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With the release of successful clinical data, many biopharmaceutical and biotech company “stories” have performed perfectly in 2017. Many companies have achieved milestone results, such as the first genetically modified living cell. Drugs (CAR-T therapy) received FDA approval. Of course, there are some painful new drug projects. For example, a legendary company such as Axovant failed to survive the Alzheimer’s disease.

 

Late last year, Xconomy released the most anticipated 14 key clinical studies in 2017. At the dawn of the New Year, Xconomy counts on the most anticipated key clinical studies in 2018, covering such hot areas as cancer, liver disease, anemia, and spinal muscular atrophy. Here’s an introduction for everyone.

1. Checkmate-227 study

 

Company: Bristol-Myers Squibb (BMS)

Indications: Lung cancer

Announcement time: 2018 first half

Lung cancer is the second leading cause of death in the world. With the fierce competition of large drug companies in emerging cancer immunotherapy, the treatment of lung cancer changes each passing day. In October 2015, the FDA approved BMD’s Opdivo and Merck’s Keytruda for second-line treatment after chemotherapy. In 2016, Keytruda won a key phase III study of first-line monotherapy for NSCLC, and Opdivo suffered an unexpected failure. Keytruda became the first cancer immunotherapy drug approved for single-drug first-line treatment of patients with PD-L1 high expression of NSCLC.

 

The fierce competition in the lung cancer field has not ended. The clinical competition for PD-1/PD-L1 combined with chemotherapy or other drugs that can activate the immune system is in full swing. Keytruda continued to consolidate its advantages. In May of this year, it was approved to use combination chemotherapy for the first-line treatment of metastatic non-squamous NSCLC, regardless of PD-L1 expression levels. Just yesterday, Roche’s IMpower150 study showed that PD-L1 mAb Tecentriq combined with chemotherapy, bevacizumab first-line treatment of advanced NSCLC can reduce the risk of disease deterioration or death by 38%.

 

In 2018, BMS will publish the results of a critical Phase III Checkmate-227 study involving 2,220 patients. This combination of Opdivo+ Yervoy has been approved for the treatment of melanoma, and what kind of data can be made available for first-line treatment of NSCLC. At the same time, the interim results of the confirmatory Keynote-189 study of pembrolizumab combined with chemotherapy and the updated Mystic study of the combination of AstraZenem durvalumab+ tremelimumab should be published in the same period.

 

If the above three studies can achieve positive results, it will once again change the treatment of lung cancer.

2. KEYNOTE-252 Study

 

Company: Merck/Incyte

Indications: melanoma

Announcement time: 2018 first half

Merck has carried out hundreds of clinical research projects with KEYNOTE numbering. The reason why it concerns KEYNOTE-252 is as follows.

First of all, melanoma is the first indication of disease as an inhibitor of immune checkpoints as a monotherapy. However, the response rate is not as high as that of lung cancer. Therefore, it is very urgent to find an immunotherapeutic combination that can increase the response rate. However, the elimination of the immunosuppressed state of the immune system has multiple side effects, which may cause safety problems. Opdivo+Yervoy is currently the only approved I-O combination in the field of melanoma, but there is also the problem of poor tolerance. The KEYNOTE-252 study included 700 patients and examined the efficacy and safety of pembrolizumab in combination with Incyte’s IDO inhibitor epacadostat. IDO is an enzyme in vivo that helps tumor cells escape immune surveillance. Merck said that pembrolizumab+epacadostat can perform better.

Secondly, IDO is an extremely hot target at present, and it has attracted much attention in any event. Genentech and Newlink established a partnership based on the IDO inhibitor GDC-0919 (NLG919) in October 2014, but the two parties terminated their cooperation in 2017 and Roche returned GDC-0919’s development rights. BMS acquired Flexus Biosciences in preclinical stages with an astonishing $1.25 billion in 2015. BMS said that its IDO project has produced exciting results in the early studies of bladder cancer and cervical cancer.

 

KEYNOTE-252 will be the first confirmatory clinical study of large pharmaceutical companies investing in IDO tuyere, which may be good news for melanoma patients in urgent need of other treatment options.

3. 1002FDC-053 Study

Company: Esperion Therapeutics

Disease: Cardiovascular

Announced: Mid-2018

PCSK9 inhibitors can significantly reduce the body’s low-density cholesterol lipoprotein content. In 2015, the FDA approved the listing of Reroelement alirocumab (Praluent) and Amgen evolocumab (Repatha) for patients with hyperlipidemia who are intolerant to standard statins treatment or need additional drugs to improve blood lipid control.

