Review of 41 New Drugs Approved by FDA in 2017


Release time:

2017-12-10

Up to now, CDER has approved 41 new molecular entities, and the PDUFA deadline for 2 drugs falls in December. If FDA does not speed up the approval of new drugs in December, the number of new molecular entities approved in 2017 may be 41-43. Of course, the new drugs covered in this article are NDA or BLA accepted by CDER, and do not include CBER-reviewed varieties, such as CAR-T products. Compared with last year's 20 or so, this year is a bumper year. Of the 41 products that have been approved, 31 are approved for the first time in the world, 19 products have received priority review (P),13 have received breakthrough therapy certification (B),17 have received orphan drug qualification (O), and only 11 products except biological products are subject to standard review (O). According to the forecast of Corrivian analysts, more than 10 of these products will reach the blockbuster level (sales exceeding $1 billion) in the fifth year after approval.

However, every year there are several joys and several sorrows. First, Lilly's JAK inhibitor baritinib was refused approval by FDA, then Johnson & Johnson's IL-6R monoclonal antibody encountered Waterloo, Duchenne muscular dystrophy new drug Ataluren did not become the lucky darling like Exondys 51, and glaucoma new drug Netarsudil was voted by FDA expert committee to carry out new clinical trials......

Corey Vivian's Most Concerned Drugs in 2017

▋ NO. 01 Trulance(plecanatide)

On January 19, FDA approved Trulance(plecanatide),plecanatide is a GC-C (guanylate cyclase-C) agonist with linaclotide, and the approved indication is CIC (chronic idiotypic constipation). For CIC, the efficacy is comparable to linaclotide, but for IBS-C (constipation due to irritable bowel syndrome), the efficacy is not as good as linaclotide. The adverse reaction rate of this product is lower than that of linaclotide, and the rate of withdrawal due to severe diarrhea in clinical trials is much lower than that of linaclotide. In terms of structure, this product and linaclotide are both small molecule single peptides, but with one less disulfide bond, the synthesis difficulty will be much smaller, but the dosage is larger than linaclotide. The main indication of this kind of products is IBS-C. The daily dose of linaclotide is only 0.29mg, while that of pukanatide is 6mg, which is not obvious enough. This product sold for US $2.4 million in the first half of 2017. The sales volume in 2017 is under great pressure to break through 10 million. IBS-C indications are already under review and are expected to be approved in 2018.

Comparison of three anti-IBS-C drugs (Source: FDA)

▋ NO. 02 Parsabiv(Etelcalcetide)

Parsabiv(Etelcalcetide) was approved on February 7. It is the first new molecular entity approved in February for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease (CKD) on hemodialysis. It is a calcimimetic. In two randomized, double-blind, phase III controlled trials, 1023 hemodialysis patients with moderate to severe secondary hyperparathyroidism were randomized to etelcalcetide or placebo for 20 to 27 weeks, with 77% and 79% of patients in the etelcalcetide group having a 30% decrease in PTH level from baseline, compared with 11% and 11% in the placebo group, respectively; PTH levels ≤ 300 pg/mL in the etelcalcetide group were 52% and 56%, respectively, compared with only 6% and 5% in the placebo group. Previously, the FDA had rejected the product, so this product was the first to be approved by the EMA, Parsabiv is Amgen's second heavyweight secondary hyperparathyroidism drug.

▋ NO. 03 Emflaz(Deflazacort)

Emflaza(deflazacort) is a successful example of a new use of an old drug. Deflazacort is an old glucocorticoid. After the repositioning of Marathon Pharma, the dead wood is in spring. Emflaza is approved for the treatment of Duchenne muscular dystrophy (DMD) aged 5 years and older. On average, one in every 3500 newborn boys in the world suffers from this disease, and the vast majority of children will die from complications around the age of 20. DMD is a very drug-deficient area. Although the FDA approved Exondys 51 last year, the efficacy of the product has been criticized and the FDA has been pushed to the forefront. The FDA's approval of the Emflaza is based on a study done more than 20 years ago: it is difficult to say how much benefit the 196 patients have improved their muscle strength Emflaza.

▋ NO. 04 String(brodalumab)

On February 15, the FDA approved the Valeant Siliq(brodalumab) for the treatment of moderate to severe plaque psoriasis in adults who do not respond to systemic therapy or phototherapy (ultraviolet treatment), which is a second-line drug. This product is a IL-17R inhibitor, which was approved by PMDA in July last year. This product was originally developed by Amjin and later licensed to AstraZeneca and Kirin Pharmaceuticals of Japan. In May 2015, clinical data showed that brodalumab was associated with suicidal tendencies in patients, and development of the product was eventually ceded to Valente. Brodalumab is the third IL-17 antibody inhibitor. In view of the large number of competing products in this field and the suicidal tendency, it is very difficult for Brodalumab sales to reach the heavy level.

