Top 10 Biopharma Stories of 2019

This year marked yet another series of interesting, exciting and occasionally puzzling stories coming out of the biopharma industry. Our breaking news writers, Alex Keown and Mark Terry, picked their top 10 stories of the year.

Biogen’s Aducanumab Rollercoaster Ride

For the last few years, as Alzheimer’s drug after Alzheimer’s drug met with failure, Biogen’s aducanumab appeared to be the last best hope, even though many critics were skeptical. Then, in March 2019, Biogen and its collaboration partner, Tokyo-based Eisai, announced they were discontinuing the global Phase III trials, ENGAGE and EMERGE, of aducanumab in patients with mild cognitive impairment from Alzheimer’s, as well as the EVOLVE Phase II trial and the long-term extension PRIME Phase Ib trial. An independent data monitoring committee indicated the trials were unlikely to hit their primary endpoints in a futility analysis.

But in late October, the companies announced that after discussions with the U.S. Food and Drug Administration (FDA), and further analysis of the data, they were going to pursue regulatory approval for the drug. The Phase III EMERGE trial met its primary endpoint, showing a significant decrease in clinical decline. The company believes that data from a subset of patients that were given a high enough dose of the drug had significant benefits on measures of cognition and function, including memory, orientation, and language, as well as benefits on activities of daily living.

On Dec. 5, the company presented full data on aducanumab at the 12^th Clinical Trials on Alzheimer’s Disease (CTAD) conference to held in San Diego. And the results were … more of a rollercoaster ride. Although there were positive data that’s very intriguing, there were some concerning safety signals and a mixed result between the two trials that are likely to have the FDA debating intensely over whether the drug should actually be approved. In that respect, the rollercoaster ride is unlikely to be over.

Ebola Vaccine Approved in Europe

The European Commission approved the world’s first Ebola vaccine. The vaccine is manufactured by Merck & Co. and has a trade name of Ervebo.

“The European Commission’s marketing authorization of Ervebo is the result of an unprecedented collaboration for which the entire world should be proud,” said Kenneth C. Frazier, Merck’s chairman and chief executive officer. “It is a historic milestone and a testament to the power of science, innovation and public-private partnership.”

Ervebo was being used under a “compassionate use” program in the eastern Democratic Republic of Congo (DRC), where there has been the second-largest Ebola outbreak on record. Since August 2018, more than 3,000 people in the country have tested positive for Ebola and more than 2,000 people have died of it. In the last year, more than 250,000 people have been dosed with the Merck vaccine in DRC.

Another Ebola vaccine being developed by Johnson & Johnson, is being administered to 50,000 people in Goma, a city with two million people on the Rwandan border of eastern Congo. The J&J vaccine requires two injections eight weeks apart, while the Merck vaccine only requires a single shot.

Moratoriums on Heritable Genome Editing

In the wake of the 2018 scandal caused by a Chinese researcher’s use of CRISPR-Cas9 gene editing to alter the DNA of embryos for seven couples, leading scientists called for a moratorium on heritable genome editing.

In November 2018, He Jiankui, a researcher in Shenzhen, China, announced that he had used CRISPR to disable a gene called CCR5 in the embryos of seven couples. All the men in the seven couples had controlled HIV, but the women did not. The gene editing’s goal wasn’t to prevent transmission of HIV, but, He claimed, to give the children protection. A set of twins were born and at least one other woman is pregnant.

The call for a moratorium was written by 18 leading researchers and bioethicists from seven countries, including Feng Zhang and Emmanuelle Charpentier, who in separate labs, are noted as the competing inventors of CRISPR.

The moratorium does not call for a permanent ban, but states, “Rather, we call for the establishment of an international framework in which nations, while retaining the right to make their own decisions, voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met.”

Tel Aviv University Researchers 3D-Print a Human Heart

There has been significant progress in so-called bioprinting—using a type of 3D printing to manufacture biological tissues. But an actual organ hadn’t been accomplished—until now.