 

However, Medicare payers don’t have a cold for these new lipid-lowering drugs that are priced at up to $14,000 per year. They are waiting for them to get clinical evidence that they can reduce heart attacks and strokes. In March this year, Amgen announced that evolocumab was shown to reduce the risk of heart attack in large clinical studies, but Repatha’s sales did not improve. The large-scale ODYSSEY OUTCOMES study of Regeneration will announce the results in the coming months, but Amgen’s experience shows that the payer wants to reduce the price of new drugs such as PCSK9. This is why we are extremely concerned about the 350-person Phase III study of the bempedoic acid of Esperion.

 

Bempedoic acid is a synthetic, dicarboxylic acid derivative administered orally, which has a dual regulatory effect on liver adenosine triphosphate citrate lyase (ACL) and adenosine monophosphate-activated protein kinase (AMPK) . The 1002FDC-053 study will examine the efficacy and safety of two-in-one tablets consisting of bempedoic acid and ezetimibe. Previous studies have suggested that the entire combination will be a more effective and less costly new lipid-lowering therapy than PCSK9 inhibitors. The most impressive data is that in the Phase II study, bempedoic acid combined with atorvastatin reduced LDL levels by 64% after 6 weeks of treatment.

 

The 1002FDC-053 study will compare the efficacy and safety of bempedoic acid plus ezetimibe, bempedoic acid, ezetimibe, and placebo, and will provide clearer evidence for the clinical outlook of bempedoic acid.

4. BELIEVE, MEDALIST Study

 

Company: Acceleron

Disease: Beta-thalassemia/myelodysplastic syndrome

Announced: Mid-2018

Patients with inherited blood disorders such as beta-thalassemia require blood perfusion once a month to prevent the occurrence of fatal anemia. In addition, they usually need iron ion chelation therapy to relieve the iron ion overload that may be caused by blood perfusion. Acceleron’s luspatercept is expected to provide a new treatment option for patients with beta-thalassemia.

 

Luspatercept is a modified ActIIB receptor fusion protein administered subcutaneously. By binding the ligand to the TGF-β superfamily to stimulate late red blood cell maturation, hemoglobin concentration can be increased and blood transfusions can be reduced. In phase II studies, Luspatercept brought clinical benefits to beta-thalassemia or other diseases that can cause anemia and morning medications (such as myelodysplastic syndromes). Patients have more oxygen-carrying hemoglobin and need blood transfusions. The number of drops.

 

Acceleron and its partner Celgene currently conduct three phase III studies. Believe (β-thalassemia) and MEDALIST (myelodysplastic syndrome) are expected to publish results in mid 2018. If positive results are obtained, they will develop treatments for the same patients. Bluebird Bio, a beta-thalassemia gene therapy, has caused a lot of pressure.

5. STR1VE study

 

Company: Avexis

Disease: Spinal muscular atrophy

Published: TBA, 2018

Biogen and Ionis created history in December 2016. Their jointly developed nusinersen (Spinraza) was approved by the FDA for marketing and became the first drug to treat spinal muscular atrophy. Spinal muscular atrophy is a rare and fatal genetic disease that mainly affects muscle strength and exercise. The main manifestations of the patient are general muscle atrophy, loss of various motor functions, and even breathing and swallowing. The age of onset, symptoms, and rate of progression are highly variable.

 

Nusinersen is an antisense oligonucleotide that alters the splicing of the SMN2 gene, increases the production of full-function SMN proteins, and can delay progression of multiple types of spinal muscular atrophy. The question now is: How much benefit can this breakthrough new drug bring to patients? How many patients can eventually help? In the first year of Spinraza’s $750,000 and then the $375,000 a year pricing system, this problem has been significantly amplified.

 

Last month, AveXis launched a Phase III study, code-named STR1VE, to examine the efficacy and safety of AVXS-101 in the treatment of the most severe form of spinal muscular atrophy in infants. AVXS-101 is a gene therapy in which all 15 SMA infants who received a single dose of AVXS-101 injection survived the 20th month in a small phase I study and achieved event-free survival. No breathing machine was needed to assist breathing during the time, and no major safety issues were found.

The researchers said that similar SMA patients have only 8% survival rate without treatment, and can AVXS-101 succeed in a larger phase II study? If yes, can AVXS-101 compete directly with nusinersen? Or as a combination therapy to enhance efficacy? The combined price of the two is undoubtedly astronomical, but whether the economic and social benefits of AVXS-101 can be matched with the price can only be answered after seeing the clinical data of STR1VE.