▋ NO. 05 Xermal(Telotristatetiprate)

On February 28, the FDA approved Xermelo(telotristatetiprate) for the treatment of carcinoid syndrome. Carcinoid syndrome is a group of new organisms that occur in chromaffin cells of the gastrointestinal tract and other organs, and its clinical, histochemical and biochemical characteristics may vary depending on where it occurs. Patients with carcinoid syndrome often have diarrhea without flushing of the skin, and FDA-approved Xermelo are used to suppress serotonin production and reduce the frequency of diarrhea in carcinoid syndrome.

NO. 06(ribociclib)

On March 13, FDA approved Novartis's CDK4/6 inhibitor Kisqali(ribociclib), which may be the first blockbuster drug approved in 2017. In terms of efficacy in combination with letrozole, Kisqali had a Ibrance overall response rate comparable to that of Pfizer, with a Kisqali hazard ratio of 0.556 versus 0.576 for Ibrance. Although the efficacy of ribociclib is not superior to Pfizer's same-target drug Ibrance(palbociclib), Novartis has been developing differentiated sales strategies, and the breast cancer market is so large that it is not difficult to reach the blockbuster level in the Kisqali. In the six months since its launch, this product has sold for $41 million.

Comparison of three CDK4/6 inhibitor instructions (Source: FDA)

▋ NO. 07 Xadago(safinamide)

On March 21, the FDA approved safinamide as an adjunct drug for patients who are receiving levodopa/carbidopa and are experiencing "off" episodes. After long-term treatment of general PD drugs, the control of the disease will decrease, and the phenomenon of "on-off" will appear. In the existing therapy, the addition of safinamide can effectively reduce the on-off effect. The product has been available in Europe for many years. As can be seen from Xadago on the DRUGS website (https://www.drugs.com/history/xadago.html), this product has changed hands several times and has been defeated repeatedly. Because the research and development cycle is too long, the patent protection period of this product is almost exhausted. For colleagues who do generic drugs, this is a good choice.

▋ NO. 08 Symproic(Unique))

On March 23, the FDA approved Symproic(naldemedine) for opioid-induced constipation (OIC). Naldemedine is an opioid receptor blocker that exclusively blocks peripheral opioid receptors and has little effect on central opioid receptors. The safety profile is slightly better than methylnaltrexone and naloxinone. Constipation caused by opioids is a problem that every cancer patient may encounter, but there is a risk of opioid truncation symptoms. Doctors are more cautious in prescribing, which is a major reason why the market of this kind of drugs is difficult to open. I hope the listing of this product can bring a breakthrough for OIC treatment.

▋ NO. 09 Bavencic(Avelumab)

Pfizer/Merck's PD-L1 monoclonal antibody Avelumab was approved by the FDA on March 23, 2017, becoming the first drug for second-line treatment of metastatic Merkel cell carcinoma. Results of clinical trials showed a 31.8 percent remission rate after the drug was used. Despite the approval of Merkel cell carcinoma, the main target of the Avelumab is the ovarian cancer market. It is the first checkpoint inhibitor (Checkpoint inhibitor) to enter phase III clinical trials in this indication. Currently, the development of phase III clinical trials for ovarian cancer is underway. In addition, another target of this product is gastric cancer, but unfortunately, the recently announced news shows that Bavencio(avelumab) is used as a third-line drug to treat patients with metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction (without considering the patient's PD-L1 level). There is no significant difference in improving the overall survival rate of patients compared with the chemotherapy control group. As PD-1 natural spouse, PD-L1 also has the potential to be approved in a number of cancer areas, with sales of $1.23 billion in 2021, according to the Corrividian Cortellis.

NO. 10 Zejula(Narwine))

Following AstraZeneca's Lynparza and Clovis's Rubraca, Tesaro's niraparib is the third FDA-approved PARP inhibitor. Niraparib was approved by the FDA on March 27, 2017, and is the first PARP inhibitor for maintenance therapy. In addition, Zejula does not have BRCA variation restrictions, so the applicable population is larger than the first two PARP inhibitors. Phase III NOVA trial results showed a 73% reduction in the risk of disease progression compared to placebo, with a median progression-free survival (PFS) of 21 months compared to 5.5 months for placebo. From the perspective of PFS data, the efficacy of Niraparib is remarkable. For patients with advanced cancer, few people are willing to continue chemotherapy, which brings not only a longer life span, but also a better quality of life. Given the huge advantage of niraparib, niraparib will also be one of the highlights of the 2017.