Researchers at Tel Aviv University successfully printed the first 3D human heart. The research team used the patient’s own cells and various biological materials such as collagen and glycoprotein.

“This heart is made from human cells and patient-specific biological materials,” stated Tal Dvir, lead researcher. “In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models. People have managed to 3D-print the structure of a heart in the past, but not with cells or with blood vessels. Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future.”

This is only one big story this year showing how far we’ve come and the direction we’re headed in 3D-printing organs for research purposes and potentially for organ replacement.

Roivant’s $3 Billion Deal with Sumitomo Dainippon Pharma

Although not as big a deal as, say, Bristol-Myers Squibb’s $74 billion acquisition of Celgene, the sale of five ‘Vant companies under Vivek Ramaswamy’s umbrella company, Roivant Sciences, marked a validation of Ramaswamy’s business model and approach to biotech companies. The deal was originally announced in September, but more details came out in November.

Roivant sold ownership of five ‘Vant companies to Japan’s Sumitomo Dainippon Pharma for $3 billion. Sumitomo Dainippon also was buying an equity stake of more than 10% of Roivant shares.

Sumitomo will create an as-yet unnamed company to shift the five companies into. They will be run by Myrtle Potter, a former Genentech executive who has been the operating chair of Roivant since July 2018.

There is a $3 billion upfront fee. In addition, Sumitomo will offer a $350 million loan facility to Myovant to fund the launch of relugolix, its Phase III candidate for uterine fibroids if it is approved. The Japanese firm will also loan Urovant $200 million for its vibegron for overactive bladder.

If Sumitomo options the other six companies, it will have acquired a pipeline of more than 25 clinical programs with multiple possible launches from 2020 to 2022. In addition to buying the five initial companies, the deal gives Sumitomo access to Roivant’s proprietary technology platforms, DrugOme and Digital Innovation. It will also enter separate strategic client relationships with Datavant and Alyvant.

The five Vant companies are Myovant Sciences, Urovant Sciences, Enzyvant Therapeutics, Altavant Sciences, and Spirovant Sciences. Spirovant is a new Vant that focuses on developing gene therapies for cystic fibrosis.

The Fall of Purdue

The year 2019 marked the fall of Purdue Pharma, the makers of OxyContin. In September, Purdue filed for bankruptcy and agreed to pay $10 to $12 billion in legal settlements after thousands of lawsuits were filed against the company over its aggressive marketing tactics for OxyContin. State and local government entities accused the company’s maneuvers of contributing to the opioid crisis in the United States, a crisis that has resulted in thousands of opioid-related overdose deaths.

While the company is filing for bankruptcy, it will continue under a new management structure. The new company will be governed by a board selected by the claimants and approved by the bankruptcy court. When the new company is formed, it will contribute “tens of millions of doses” of opioid overdose reversal medications and treatments aimed at opioid addiction at little or no cost, such as nalmefene and naloxone.

In addition to 100% of Purdue’ assets being included in the bankruptcy, the Sackler family, which is the majority owner of the privately-held company, agreed to contribute a minimum of $3 billion, with the potential for substantial further monetary contributions from the sales of their ex-U.S. pharmaceutical businesses, such as Mundipharma, which has been pegged at a value of about $1.5 billion throughout the settlement discussions.

Year of the Carcinogen-Related Recalls

While drug recalls are not uncommon due to a myriad of issues, 2019 seemed to have a number of them all involving issues with carcinogens discovered in the manufacturing process. The year began with a number of recalls of blood pressure medications that were found to have carcinogens present. The FDA recalled lots of different types of angiotensin II receptor blockers from different manufacturers due to the presence of an impurity called N-Nitroso-N-methyl-4-aminobutyric acid (NDMA), a known carcinogen. Companies like Teva and Camber Pharmaceuticals recalled lots of Amlodipine and losartan potassium tablets that were found to be contaminated with NMBA, a known environmental contaminant. With the multiple lots recalled over the course of months, it was inevitable that lawsuits would be filed regarding the tainted blood pressure medications.