6. STEADFAST Study

Company: vTv Therapeutics

Disease: Alzheimer’s disease

Announcement time: first half of 2018

The United States currently has 5 million people with Alzheimer’s disease, and this number will reach 16 million in the middle of this century. Alzheimer’s disease can cause huge losses both in the family of patients and in society as a whole. Every failure to treat Alzheimer’s disease has highlighted the urgency of the task.

Recently, a large IPO of Axovant’s intepirdine in the treatment of mild to moderate phase III clinical studies of Alzheimer’s disease (AD) has failed to reach the primary efficacy endpoint, failing to improve patient perception.

The first important figure in 2018 should be the azeliragon that Pfizer suffered in 2011. After TransTech Pharma bought the failed project, it launched another 800-person phase III study in 2015 (TransTech later merged a North Carolina biologic company and changed its name to vTv). Jeff Kindler, who was the CEO of Pfizer before 2010, is now the CEO of vTv.

Regardless of good or bad, the data is worthy of attention. Azeliragon is currently recognized as the most advanced drug that blocks the brain receptor RAGE (advanced glycation end product receptor). vTv believes that blocking RAGE can attack three ways: disrupting the accumulation toxicity of Alzheimer’s disease amyloid fragment; slowing down the decomposition of tau protein associated with it; and reducing brain inflammation. Recently, some researchers have called for people with Alzheimer’s disease to consider multiple targets at once, rather than just using a “one size fits all” approach to fight amyloid.

Azeliragon also has some concerns. Patients recruited with vTv were either amyloid-free or PET-proteinized with amyloid and did not consider magnetic resonance imaging.

vTv also reviewed previous low-dose patient data. Reinterpreting data for planning new, expensive research is a controversial way. In Alzheimer’s disease, vTv is not the first attempt, they may be the first successful enterprise.

7. NCT02781584, NCT02854605

Company: Gilead

Disease: Nonalcoholic steatohepatitis (NASH)

Announcement time: first half of 2018

Non-alcoholic steatohepatitis (NASH) is an increasingly common liver disease. The FDA has not approved any therapeutic drugs and is one of the most competitive battlefields in drug development. Healthy people cause fat to accumulate in the liver by eating too much sugar and fat. If the disease is not controlled, inflammation and scars will follow and even require liver transplantation. NASH affects about 2% to 3% of the Western population.

There is currently a large wave of companies, including Intercept, Gilead, Allergan, BMS, and GenFit all have layouts in this area. Intercept’s FXR receptor agonist is obeticholic acid is the longest, phase III data is expected to be announced in 2019. Gilead had two sets of interesting data in 2018.

In fact, Gilead has 3 drugs in this field. The first one is GS-9674, which was purchased from German bio-company Phenex in 2015. Like obeticholic acid, it is also an FXR receptor agonist; the other is GS-0976. , bought from Nimbus in 2016. Earlier this year, Gilead released the second phase of GS-0976 data, which can block an enzyme called acetyl CoA carboxylase, which reduces liver fat accumulation and biomarkers that reduce liver scars. The level of material; in addition Selsontrib is conducting a phase III trial of STELLAR, and it is expected that no data will be published in the next few years.

8. ANDES, HIMALAYAS, SIERRAS RESEARCH

Company: FibroGen

Disease: Anemia

Published: TBA, 2018

Epoetinalfa (Epogen) was discovered in the 1980s and was originally a naturally occurring substance in the body – a hormone secreted by the kidneys that stimulates the regeneration of red blood cells. As a tremendous advancement in healthcare, it is now a biological medicine that can treat anemia in patients with renal failure.

In the past few years, Epogen and similar drugs have brought billions of dollars in income for Amgen. However, due to the increasing number of serious heart problems, the FDA has tightened the control of this drug, once new drugs are available. It is likely to be replaced. If large-scale studies can prove that new drugs and Epogen are equally effective and safer, the rewards can be enormous. According to the report of Allied Market Research, the global market for these drugs will reach 11.9 billion U.S. dollars by 2020.

 

Epogen’s first competitor is FibroGen’s vadadustat and another competitor is Akebia’s vadadustat, which claims to stimulate more red blood cell production at high altitude and in a low oxygen environment. Both FibroGen and Akebia are conducting large-scale, expensive phase III trials to compare with the Epogen head-to-head.

FibroGen will publish phase III data from the Andes, Himalayas, and Sierras study in 2018, and Akebia’s three phase III clinical trials will be completed by the end of 2019.