▋ NO. 11 Oct(Ocrelizumab)

Ocrevus, which received FDA approval on March 28, is the first and currently only drug in the field of MS to receive FDA breakthrough therapy. The approved indications are relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis. Ocrevus is a kind of CD20 antibody, is a new target of drugs. Based on data published in 2015, Ocrevus reached the endpoint in two pivotal trials (OPERA 1 & 2). Compared with Rebif (recombinant interferon beta-1a), the annualized relapse rate after 96 weeks of treatment was reduced by 47%. The disability progression of the disease is delayed, and the brain damage is reduced. Ocrevus is safe and well tolerated, and is the first proven effective drug for primary progressive sclerosis, reducing the risk of clinical disability progression by more than 24%. Even though the initial increase in market share may mainly come from second-line treatment for patients taking oral drugs and patients at risk of progressive multifocal leukoencephalopathy after using Tysabri (natalizumab), analysts are unanimously optimistic about the product, which will win a market of $3.327 billion in 2021, according to the Cortellis forecast of Corey Vivian.

▋ NO. 12 Dupixtes(Dupilumab)

On the same day that the FDA approved Roche's blockbuster, the FDA approved Sanofi/Regeneron's blockbuster Dupixent. Dupixent is an IL-4Rα subunit inhibitor approved on 28-Mar -2017 for the treatment of atopic dermatitis. The clinical trial SOLO-1/2 study showed that in patients with mild to moderate atopic dermatitis whose disease could not be effectively controlled by external drugs, the proportion of patients with skin lesions cleared or nearly cleared at the 16th week was 37% and 36%, respectively. Combination with corticosteroids was also superior to corticosteroids alone (39% vs 12%). Atopic dermatitis is a disease with a high incidence rate, with a lifetime incidence rate of 8-18% worldwide (Yao Xu, Pathogenesis of Atopic Dermatitis, Medicine and Pharmacy, Volume 35, Issue 68), and the potential market capacity is huge. As early as last year, Pfizer spent $5.2 billion to buy the topical drug Eucrisa was approved by the FDA, becoming the first new drug for atopic dermatitis in 15 years, but in just 3 months, the Dupixent was approved by the FDA, "both Sheng Yu, He Sheng Liang"? What kind of spark will the two grind out in this market, it is very worth looking forward.

▋ NO. 13 Austedo(Interprets rabenazine)

On April 3, the FDA approved Austedo(deutetrabenazine) for the treatment of chorea (Huntington's disease, Huntington's disease). deutetrabenazine is a deuterated product of the listed Huntington drug Tetrabenazine. Compared with the original compound, deuterated pharmacokinetic characteristics are improved and the half-life is significantly prolonged, which can reduce the therapeutic dose. Deutetrabenazine is the first deuterated drug approved by the FDA, which is favored by analysts. According to the Cortellis of Corrividian, its sales in 2022 can reach $0.485 billion.

▋ NO. 14 Raw(Valbenazine)

On April 6, the FDA approved Ingrezza(valbenazine) for the treatment of tardive dyskinesia. Tardive dyskinesia is characterized by repetitive involuntary movements, usually of the chin, lips, and tongue. Tardive dyskinesia is usually caused by phenothiazine and butyrylbenzene drugs. The incidence rate of oral common antipsychotic drugs is 20% ~ 40%, and the incidence rate of long-term antipsychotic drugs is 50%. valbenazine is the first drug approved by FDA to treat tardive dyskinesia, and it is also one of the new drugs expected to reach the heavy level.

▋ NO. 15 Brides(Cerliponase alfa)

On April 27, BioMarin Pharma's Brineura(cerliponase alfa) was approved by the FDA for the treatment of Batten's disease in children. Brineura is the first FDA-approved treatment for late-onset infantile neuronal ceroid lipofuscinosis (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency. CLN2 disease is a rare genetic disorder in which the main symptoms usually begin between the ages of 2 and 4 years and usually include delayed speech, recurrent seizures, and difficulty in coordinating movements (ataxia). Affected children can also develop conditions such as muscle twitching (myoclonus) and loss of vision. cerliponase alfa is recombinant TPP1, and patients with CLN2 disease happen to lack this important enzyme protein. In a clinical study of 22 pediatric patients with CLN2, Brineura-treated patients had reduced walking ability compared with an independent historical control group of 42 untreated CLN2 patients.

▋ NO. 16 Alunbrig(brigatinib)

On April 28, the FDA approved ALK inhibitor Alunbrig(brigatinib) for crizotinib-resistant non-small cell lung cancer. In a study of 222 patients with crizotinib resistance, the overall response rates were 48% and 53% in the brigatinib 90 and 180mg groups, respectively, with complete response rates of 3.6 and 4.5, respectively. Among patients with brain metastases at baseline, intracranial ORR was 42% and 67% in the 90 and 180mg groups, respectively. This product is accelerated approval, OS, PFS data is not yet mature, in view of the ALK positive non-small cell lung cancer patients are less, this product sales to exceed $1 billion is very difficult.

