Toward the end of every year, biopharma executives are asked to dust off their crystal balls and predict what the next year might reveal. It’s that time of year again! Find out what execs are saying about M&A, gene therapy, sickle cell, and more.
Toward the end of every year, biopharma executives are asked to dust off their crystal balls and predict what the next year might reveal. It’s that time of year again!
For example, as 2017 was ending, and the government was wrapping up a tax overhaul that cut corporate taxes, many thought 2018 would be a huge year for mergers and acquisitions (M&A). A BioPharmaDive poll picked the most obvious acquisition targets as Spark Therapeutics, Tesaro, Axovant Sciences and Biogen.
Oops. Although it wasn’t a bad year for M&A, none of those companies were acquired this year. The biggest deal, still pending, is Shire’s acquisition by Takeda Pharmaceutical for about $62.2 billion. The year began with some large and largely unexpected deals by Paris-based Sanofi, which acquired Waltham, Mass.-based Bioverativ for about $11.6 billion and then Ghent, Belgium-based Ablynx for $4.8 billion about a week later. And January also marked Celgene’s acquisition of Juno Therapeutics for about $9 billion.
Polled executives also had a lot of interest in changes with pharmacy benefit managers (PBMs) like Express Scripts, which cut out 64 branded drugs from its 2018 formulary and CVS Health removing 17 branded drugs from its formulary.
No one was quite ready for CIGNA Corporation to buy Express Scripts in March for $67 billion. A number of biopharma executives, including Leonard Schleifer, co-founder of Regeneron Pharmaceuticals and Pfizer’s chief executive officer Ian Read, strongly criticized PBMs for their role in high drug prices, particularly in the area of so-called rebates that PBMs are supposed to pass on to patients, but often acts more like kickbacks to encourage PBMs to include certain drugs on their formularies.
While keeping in mind that predictions are, er, educated guesses, let’s look at what some executives are thinking about 2019.
Gene Therapy
Pavan Cheruvu, chief executive officer of Axovant Sciences, thinks next year will be a hot one for gene therapies. He told Life Science Leader, “I believe 2019 will be a golden year for gene therapies targeting neurological and neuromuscular conditions. Our understanding of the underlying biology of neurologic diseases, including genetically-driven conditions, is profoundly greater today than it was even two years ago, and this has given rise to a third wave of therapies focused on genetic insertion, silencing, or modification.”
Cheruvu no doubt is hopeful. In June, the company licensed exclusive worldwide rights to OXB-102, now called AXO-Lenti-PD from Oxford BioMedica. It’s an investigational gene therapy for Parkinson’s disease. The company dosed its first patient in a Phase I/II dose-escalation trial in patients with advanced Parkinson’s disease in October and expects initial data from the first cohort in the first half of 2019.
Sickle Cell Disease
Ted Love, president and chief executive officer of Global Blood Therapeutics (GBT) expects both large and small companies to come up with treatments for sickle cell disease. “The recent influx in SCD research,” he told Life Science Leader, “is due in part to the FDA’s support of initiatives to better understand how the complex manifestations of this disease can be most appropriately assessed in clinical trials.”
Perhaps not surprisingly, GBT in June reported positive data from Part A of its Phase III HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study of voxelotor for sickle cell disease. The drug works by increasing hemoglobin’s affinity for oxygen. It has received Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations from the FDA.
Also, on November 27, Roivant Sciences teamed with Cincinnati Children’s Hospital Medical Center to launch Aruvant Sciences, to focus on gene therapies for sickle cell disease and beta-thalassemia. They also formed a new nonprofit foundation, the Roivant Foundation, to work to improve access to medical care for patients with sickle cell disease in the developing world.
The Tumor Microenvironment and Next-Generation Immuno-Oncology
Adelene Perkins, chief executive officer and chair of Infinity Pharmaceuticals, thinks that a new aspect of immuno-oncology is going to come to the forefront of the industry, which is the impact of the tumor microenvironment.
“Because,” Perkins told Life Science Leader, “while checkpoint inhibitors provide a significant benefit for some patients, the vast majority do not respond to this therapy, and some who do may ultimately relapse. This new problem, and the groundbreaking research directed to a solution, has revealed that even in the presence of checkpoint inhibitors the tumor microenvironment can counteract and suppress an immune response. In other words, activating the immune system with checkpoint inhibitor therapy alone for some patients isn’t enough.”
