Chemical entities SHINE in the top 10 fastest-growing drugs of 2016

Global pharmaceutical companies are increasingly focusing on the development of new biologics. In fact, in 2016, nine out of the top 15 pharmaceutical drugs by sales were of biologic origin. This makes us wonder what the future holds for manufacturers specializing in drugs that originate from chemical synthesis.

This week, PharmaCompass continued its analysis of the top pharma drugs by sales to evaluate the drugs that registered large sales growth in 2016.

Please note that these are not the top-selling drugs, but are the top 10 drugs that registered the maximum growth in global sales over 2015.

Interestingly, things didn’t appear that bad for drugs originating from chemical synthesis — while the top two drugs on the list were biologics, the remaining originated from chemical synthesis.

Here’s a list of drugs that witnessed the largest sales growth in 2016:

1. Opdivo (nivolumab) – Bristol-Myers Squibb

2016 sales: US$ 3,774 million

2015 sales: US$ 942 million

Sales growth: US$ 2,832 million

First approved in 2014, Bristol-Myers Squibb’s Opdivo and Merck’s Keytruda — also known as checkpoint inhibitors — continued to stay on track to be among the top 20 best-selling drugs in the world by 2020. They represent the hot new field of immunotherapy and are known to have given 90-year old Jimmy Carter (former President of the United States) hope in his fight against cancer.

With a sales growth of US$ 2.832 billion, Opdivo registered the highest sales growth of any single drug in 2016. However, Bristol-Myers Squibb received a nasty surprise last year when Opdivo did not demonstrate the desired slowdown in the progress of advanced lung cancer in a trial, as compared to conventional chemotherapy.

While Bristol-Myers’ stock price plunged on this news, Merck announced that not only did Keytruda succeed in a clinical trial as an initial treatment for advanced non-small cell lung cancer, but patients actually lived longer. Although Keytruda did not make it to our list of top 10 drugs by sales growth in 2016, it did register a sales increase of US$ 836 million, as its sales grew from US$ 566 million to US$ 1,402 million.

2. Humira (adalimumab) – AbbVie

2016 sales: US$ 16,078 million

2015 sales: US$ 14,012 million

Sales growth: US$ 2,066 million

Abbvie’s Humira (adalimumab) juggernaut continued as it not only remained the best-selling drug in the world, but also added another US$ 2 billion to its 2015 sales by generating record sales of US $16.078 billion in 2016.

Last year, the US Food and Drug Administration (FDA) approved Amgen’s Amjevita™ (adalimumab – atto) — a biosimilar of Humira®. Therefore, it remains to be seen if Humira will be able to sustain the momentum. Amjevita was approved for treating adults with a variety of medical conditions ranging from rheumatoid arthritis, plaque psoriasis, to ulcerative colitis.

3. Epclusa (sofosbuvir and velpatasvir) – Gilead

2016 sales: US$ 1,752 million (new launch)

Gilead’s third sofosbuvir-based regimen — Epclusa (sofosbuvir and velpatasvir) was approved by the US FDA in June 2016. It is the first and only all-oral, pan-genotypic single tablet regimen for chronic Hepatitis C virus infection. While Epclusa registered an impressive start, Gilead’s other two sofosbuvir-based treatments — Sovaldi (sofosbuvir) and Harvoni (sofosbuvir and lepidasvir) — saw their combined sales decline by almost US$ 6 billion.

4. Imbruvica (ibrutinib) — Johnson & Johnson / AbbVie

2016 sales: US$ 3,083 million

2015 sales: US$ 1,443 million

Sales growth: US$ 1,640 million

Abbvie’s 2015 US$ 21 billion buy of Pharmacyclics seems to be paying off. The Pharmacyclics buy was a way to get access to Imbruvica (ibrutinib), a cancer drug which is co-marketed with Johnson & Johnson. It generated sales of US$ 3.083 billion in 2016. Imbruvica works by blocking a specific protein called Bruton’s tyrosine kinase (BTK). In December 2011, Johnson & Johnson said it would pay Pharmacyclics as much as US$ 975 million to fund getting the drug to market in exchange for half the profits generated globally.

5. Eliquis (apixaban) – Bristol-Myers Squibb / Pfizer

2016 sales: US$ 3,342 million

2015 sales: US$ 1,860 million

Sales growth: US$ 1,483 million

Although apixaban was the third-to-market novel oral anticoagulant (NOAC), which is co-promoted by Pfizer and Bristol-Myers Squibb as Eliquis, it continues to unseat Johnson & Johnson’s Xarelto (rivaroxaban) as the leader in its class based on total prescriptions. Rivaroxaban’s total 2016 sales were US$ 5.392 billion.

While Pfizer’s reports its sales as part of Alliance revenues, and exact sales are not known, Bristol-Myers Squibb results alone put Eliquis in the top 10 list. Generics are hot on their tail as, last month, Pfizer and Bristol-Myers’ filed suits against 16 generic makers to uphold their patents for apixaban.

6. Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) — Gilead

2016 sales: US$ 1,484 million

2015 sales: US$ 45 million

Sales growth: US$ 1,439 million

Genvoya has been the most successful HIV treatment launch since the introduction of Atripla (the first single-tablet regimen launched a decade ago). Gilead is the dominant HIV player in the US market and has the top three most-prescribed HIV regimens in the US.

Genvoya adds Tenofovir Alafenamide (TAF) to already known treatments. TAF based drugs have demonstrated a better safety profile. They would also allow Gilead to maintain its dominance in the HIV market.

7. Ibrance (palbociclib) — Pfizer

2016 sales: US$ 2,135 million

2015 sales: US$ 723 million

Sales growth: US$ 1,412 million

Discovered in Pfizer laboratories and approved by the US FDA in February 2015, Ibrance is used in combination with Letrozole as a first-line treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer.

8. Triumeq (abacavir, dolutegravir, lamivudine) – GlaxoSmithKline

2016 sales:US$ 2,151 million

2015 sales: US$ 905 million

Sales growth: US$ 1,246 million

GlaxoSmithKline’s HIV drugs business — ViiV Healthcare — has been enjoying sales growth with the introduction of Triumeq ® in its portfolio. While GSK is the major shareholder in ViiV Healthcare, Pfizer and Shionogi also have a stake. Triumeq® is the company’s first fixed-dose combination tablet for a once-daily single pill regimen that combines dolutegravir, an integrase inhibitor, with the nucleoside reverse transcriptase inhibitors — abacavir and lamivudine.

9. Revlimid (lenalidomide) – Celgene

2016 sales: US$ 6,974 million

2015 sales: US$ 5,801 million

Sales growth: US$ 1,173 million

Celgene’s Revlimid (lenalidomide) — a thalidomide-derivative introduced in 2004 as an immunomodulatory agent for the treatment of various cancers such as multiple myeloma — brought in US$ 5.8 billion in 2015, and grew another 20 percent this year, to US $6.974 billion. Revlimid now contributes more than 60 percent to Celgene’s total sales of US$ 11.229 billion.

10. Xarelto (rivaroxaban) – Johnson & Johnson (US) and Bayer

2016 sales: US$ 5,392 million

2015 sales: US$ 4,255 million

Sales growth: US$ 1,137 million

Bayer’s Xarelto, which is promoted by Johnson & Johnson in the United States, provided patients with an alternative to the old-guard therapy — warfarin. While rivaroxaban is competing with other novel oral anticoagulants (NOAC) like Eliquis (apixaban) and Pradaxa (dabigatran), rivaroxaban has the class lead in indications.

Xarelto recently posted positive results in a large-scale Phase 3 study —COMPASS, involving 27,402 patients, that assessed the effect of the blood thinner in preventing major adverse cardiac events (MACE).

The trial was stopped a year early on the advice of an independent Data Monitoring Committee, after the primary endpoint of prevention of MACE (which includes cardiovascular death, myocardial infarction and stroke) reached its pre-specified criteria for superiority over aspirin.

Our view

In QuintilesIMS Institute’s new annual drug spending report, analysts have forecasted that over the coming five years the industry should continue to receive 40 to 45 new drug approvals every year.

A quarter of all the drugs in late-stage development are now focused on oncology. The rate of oncology drug development has hit such a rapid pace that new drugs are superseding old ones in a matter of a few years.

It’s clear that this compilation will see radical changes next year. However, with eight out of the 10 fastest-selling drugs coming from chemical synthesis, traditional generic manufacturers still have a lot of opportunities to explore.

 

Article credit: https://www.pharmacompass.com/radio-compass-blog/chemical-entities-shine-in-the-top-10-fastest-growing-drugs-of-2016

Tadalafil Tested as Possible Dementia Therapy

tadalafilThe close of 2014 brought exciting news for patients suffering from dementia with the announcement that Tadalafil, a commonly used drug that treats erectile dysfunction, is being tested as a treatment for dementia. The Alzheimer’s Drug Discovery Foundation and the Alzheimer’s Society UK shared the news of their partnership and funding, which would be earmarked for studying Tadalafil as a potential treatment to combat vascular dementia. This is the first study to be done using an erectile dysfunction (ED) drug as a possible therapy for dementia, and plans are underway to create a cross-Atlantic project. One goal set at the G8 summit on dementia was to ascertain a disease-modifying treatment for this devastating disease by 2025, which is now a decade away. Scientists from St. George’s University of London will be spearheading this research, going on the premise that the ability of Tadalafil to increase blood flow will translate to greater blood flow to the brain, thus combating vascular dementia. The study will begin by recruiting 50 patients, all over age 65 who have displayed blood vessel damage, also known as small vessel disease. The patients will also need be documented as experiencing at least mild memory loss. The research will be measured by testing the blood flow to the brain via an arterial spin labelling MRI. Both a Tadalafil and placebo group are planned for this novel study.