9. PROMISE 2 Study

Company: Alder Biopharmaceuticals

Disease: Migraine

Announcement time: first half of 2018

Calcitonin gene-related peptide (CGRP) inhibitors, which inhibit pain transmission, are the main migraine drug types at present. Although Alder was the first to initiate clinical trials, erenumab, galcanezumab, and Teva (TEV-48125) have submitted FDA listings. Alder is a small company and there is currently no product approved by the FDA.

 

Alder developed this migraine drug, peptinezumab, which is an intravenously injected monoclonal antibody. Unlike the products of Amgen and Lilly that need to be injected once a month, eptinezumab is expected to achieve quarterly injections. Teva previously reported that his family also injected once every 3 months. According to Randy Schatzman, CEO of Alder, the selling point of eptinezumab is subcutaneous injection. However, in order to provide patients with multiple options, they will be the first to submit an injection application.

 

EPTinezumab’s PROMISE 1 study included patients with paroxysmal migraine who had 5 to 14 episodes per month, and the PROMISE 2 and PROMISE 3 studies recruited more than 1,000 chronic migraine patients who had more than 15 episodes per month. Alder plans to submit an application to the FDA for the treatment of paroxysmal and chronic migraine in the second half of 2018.

10. PALISADE Study

Company: Aimmune Therapeutics

Disease area: peanut allergy

Announcement time: first half of 2018

In Europe and the United States, it is estimated that 30 million people are allergic to a certain type of food, of which peanut allergy is the most common type of allergy. Aimmune’s drug candidate AR10 allows peanut allergies to eat peanuts normally.

In a randomized phase II study, 6 out of 55 patients withdrew because of intestinal side effects. Aimmune said these problems were resolved after the patient stopped taking the drug. In 2016, Aimmune’s Phase III PALISADE study completed the recruitment of 554 patients.

 

Although the FDA did not approve allergy drugs similar to those developed by Aimmune, DBV Technologies in Paris has developed a skin patch called Viaskin for treating peanut allergy. DBV announced early data on more than 700 patients last month.

 

It is worth mentioning that Aimmune’s research attracted the attention of the big players in the food industry. Nestlé Health Sciences conducted exclusive negotiations with him for three months and purchased Aimmune stock valued at US$145 million. Aimmune expects to submit a listing application to FDA and EMA by the end of 2018.

11. Moderna’s Phase I Study

Company: Moderna Therapeutics

Disease: Flu

Published: TBA, 2018

Moderna Therapeutics is a highly forbidden and mysterious privately held company. The company was valued at $5 billion a few months ago.

Moderna injects synthetic messenger RNA (mRNA) into the patient, which is used to develop the artificial proteins needed by the patient. In other words, Moderna wants to turn the patient’s own body into a pharmaceutical factory. This idea is unique, but Moderna currently provides too little data, causing some people to question its high valuation. Moderna said that in 2018, clinical data and more substantive results will be published for the first time.

 

This year, Moderna announced that the flu vaccine for mRNA development has shown good tolerability in both clinical trials. Moderna plans to publish Phase I studies of mRNA-1440 and mRNA-1851 targeting H10N8 and H7N9 influenza strains next year. The H10N8 and H7N9 influenza strains have the potential to cause flu pandemic. H7N9 bird flu can be transmitted to humans. It has infected more than 1,500 people worldwide, and about 40% of them have died. H10N8 is another bird flu virus and only a few people are infected. Currently, there are no vaccines approved for H10N8 and H7N9.

 

In addition, Moderna’s early projects in the field of cancer and infectious diseases will also be announced in 2018, but the flu product line is Moderna’s most imaginative product of mRNA technology. Otherwise, what does Moderna compare to its high valuation?

12. ENLIGHTEN-2 Study

Company: Alkermes

Disease: Schizophrenia

Published: 3Q2018

A common side effect of psychiatric drugs is weight gain. ALKS3831, a candidate drug developed by Alkermes, promises to avoid the side effects of weight gain, but in an international multicenter, double-blind, randomized, controlled (control) olanzapine study codenamed ENLIGHTEN-1, ALKS 3831 is better than placebo. Schizophrenia has a better effect, but the test group’s weight has increased. Alkermes executives said that the trial period was only 4 weeks and did not explain the fact that ALKS3831’s body weight will increase after treatment. Alkermes hopes to conduct another independent phase III study in the ENLIGHTEN-2 project.

