biogen and Eisai introduced aducanumab (Aduhelm) to the US market. However, subsequently, this historic breakthrough product of more than 20 years encountered restrictions on its use, poor sales. Affected by this, AD track once fell into the trough.
Over the past year, Roche has suffered from the losses of Aβ theory, and the two products under research, crenezumab and ganteneruma, failed to reach the end point. Roche decided to give up, but Eli Lilly decided to continue.
Supplemental data for donanemab are expected in the second quarter of 2023, according to the FDA's complete response letter. By then, donanemab may be expected to become the third Aβ monoclonal antibody for the treatment of AD after Aduhelm and Leqembi.
2. Anti-obesity Becomes The Focus
In addition to AD, some pharmaceutical companies are also turning their attention to less controversial markets, such as obesity treatments. Many anti-obesity drugs have come into being.
Obesity affects about 650 million people worldwide and is linked to health problems such as heart disease, stroke, kidney disease and high blood pressure. Less than 1 percent of the estimated 71 million obese adults in the United States took weight-loss pills between 2012 and 2016, according to a report from the Government Accountability Office (GAO).
Pharmaceutical companies are not without effort. In the last century, drugs such as amphetamines, thyroid hormones, dinitrophenol and various combinations came to the fore, only to be pulled from the market shortly after regulatory approval because of serious side effects.
In recent years, the problem has improved. Novo Nordisk's diabetes drug semaglutide (Wegovy) was approved by the FDA in 2021 to reduce weight in obese patients.
In 2022, tirzepatide (Mounjaro), developed by Eli Lilly, was approved to treat type 2 diabetes. The drug has shown great potential to promote weight loss in overweight patients, and data from phase III trials will be available later in 2023. If all goes well, Mounjaro could soon be approved for a new indication, as the FDA has granted Eli Lilly fast-track designation to speed up the drug's regulatory approval process.
Drugs that can treat obesity are on the way. Amgen is planning to launch a mid-stage trial of a competing weight-loss drug this year, with a phase III trial expected in 2024. Not long ago, Amgen announced the amazing phase I clinical data of AMG133 - a 14.5% weight loss in 3 months.
Morgan Stanley analyst Mark Purcell said that under conservative pricing assumptions, global sales of obesity-related products could exceed $50 billion by 2030. That would lift obesity from a $2.4 billion category to one of the top 12 spending treatment areas in the world.
According to public information, Novo Nordisk and Eli Lilly will occupy about 40% of the market share, and latecomers such as Amgen, Altimmune, Zealand Pharma, Hanmi, Regor Therapeutics, Sciwind Biosciences and vTv Therapeutics also join.
According to public information, Huadong Medicine’s liraglutide obesity indication is expected to be approved in the third quarter of 2023, becoming the first liraglutide weight loss product in China.
3. The Bumps In The New Tumor Track
Interest in oncology has always been a lively biotech trend. Some drugs have achieved game-changer success in the past year, such as Enhertu, developed by AstraZeneca and Daiichi Sankyo. This ADC was first approved by the FDA in 2019 for the second-line treatment of HER2-positive metastatic breast cancer. By August 2022, the FDA had completed a marketing review in just 11 days, making Enhertu the first targeted drug to be approved for use in patients with low HER2 expression.
On 26 January, Enhertu was approved in the European Union for use in patients with low HER2 expression. Relevant indications are also expected to be approved in China in the near future. Last year, the NMPA accepted two marketing applications for Enhertu, including the treatment of low expression of HER2.
CAR-T (Chimeric Antigen Receptor T-Cell ) therapy is also promising. Carvykti, developed by Legend Biotech/Johnson & Johnson was first approved by the FDA in 2022 to treat patients with advanced relapsed or refractory multiple myeloma. Meanwhile, Breyanzi and Yescarta, two CAR-T therapies already approved for advanced cancer, have been approved by the FDA for early-stage cancer, benefiting more patients.
Continued advances in CAR-T therapies are prompting a massive increase in investment in startups in the field.
4. Gene therapy opens up the market
In 2022, some key "firsts" passed the final regulatory hurdles in Europe: in August, Roctavian became the first gene therapy for hemophilia A to be approved in the EU; In December, Europe's first Hemophilia B gene therapy was on the way, following the approval of Hemgenix by the CHMP. Also in December, the first "off-the-shelf" T-cell immunotherapy, Ebvallo, was launched in Europe.
In the American market, gene therapy has also made many breakthroughs. The FDA approved Hemgenix ahead of the EMA, with a price tag of up to $3.5 million. The world's most expensive drugs are Bluebird Bio's two products Zynteglo and Skysona, both of which have landed in the US market.