▋ NO. 17 Rydapt(Midostaurin))

On the same day that the FDA approved the brigatinib, the FDA also approved Rydapt(midostaurin), so the acute myeloid leukemia treatment drug ushered in the first new drug in 25 years. Raydap is also the first targeted therapy that can be combined with chemotherapy to treat acute myeloid leukemia for FLT3 positive patients with acute myeloid leukemia. It is estimated that patients with acute myeloid leukemia with mutations in the FLT3 gene account for one third of the total number of patients with the disease. Seventeen FLT3-positive patients with treatment-naive acute myeloid leukemia entered the trial, and data showed that patients who received the chemotherapy + Raydap combination had a significant improvement in overall survival and a 23% lower risk of death compared with patients who received chemotherapy alone.

▋ NO. 18 Tymlos is a former professional footballer who plays as a teacher.(abaloparatide)

On April 28, the FDA also approved Tymlos(abaloparatide) for the treatment of postmenopausal osteoporosis in women. abaloparatide is an analog of parathyroid hormone-related protein (PTHrP), which can bind to parathyroid receptor 1 to regulate metabolism and promote bone formation. In the ACTIVE clinical trial (18-month data) and the ACTIVExtend clinical trial (first 6-month data), abaloparatide reduced the risk of new vertebral fractures by 86% and non-vertebral fractures by 43% compared with placebo. In addition, the absolute risk of new vertebral and non-vertebral fractures was reduced by 3.6 and 2.0, respectively.

▋ NO. 19 Description(Horribmab)

Imfinzi(durvalumab) received accelerated approval from the FDA on May 1 for the treatment of metastatic bladder cancer and is the third PD-L1 inhibitor. Metastatic bladder cancer is a type of bladder cancer with a poor prognosis, with a 5-year survival rate of less than 15%, and no significant progress has been made in the past 30 years. Durvalumab is a drug recognized as a breakthrough therapy. ASCO public data show that the overall objective response rate (ORR) of Durvalumab therapy is 31%, of which 46% are for patients with high PD-L1 expression, 48% are for disease control rate (DCR), and 57% are for patients with high PD-L1 expression. While this drug could provide a meaningful treatment option for bladder cancer, it is AstraZeneca's goal to take the market for lung cancer. At present, the key three phases of the first-line therapy for lung cancer of this product are still in development. The success of this product will determine the fate of this product. According to the Cortellis forecast of Corey Vian, the product can win a market of 2.056 billion US dollars in 2021.

▋ NO. 20 Radicals(Edaravone)

On May 5, the FDA approved edaravone for the first time for the treatment of amyotrophic lateral sclerosis (ALS). ALS is commonly known as gradual freezing disease, when the "ice bucket challenge" brought the disease into people's vision. There is almost no specific drug treatment for ALS. The FDA previously approved riluzole, but it can only increase the one-year survival chance by about 10%. At the annual meeting of the American Society of Neurology, Mitsubishi Tanabe presented the results of a phase III clinical trial of his ALS drug Edaravone. The addition of Edaravone to standard therapy significantly improved the ALSFRS-R of comprehensive functional indicators in ALS patients (-5.0 versus -7.5), as well as local functions such as exercise and respiration. Edaravone has been approved for ALS in Japan in South Korea. As early as last year, Mitsubishi Tanabe submitted an NDA to the US FDA and obtained orphan drug status.

NO. 21 Kevzara(sarilumab)

On May 22, FDA approved the IL-6R monoclonal antibody Kevzara(sarilumab) jointly developed by Sanofi/Regeneron. As early as the beginning of the year, this product has been approved by the Canadian Health Bureau. It is the second listed 1L-6R monoclonal antibody in the world after Roche Actemra. It is used for adult patients with moderate to severe active rheumatoid arthritis who do not fully respond to or tolerate one or more biological or non-biological disease-modifying antirheumatic drugs (DMARDs). In the post-adalimumab era, IL-6R monoclonal antibody and JAK inhibitor will definitely become the main force of the wind-like barrier. However, there are many products in this field, and it is still very difficult for this product to reach the heavy level. However, Sanofi is already very lucky compared with Johnson & Johnson, which encountered "Waterloo" (FDA rejected its IL-6R monoclonal antibody sirukumab).