 

Although Zyprexa is a proven and effective atypical antipsychotic, it has been out of favor due to the risk of type 2 diabetes. ALKS 3831 combined with Olanzapine generic drugs and another compound samidorphan combined to reduce weight. Alkermes plans to complete 540 patient recruitments next year; first-line data is expected to be announced in the fall of 2018.

13. Sangamo’s Phase I Study

 

Company: Sangamo Therapeutics

Disease: Hunt’s Syndrome

Published: 2018

 

As of now, the FDA has approved two CAR-T therapies. In addition, some companies have demonstrated the potential of gene therapy in the treatment of rare eye diseases and beta-thalassemia. The next major medical breakthrough will be genetic editing.

In theory, genetic editing can change DNA more precisely in the body. Although everyone is currently focused on the CRISPR-Cas9 system, Sangamo Therapeutics uses the ZFNs (Zinc Finger Nuclease) system.

 

This treatment involves the use of genetic editing techniques to cut off DNA helices in liver cells and insert a replacement copy of the gene. This will transform the genetically modified stem cells into a manufacturing facility that will continue to manufacture the missing enzymes for Hunter Syndrome patients. Its best condition is to use the existing enzyme instead of the drug for lifelong treatment. But no one knows how long the long-term changes in individual genes will last, and whether they will continue to work.

 

Sangamo’s spokesperson stated that as more and more patients are added, some data will be released in 2018 (the company also plans to conduct similar research in patients with hemophilia B and type I mucopolysaccharidosis). At present, no CRISPR-based therapy has been tested in humans. CRISPR clinical trials may occur in 2018, but those companies did not announce specific times.

 

In addition, CRISPR-Cas9 and its variants have been used in academic and industrial laboratories around the world, and key patents for ZFNs have been held by Sangamo. There may be some patent disputes next year.

14. TRANSCEND study

Company: Juno Therapeutics

Disease: Non-Hodgkin’s lymphoma

Announced: Second half of 2018

 

The first academic project, the first clinical patient, the first important biologic license, the first IPO, the first clinical setback, the FDA’s first approval, the first large-scale acquisition … CAR-T is almost every A few months will bring a “first”.

In 2018, two major rivals in the CAR-T field, Gilead and Novartis, will be confronted in the treatment of adult non-Hodgkin’s lymphoma. Although JUNO has already won the first place in many fields, it has not really stood out from the crowd. If the TRANSCEND test project goes well, it will have more than one CAR-T product, and in 2019 it may even go green. Although Kite’s Kite and Novartis’ CAR-T therapy will be commercially available, JUNO’s story must be a huge leap forward: better efficacy, better safety.

 

In the past year, JUNO has been trying to emerge from the shadow of its star candidate product JCAR015 leading to patient death. JUNO said that of the 15 patients treated with the high-dose CAR-T product JCAR017, 11 patients had no tumor after 3 months, but in order to stand out, JUNO’s products must produce better results. Despite being in phase 1, JUNO’s TRANSCEND study will recruit enough patients to have sufficient data to support their application to the FDA in the second half of 2018.

15. Phase I study

Company: City of Hope

Disease: Brain cancer

Announcement time: end of 2018

 

One of the must-recommendations is the City of Hope, a cancer center in Duarte, 20 miles east of downtown Los Angeles. It is the 40 cancer integration centers designated by the National Cancer Institute. one.

 

Although CAR-T has already proved its strength in the field of hematology and oncology, the biggest problem is whether it can treat solid tumors. After all, this is the case of most cancers. Glioblastoma is a late and difficult-to-cure brain tumor. City of Hope announced in December 2016 that its improved CAR-T cells were used to treat a case of glioblastoma, extending the patient’s life expectancy by seven and a half months.

 

According to published trial records, this brain cancer study may produce data by the end of 2018. The good results will not only make CAR-T a huge step forward, but also bring confidence to California’s stem cell companies. The latter received US$13 million in funding support and investors are eager to see results.

 

Christine Brown, a T-cell researcher at City of Hope, said that there are currently 55 to 70 patients of varying degrees who will eventually receive treatment. No matter how good the data is, it must eventually be able to replicate industrially. Manny Litchman, CEO of Mustang Bio (NASDAQ: MBIO), a New York-based CAR-T cell company, was proficient in CAR-T. He was responsible for signing cooperation with the University of Pennsylvania at Novartis, and it was the key role that resulted in the first case of CAR-T being approved by the FDA. He believes that City of Hope’s plan to publish data in December 2018 is somewhat radical.

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