It wasn’t just blood pressure medications that were found to have been contaminated. Ranitidine tablets, which are used to decrease the amount of acid created by the stomach, have also been recalled due to the presence of NDMA. In November, Aurobindo joined the likes of Sanofi, GlaxoSmithKline, Novartis, Dr. Reddy’s Laboratories, Perrigo, Novitium Pharma and Lannett Company in the recall of ranitidine tablets.

Keytruda Becomes a Cornerstone of Cancer Treatment

During an Investor’s Day conference in June, Merck‘s Chief Commercial Officer Frank Clyburn said in a short time, Keytruda has become a foundational cancer treatment. “We have activity across 25 different cancer types… and Keytruda is changing the way in which patients are being treated today,” Clyburn said at the time. And with the number of approvals Merck’s vaunted checkpoint inhibitor keeps racking up, Clyburn’s words are proving not to be a boast to boost share prices. In fact, analysts have pegged Keytruda to become the number one selling drug in the world by 2025, supplanting AbbVie’s Humira, which loses patent protection in 2023. Keytruda has been approved more than 22 times since 2015 and is well on its way to earning more.

Most recently, Merck announced that Keytruda, used as a monotherapy, demonstrated significant improvement in overall survival, progression-free survival and overall response rate in patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) whose tumors expressed PD-L1 regardless of KRAS mutation. In its analysis of the data, Keytruda reduced the risk of death by 58% in patients with any KRAS mutation and by 72% in patients with the KRAS G12C mutation compared to chemotherapy. With a new year on the horizon, it’s likely more approvals for Keytruda are as well.

Continued Improvements in HIV

In November, researchers at Abbott Laboratories discovered a new strain of HIV, the first such subtype of HIV-1 in nearly two decades. The researchers uncovered a new subtype of “Group M” HIV virus, whose origins can be traced to the Democratic Republic of the Congo in Africa. The discovery of the new strain means researchers can begin to develop potential new therapies aimed at it. Since the start of the global AIDS epidemic, more than 75 million people have been infected with HIV. At one time, it was a virtual death sentence, however, with the development of new medications and treatments, more than 37.9 million people are able to control their virus and continue living productive lives.

There have been a number of new approvals for HIV this year, including Merck’s Pifeltro and Gilead Science’s Descovy for HIV pre-exposure prophylaxis. There are also numerous potential treatments in the pipelines of companies, including bone marrow transplants using CRISPR technology and regulating the protein BRD4, which has been seen as a potential cure for the disease. There has also been potential for a cure in the genetic modification of long noncoding RNA. With the promising work done in 2019, 2020 could bring even more treatment options for HIV patients.

Year of the Mega Mergers

Mergers and acquisitions are part of the ever-changing landscape of the pharma and biotech industry. But this year, there have been several large-scale changes to the landscape as some of the biggest companies have become one. It all started in January when Bristol-Myers Squibb announced it was acquiring Celgene for $74 billion. The merger of the two pharma giants created a powerhouse in oncology, hematology, immunology and cardiovascular disease. Since the merger, the combined companies have seen several new regulatory wins, including the FDA approval of Celgene’s Reblozyl (luspatercept-aamt) for the treatment of anemia in certain adult patients with beta thalassemia.

Six months later, in June, AbbVie announced a “transformational move” with the $63 billion acquisition of Botox-maker Allergan. When the deal was announced, AbbVie said the addition of Allergan’s pipeline and products would deliver immediate scale to the company’s growth platform, as well as meet its strategic goal to reduce reliance on Humira, which has been the primary cash cow of the company. The combined companies will have several strong franchises across immunology, hematologic oncology, medical aesthetics, neuroscience, women’s health, eye care and virology.

While those were the two biggest mergers of 2019, there have been others that will certainly change the landscape, including Mylan’s merger with Pfizer’s off-patent medicines company, Upjohn. The new company is already projected to post 2020 revenues of $20 billion. The new company will have numerous well-known brands in its portfolio, including the Epi-Pen, Viagra, Lipitor, Celebrex and others.