NO. 22 Buffalo.(delafloxacin)

Baxdela(delafloxacin) was approved by the FDA on June 19. It is a new generation of quinolone antibiotics for the treatment of acute bacterial skin and skin structure infections caused by susceptible bacteria. It is more effective against gram-positive bacteria than other quinolone antibacterial agents, especially methicillin-resistant Staphylococcus aureus (MRSA) resistant to other quinolone antibacterial agents. In two Phase III clinical trials, both intravenous and oral delafloxacin were evaluated for non-inferiority compared with intravenous vancomycin aztreonam at the FDA's primary endpoint of 48-72 hours. In addition, Delafloxacin had lower side effects, and no QT prolongation or phototoxicity was shown in clinical trials, nor was there any adverse effect on liver and kidney function.

NO. 23 Bevyxxa(betrixaban)

On June 23, the FDA approved Bevyxxa(betrixaban),betrixaban a once-daily oral factor Xa inhibitor with the same mechanism of action as rivaroxaban and apixaban. The FDA approved its use in patients with long-term hospitalization or venous thromboembolism due to limited exercise. Controversially, the new drug did not meet the primary clinical endpoint in the target population. In a large phase III trial that enrolled 7513 patients hospitalized for severe symptoms worldwide, patients receiving Betrixaban (6-14 days placebo +35-42 days placebo) had a reduced proportion of venous thromboembolism compared with patients treated with enoxaparin (6-14 days enoxaparin plus 35-42 days betrixaban), but 6.9 percent of the Betrixaban group compared with 8.5 percent of the enoxaparin group in the primary target population, there was no statistical difference.

▋ NO. 24 Tremfya(See section 4.4))

On July 13, the FDA approved Johnson & Johnson's Tremfya(guselkumab) for adult patients with moderate to severe plaque psoriasis who are eligible for systemic therapy (injectable or oral therapy) or light therapy (UV therapy). Recently, this product has been approved by EMA, becoming the first and only monoclonal antibody approved in Europe only for interleukin-23 (IL-23). Tremfya approval was based on data from a Phase III clinical program that included three Phase III studies (VOYAGE 1, VOYAGE 2, and NAVIGATE) involving more than 2000 patients. VOYAGE 1 and VOYAGE 2 evaluated the efficacy and safety of Tremfya versus placebo and Humira (adalimumab), and NAVIGATE evaluated the efficacy and safety of Tremfya versus Stelara(ustekinumab). In the two studies, 73.3 and 70.0 percent of patients in the Tremfya treatment group achieved PASI90 remission at week 16, and 49.7 and 46.8 percent of patients in the Humira treatment group achieved PASI90 remission, respectively. The results from the NAVIGATE study confirm that Tremfya has a significant effect in patients who have previously had an inadequate response to Stelara therapy.

▋ NO. 25 Nern(neratinib)

On July 17, the FDA approved Nerlynx(neratinib) for extended adjuvant therapy for early HER2-positive breast cancer, which is suitable for adult patients who have received previous treatment with trastuzumab to reduce the risk of breast cancer recurrence. Standard review means that this product does not have such excellent breakthrough curative effect as Ibrance, but its combination with trastuzumab can significantly prolong the DFS of breast cancer. Considering the huge market of breast cancer, this product will also be one of the selling points. According to the Cortellis of Corey Weian, the sales revenue of this product in 2022 is predicted to reach 1.656 billion US dollars, which is a real blockbuster product.

▋ NO. 26 Vosevi (sphosbuvir), Velpatasvir, Voxilaprevir)

On July 18, the FDA approved Giledad's hepatitis C three-generation cocktail for retreatment of adult patients with hepatitis C (HCV) of all six genotypes who had previously failed to receive a regimen containing an NS5A inhibitor. Vosevi(Voxilaprevir velpatasvir voxilaprevir) is a three-in-one therapy. Compared with Harvoni, the curative effect has been improved, but there is little room for improvement, because Harvoni curative effect is already very good. Although Vosevi is not as eye-catching as previous generations of cocktails, it has sold for US $0.123 billion in the past about two months. It is also a DingTalk on the iron plate to become a blockbuster product. According to the Cortellis forecast, the sales of this product in 2021 will be 1.103 billion US dollars.

▋ NO. 27 Ideas(Enasidenib)

On August 1, the FDA approved Idhifa(Enasidenib) for the treatment of IDH2-mutated acute myeloid leukemia (AML). IDH2 positive patients only account for 8% to 19% of all AML patients. Therefore, this product has been qualified for priority review and orphan drug identification. Idhifa is an IDH2 (isocitrate dehydrogenase) inhibitor and the first oncogenic metabolite synthesis inhibitor on the market. Idhifa has been studied in a single-arm test of 199 relapsed or refractory AML patients for 6 months, there was a complete response in 19% of patients, with a median response time of 8.2 months, and 4% of patients had complete remission with partial hematologic recovery, with a median survival time of 19.7 months.