On November 10, Infinity presented positive data at the 33rdAnnual Meeting of the Society for Immunotherapy of Cancer (SITC) from a Phase Ib clinical trial of its IPI-549 plus Bristol-Myers Squibb’s Opdivo in chemotherapy-resistant triple negative breast cancer (TNBC) and in advanced solid tumors such as microsatellite stable (MSS) gallbladder cancer and adrenocortical carcinoma. IPI-549 is an investigational first-in-class, oral, immuno-oncology drug candidate that targets tumor-associated myeloid cells via selective phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition. This effectively reduces pro-tumor macrophage activity and increases anti-tumor macrophage function.
On November 6, Pfizer partnered with Nektar Therapeutics to evaluate combination regimens in a variety of cancer settings. Those include metastatic castration-resistant prostate cancer (mCRPC) and squamous cell carcinoma of the head and neck (SCCHN).
As part of the collaboration, they will evaluate Nektar’s lead immuno-oncology candidate, NKTR-214 with avelumab. Avelumab is a human anti-PD-L1 antibody developed jointly by Germany’s Merck KGaA and Pfizer. They will also evaluate NKTR-214 with Pfizer’s talazoparib, a poly (ADP-ribose) polymerase (PARP) inhibitor and with enzalutamide, an androgen receptor inhibitor developed by Pfizer and Astellas Pharma.
NKTR-214 is a CD122-biased agonist. It is designed to expand specific cancer-fighting CD8+ effector T-cells and natural killer (NK) cells in the tumor microenvironment. It also increases expression of PD-1 on the immune cells.
CRISPR
BioSpace makes one more major prediction. On November 26, a Chinese researcher, He Jiankui, affiliated with the Southern University of Science and Technology of China in Shenzhen, used CRISPR-Cas9 gene editing to alter the DNA of embryos for seven couples in China. He was assisted by Michael Deem, one of his graduate advisers at Rice University in Houston. Deems also holds a small stake in two commercial genetics companies He Jiankui launched in China.
What He Jiankui and Deem did was use CRISPR gene editing on human embryos to disable a gene called CCR5. This gene creates a protein that allows HIV to enter a cell. All the men of the seven couples had HIV and the women did not. The goal wasn’t to prevent transmission of HIV, said He, because all seven men’s HIV infections were strongly suppressed by standard HIV drugs.
The CRISPR editing was performed during in vitro fertilization (IVF). The sperm was “washed” to separate it from semen, where HIV is present. Then a single sperm was inserted into a single egg to create an embryo. Then the CRISPR-Cas9 gene editing tool was applied.
When the embryos were 3 to 5 days old, several cells were examined for editing. At that time the couple could choose whether to go ahead and use edited or unedited embryos for their attempted pregnancies. In total, 16 of 22 embryos were edited and 11 were used in six implant attempts.
He Jiankui announced the research and the apparently successful birth of twins, Lulu and Nana, from one set of parents. The announcement came at an international conference on gene editing being held in Hong Kong. The research has not been published in a peer-review technical journal, although some researchers reviewed the work.
However, it didn’t take long for the announcement to create an uproar among scientists and ethicists worldwide. Southern University plans to investigate He Jiankui and Rice University is planning to investigate Michael Deems.
More than 100 Chinese scientists signed a letter condemning the research. In part, the letter said, “The bioethics approval for this so-called ‘study’ was insufficient. We can only use the word ‘crazy’ to describe the experiment conducted directly on human beings. We have much to debate inside the scientific community about the accuracy and off-target-effects brought by CRISPR. Any attempts to alter human embryos and make babies carry huge risks without strict examination beforehand.”
This story isn’t going to go away. CRISPR has too much potential to have a positive impact on healthcare and biopharma. There are a number of ongoing clinical trials utilizing the technology in the U.S., China and Europe, some of which will undoubtedly have readouts in 2019.
It’s possible that He Jiankui and Michael Deems will, in the future, be noted for their pioneering work in gene therapy and gene editing. But for now, most researchers believe the work was unnecessary, unethical and premature—as well as potentially very dangerous for the babies.
Still, expect CRISPR to play a central role in biopharma news in 2019.