In 2023, the FDA may also approve Roctavian, the allogeneic stem cell transplant therapy Omidubicel and SRP-9001. Among them, SRP-9001 is expected to be the first gene therapy for the rare disease Duchenne muscular dystrophy (DMD), and patient advocacy groups have put a lot of pressure on the FDA to approve the therapy as soon as possible because DMD is irreversible, and SRP- 9001 can only prevent further deterioration of the condition.
However, such a breakthrough would still face pricing difficulties. Alex Cogut, director of healthcare equity research at Bryan Garnier, also expressed curiosity about these quasi-commercial treatments that come with an aura of sky-high prices.
The biopharmaceutical industry argues that high prices are necessary to cover the cost of developing gene therapies. Typically, a gene therapy costs $5 billion to develop, about five times as much as conventional drugs. The market for these drugs is also often small, and complex manufacturing and regulatory processes often result in long lead times before treatments are available on the market.
There is also a gene-edited cell therapy for sickle cell disease and β thalassemia called exa-cel. Developers Vertex and CRISPR Therapeutics aim to complete an approval application for the therapy in early 2023.
5. Drug Encounter Price "Ceiling"
If gene therapy faces pricing decisions due to its own characteristics, then the shift in regulation will cause more conventional drugs to encounter price ceilings in 2023.
In August 2022, the United States passed the Inflation Reduction Act (IRA). The bill seeks to reduce the federal deficit by reducing the price of prescription drugs.
Specifically, the bill gives Medicare the power to negotiate prices for certain drugs that lack competition, while also constraining drugmakers on Medicare's list who raise prices faster than inflation.
Starting in 2023, Medicare will be able to negotiate price with pharmaceutical companies annually for no more than 10 original drugs in Medicare Part-B and Part-D that have the highest total Medicare expenditure, have been on the market for more than 9 years (small molecule drugs) or 12 years (biological drugs), and do not have generic or biosimilar drugs.
As early as November last year, AstraZeneca CEO Pascal Soriot said through an investor conference call that unless there are large enough indications, AstraZeneca may not launch new anti-cancer drugs in the United States. Keytruda is now halfway through the patent period, but many studies on this project are still ongoing. Rob Davis, chief executive of Merck, said that he does not know whether the unfinished project will be completed in the future, nor whether he will continue to invest in subsequent indications.
Some people believe that the introduction of IRA will have a huge impact on the global innovative drug market, especially for Chinese innovative pharmaceutical companies that are undergoing globalization. However, what IRA considers more is to meet the needs of patients for medication and reduce the part of self-payment, which is difficult to compare with the control of expenses in the Chinese market.
6. Biotech Trend To M&A Deals
Biotech stock markets was lacklustre in 2022. For example, the S&P Biotech Index (XBI), which measures small and mid-cap biotech companies, is trading 50% below its last peak in early 2021.
When the market is not good, large pharmaceutical companies often compete for cheap targets and set off a frenzy of mergers and acquisitions when the market value is suppressed. However, this did not materialize in 2022. In the past year, there were not many mergers and acquisitions by pharmaceutical companies, and the largest case was Horizon, which was finally acquired by Amgen for US$27.8 billion at the end of last year. According to statistics, the amount of financing in the first three quarters of 2022 did not even reach 50% of that in 2021.
In 2023, the trend in biotech is likely to be in the direction of M&A deals. In January, the JPMorgan conference kicked off with the announcement of several M&A deals: AstraZeneca bought CinCor Pharma for about $1.8 billion, and Ipsen bought Albireo for $952 million. And Merck, which made an offer at the end of last year, has now completed the acquisition of Imago BioSciences for US$1.35 billion.
According to Evaluate Pharma, the global total of branded prescription drugs at risk of patent expiration is increasing, from $16 billion today to nearly $28 billion by 2026. In other words, the revenue of large pharmaceutical companies will be severely eroded with the arrival of the patent cliff, and "buying products" has become a shortcut.
But in addition to the acquisition of Biotech with marketed drugs, Cogut predicts that Biotech in the early clinical stage may also face more mergers and acquisitions, because VC will have to make some choices and continue to invest funds in proof-of-concept data .
On the other hand, uncertainties remain. M&A may remain scarce if big pharma prefers to partner with biotechs rather than acquire them. It depends on each MNC's cash reserves on hand and strategic shifts.
Sanofi has expressed its concern about outbound investment. In January, the company announced it would inject $750 million into its venture capital arm to pursue more business growth and acquisitions.
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