▋ NO. 28 Mavy (capture), Pybrentasvir)

On August 3, FDA approved AbbVie's 8-week course of full genotype hepatitis C cocktail Mavyret, which consists of NS3/4A protease inhibitor glecaprevir(100mg) and NS5A inhibitor pibrentasvir(40mg). Published clinical data show that the virological cure rate (SVR12) of Mavyret 8-week treatment regimen in patients without liver cirrhosis and patients with newly diagnosed genotype 1-6 hepatitis C reached 97.5%(n = 693/711); in patients with genotype 1-6(GT 1-6) hepatitis C with severe chronic kidney disease (CKD), virological cure rates reached 100%(n = 102/102) Mavyret the 12-week regimen. AbbVie Q3's financial report showed that its Q3 HCV revenue was only US $0.216 billion, of which US $0.06 billion. The approval of the Mavyret is expected to help AbbVie recover from the losing hepatitis C market. According to the Cortellis forecast of Corey Vian, the sales volume of this product will reach 1.002 billion US dollars in 2022.

▋ NO. 29 Watching the World(Inotuzumab ozogamicin)

On August 17, the FDA approved Pfizer's Besponsa(inotuzumab ozogamicin) for the treatment of adults with relapsed or refractory B- cell precursor acute lymphoblastic leukemia (ALL). Besponsa is an antibody drug conjugate (ADC) of CD22 antibody and ozogamicin. The B- cell precursor ALL is a progressive malignancy in which the bone marrow produces too many beta lymphocytes, a type of immature white blood cell. The National Cancer Institute estimates that about 5970 people in the United States have been diagnosed with B- cell ALL this year, and about 1440 people have died from the disease. In a randomized trial of 326 patients with relapsed or refractory beta-cell ALL who had received one or two previous treatments, 35.8 percent of patients treated with Besponsa had a median of 8.0 months of complete remission, compared with 17.4 percent of patients treated with other chemotherapy.

▋ NO. 30 tons of clouds)

On August 29, the FDA granted accelerated approval of benznidazole (benznidazole) for the treatment of patients 2 to 12 years of age with Chagas disease (Chagasdisease). Chagas disease, a parasitic infection caused by trypanosoma cruzi (Trypanosoma cruzi), can be transmitted by different routes, affecting about 300000 people in the United States. Clinical trial data showed that the proportion of children taking benznidazole antibody tests from positive to negative was 60%, compared with 14% in the placebo group. The results of another trial were similar, with about 55% of children taking benznidazole antibody tests turning negative, compared with 5% in the placebo group.

NO. 31 From Our Archives,Vaborbactam)

Also on August 29, the FDA also approved the Vabomere for the treatment of patients with complicated urinary tract infections (cUTI), which includes pyelonephritis caused by specific bacterial infections. Vabomere is a combination formulation consisting of the approved drug meropenem and a new beta-lactamase inhibitor Vaborbactam. In a clinical trial of 550 adult patients, patients were randomized 1:1 to 10 days of Vabomere therapy or standard control therapy. The results showed that the improvement of symptoms in the Vaborbactam group was higher than that in the control group (95% CI:0.3-8.8).

NO. 32 “Be Hospitable ”(Copanliyib)

On September 14, the FDA approved the Bayer PI3K inhibitor Aliqopa(Copanlisib) for the treatment of adult patients with follicular lymphoma who have relapsed after more than 2 systemic treatments. In 104 patients with follicular B- cell non-Hodgkin lymphoma who had relapsed after more than two previous treatments, the overall response rate was 59%. The median duration of remission in patients with complete or partial remission was 12.2 months. Copanlisib is another PI3K inhibitor approved after the Gilded Idelalisib, and the FDA has granted accelerated approval and orphan drug status due to its excellent efficacy and scarcity of patients.

NO. 33 Solosec(Secnidazole)

On September 15, the FDA approved Symbiomix's Solosec(secnidazole) for the treatment of vaginitis in adult women. secnidazole, a 5-nitroimidazole antibiotic, is the only single-dose oral treatment for bacterial vaginosis. In clinical trials, after 21-30 days of treatment with either Bentone or placebo, clinical response rates were 67.7 percent and 53.3 percent, respectively, for trial 1. and trial two, compared with 17.7 percent and 19.3 percent for placebo under the same conditions. Bacterial vaginosis is the most common gynecological infection in the United States, affecting 21 million women between the ages of 14 and 49 each year, so this product has good market prospects.

▋ NO. 34 Verzenio ( abemaciclib)

On September 28, FDA approved the third CDK4/6 inhibitor Verzenio(abemaciclib). With the approval of the Verzenio, the "Romance of the Three Kingdoms" of CDK4/6 in the United States was officially staged. In terms of curative effect, 19.7% of the 132 HR + and HER2-patients whose cancer still progressed after endocrine therapy and chemotherapy received Verzenio monotherapy experienced complete remission (CR) or partial remission (PR), with a median objective remission time of 8.6 months. The median progression-free survival (PFS) of 16.4 months in combination with fulvestequant was higher than that of placebo and fulvestequant (9.3 months). In terms of combined fulveyor treatment, from the patient's progression-free survival and overall response rate data, Verzenio is slightly better than Ibrance, with a hazard ratio of 0.556, while Ibrance is 0.461. But for the late Verzenio, the situation is very unfavorable, because Pfizer has occupied half of the breast cancer market in the United States. If there is no differentiated sales, it will be difficult for this product to stand out. However, fortunately, the breast cancer market is huge, and Verzenio can also get its share of the pie. It should not be very difficult to reach the blockbuster level. According to the Cortellis of Corey, the sales volume of this product in 2022 can reach 1.721 billion US dollars.

NO. 35 Calquence(Acalabrutinib)

On October 31, the FDA accelerated approval of AstraZeneca's BTK inhibitor Calquence(acalabrutinib) for adult patients with mantle cell lymphoma (MCL) who have received at least one prior treatment. The approval of the Bruton tyrosine kinase (BTK) selective inhibitor acalabrutinib was based on data ACE-LY-004 MCL, a phase 2 open-label, single-arm clinical trial in 124 adults with relapsed or refractory MCL. In the trial, 81% of patients achieved partial or complete remission, with a complete remission rate of 40% and a partial remission rate of 41%. According to Corey Vian Cortellis, sales of this product will reach US $0.988 billion in 2022.

NO. 36(Latanoprostene bunod)

On November 2, the FDA approved the new anti-glaucoma drug Vyzulta(latanoprostenebunod). This product has a dual mechanism of action, latanoprost acid (latanoprost acid) can act on the uveoscleral pathway to promote the discharge of aqueous humor; butanediol mononitrate (butanediol mononitrate) can release nitric oxide through the trabecular meshwork and Schlemm's canal (Schlemm's canal) to promote the discharge of aqueous humor. Compared with timolol maleate eye drops, Vyzulta showed non-inferiority and superiority; compared with latanoprost, Vyzulta reduced intraocular pressure more significantly.

▋ NO. 37 Prevymis (framework)

On November 8, FDA approved Merck's new drug Prevymis(letermovir) for the prevention of cytomegalovirus (CMV) infection and related diseases in adult patients who are seropositive after allogeneic hematopoietic stem cell transplantation (HSCT). The approval of the Prevymis was based on data from a pivotal phase III clinical study. Compared with the placebo group, the proportion of patients with clinically significant CMV infection, discontinuation of treatment, or missing data at week 24 after HSCT was significantly reduced in the Prevymis treatment group (-23.5%,-14.6%,), and the primary endpoint was met. At 24 weeks after transplantation, all-cause mortality was lower in the Prevymis group than in the placebo group (12% vs 17%). Revymis is the first new drug approved for CMV infection in the United States in 15 years. It is a non-nucleoside CMV inhibitor that inhibits viral replication by targeting the viral termination enzyme (terminase) complex.

▋ NO. 38 Photo(benralizumab)

On November 14, the FDA approved the marketing of AstraZeneca Fasenra(benralizumab) for additional maintenance therapy for severe asthma patients 12 years of age and older with an eosinophilic phenotype. There are about 0.32 billion asthma patients in the world, and only about 10% of them are severe asthma. However, there is still a great unmet demand for treatment in clinical practice. Previously, FDA approved Roche's Xolair(Omalizumab), GSK's Nucala(Mepolizumab) and Teva's Cinqair(Reslizumab). This product is already the fourth approved product, and there are also potential competitors under research. AstraZeneca wants to break out of the tight encirclement and reach a heavy level, with many difficulties. In terms of clinical efficacy, SIROCCO and CALIMA clinical trials have shown that benralizumab can reduce the annual incidence of acute exacerbations of asthma by 51% after four weeks of continuous medication. Compared with oral glucocorticoids in the placebo group, benralizumab significantly reduced the mean oral glucocorticoid dose from baseline to the end (by 75%).

NO. 39 Mapsvii(Vestronidase alfa-vjbk)

On November 15, the FDA approved Mepsevii Ultragenyx Pharma (vestronidase alfa-vjbk) for the treatment of mucopolysaccharidosis type VII (MPS VII). Mucopolysaccharidosis is a rare disease, and there are multiple subtypes, type VII is the rarest one, the incidence rate is less than one in a million. In terms of efficacy, in a clinical trial involving 23 patients, the age of the patients ranged from 5 months to 25 years old, and the Mepsevii was used for 164 weeks. The results showed that after 24 weeks of treatment, the 6-minute walking test results of the treatment group were 18 meters more than that of the control group. In a follow-up of up to 120 weeks, the researchers found that the condition of three patients continued to improve, and the remaining patients who could participate in the walking test also stabilized their condition.

▋ NO. 40 Hemlibra(emicizumab)

On November 16, FDA approved Roche's leukemia monoclonal antibody Hemlibra(emicizumab), which is the first new drug approved by FDA in the past 20 years for the treatment of hemophilia A containing factor VIII inhibitor. In 2015, Hemlibra was granted priority accreditation and breakthrough therapy recognition by the FDA, and this approval is based on the results of two clinical trials. The HAVEN1 study showed that haemophilia A patients 12 years of age and older who had factor VIII inhibitors in their bodies had an 87% reduction in bleeding rates after receiving Hemlibra prophylaxis compared with patients who did not receive prophylaxis. The first within-patient analysis of its kind showed a significant 79% reduction in bleeding rates in patients receiving BPA prophylaxis compared with patients receiving Hemlibra prophylaxis in a non-interventional study (NIS). The interim results of the HAVEN2 study show that 87% of children under 12 years of age with hemophilia A containing inhibitors did not experience bleeding after receiving Hemlibra preventive treatment. In a within-patient analysis of 13 pediatric patients enrolled in NIS, Hemlibra prevention treatment reduced bleeding rates by 99% compared with BPA treatment.

▋ NO. 41 Ozempic (Smoking)

The most anticipated new drug in December is Semaglutide, which was approved by FDA on December 5, according to Novo Nordisk's official website. Semaglutide and liraglutide are GLP-1 analogs, but the administration period is longer than liraglutide, and the efficacy is not inferior to liraglutide. Early published clinical data showed that the therapeutic effects of Semaglutide(0.5mg/1.0mg) and Trulicity(0.75mg/1.5mg) at the two doses Semaglutide showed hypoglycemic advantages. The values for the Semaglutide patient group were 1.5 and 1.8 percent for the two doses, respectively, and 1.1 and 1.4 percent for the Trulicity. At the same time, the weight loss effect of Semaglutide was also excellent. Clinical data showed that the average weight loss of Semaglutide treatment patients was 6.5kg, while the Trulicity was only 3.0kg. In addition, Semaglutide is the second GLP-1 analog, after liraglutide, to be shown to reduce the risk of heart failure. Data from the clinical study were made public at the EASD Annual Meeting on September 16, 2016. Novo Nordisk is not satisfied with winning the above title. It also plans to start the study of the large cardiovascular outcome of Somaglutide 12500-in order to maintain its dominant position in the field of GLP-1, Novo Nordisk has really fought! However, this product is unanimously favored by investors and is one of the highlights of the 2017. Cortellis analysts predict that the product is expected to win sales of US $1.938 billion in 2021, ranking fourth among the most noteworthy drugs in 2017.

▋ NO. 42 Macrilene(macimorelin)?

New drugs with PDUFA deadlines falling in December include Ataluren, Macimorelin and ertugliflozin. Ataluren have received a response from the FDA, and the answer is to deny approval. The PDUFA deadline for Macrilen(macimorelin) is December 30, 2017. It is a growth hormone receptor agonist and is indicated for adult growth hormone deficiency (AGHD). Aeterna Zentaris submitted NDA to FDA as early as 2013, and FDA rejected it with insufficient evidence of efficacy. Later, the company launched a new clinical trial and submitted NDA to FDA again on June 30.

▋ NO. 43 ErtugliflozineWhat?

Ertugliflozin, which is also a hypoglycemic drug with Semaglutide, is an SGLT2 inhibitor. Its PDUFA is until December 31, but it is much inferior to the Semaglutide, because it is already the seventh SGLT2 inhibitor in the world, and it is similar to entogliflodin. Compared with caglifloin and canagliflodin, it did not show obvious advantages. However, Mercadon has the heavy oral hypoglycemic drug sitagliptin, and Ertugliflozin is positioned to take a ride on sitagliptin. In the 26-week VERTIS SITA study, Ertugliflozin 5mg or 15mg in combination with sitagliptin 100mg reduced blood glucose better than placebo, resulting in a 1.6 and 1.7 percent reduction in HbA1c, respectively, compared with 0.4 percent in the placebo group (p<0.001). In the 26-week VERTIS MET study, 5mg or 15mg of Ertugliflozin combined with metformin reduced blood glucose better, with HbA1c reduced by 0.7 and 0.9, respectively, compared with 0.0 in the placebo group (p<0.001).

List of new drugs already approved by the FDA