ASLAs the second most common form of dementia in America, a diagnosis of vascular dementia is most often caused by brain damage to small blood vessels, leading to a reduction in blood flow to brain tissue. Affecting over one million adults in the United States vascular dementia is diagnosed most often in elderly people. A diagnosis of mixed dementia usually includes vascular dementia, and is found in up to 70 percent of elderly people over age 80. With drug research taking one to several decades to complete, the commencement of this study is exciting as a real possibility for the growing aging population. In the United Kingdom vascular dementia is considered to be the most common form of dementia, accounting for 110,000 cases yearly.

As a carboline-based compound with vasodilatory activity, Tadalafil is an effective inhibitor of the cyclic guanosine monophosphate, resulting in vasodilation, as well as muscle relaxation. The successful of Tadalafil, known as the brand name drug Cialis, has been documented for patients around the world suffering from erectile dysfunction.

LGM Pharma can assist clients as a supplier/distributor of the TEVA API Tadalafil, CAS # 171596-29-5 for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e) +A13(1). Any patent infringement and resulting liability is solely at buyer risk.

 

Clopidogrel Continues to Prove Its Safety and Efficacy

Clopidogrel Bisulfate TEVA APIClopidogrel Bisulfate, also known as the brand name anticoagulant medication Plavix, continues to impress with its safety profile. A study released at the end of March 2013 revealed that patients set to undergo percutaneous coronary intervention could successfully continue their regimen of Clopidogrel during this time. Caution was extended from the study investigators, which took place in Belgium and the Netherlands, stressing that aspirin should not be continued with this treatment plan. The study set out to determine if the use of Clopidogrel either with or without aspirin was safe and tolerable for patients expecting to have a percutaneous coronary intervention. This trial was an open-label, controlled and randomized study that involved 573 patients. During a one year period of time 279 patients were administered Clopidogrel and 284 patients were given Clopidogrel and aspirin therapy. Unusual bleeding episodes were recorded in approximately 54 of the patients who received treatment with Clopidogrel only. In the group of participants that were administered Clopidogrel and an aspirin regimen there were 126 patients who experienced adverse bleeding episodes. The need for blood transfusions was low for the Clopidogrel only group, with 11 patients needing this life saving intervention. Of the participants in the group who were dosed with aspirin and Clopidogrel there were 27 patients who ended up needing a blood transfusion.

The bottom line of this study revealed that the use of Clopidogrel without aspirin was safe, tolerable, and showed a sizable reduction in complications from bleeding. Positive news was also gleaned from the study regarding thrombotic events, as the use of Clopidogrel without aspirin did not augment the instance of additional thrombotic events. The patent for Plavix, the brand of Clopidogrel, expires on June 10, 2019.

LGM Pharma provides Clopidogrel as a TEVA API, CAS number 144077-07-6, for research and development purposes. Clients can be assured of quality API products and continuous support throughout the R&D process.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Tadalafil Alongside Finasteride Once Daily Improved IPSS For Men

European Association of Urology CongressTadalafil, also known as Cialis, is making headlines in pharmaceutical news. A study released on March 18, 2013 touted the use of tadalafil alongside finasteride for sizably improving scores for men on the International Prostate Symptom Score. Marketed by Eli Lilly, the patent for Cialis expires on November 21, 2017. The study, which was revealed at the European Association of Urology Congress in Milan, showed that five milligrams of tadalafil {Cialis} administered alongside finasteride once daily significantly improved the scores for men on the International Prostate Symptom Score. These men had lower urinary tract symptoms of benign prostatic hyperplasia and enlarged prostates. Additionally, the co-administration of tadalafil and finasteride improved the erectile function scores in these men, who had both lower urinary tract symptoms of benign prostatic hyperplasia and erectile dysfunction at baseline. Both studies compared the once daily use of tadalafil and finasteride to finasteride and a placebo.

Currently approved by the FDA to treat the signs and symptoms of both benign prostatic hyperplasia and erectile dysfunction, tadalafil is proving to be successful. Finasteride is currently approved by the FDA for the treatment of men with benign prostatic hyperplasia with an enlarged prostate. The aforementioned study was comprehensive, and involved 696 men ages 45 and older. All of the men had an International Prostate Symptom Score of at least 13, a urine flow rate of 4 millimeters per second to 15 mL/sec and a prostate volume at least 30 mL. Results revealed that the primary endpoint was met regarding improved International Prostate Symptom Scores {IPSS}. The IPSS scores showed meaningful improvements through the 12 week study. The scores at 12 weeks significantly improved IPSS scores, specifically -5.2 for the tadalafil and finasteride group versus the placebo/finasteride at -3.8. The daily dose of tadalafil and finasteride also greatly improved the men’s IPSS total scores versus the placebo/finasteride at 4 weeks, specifically -3.9 versus -2.3. Finally, the 26 week mark also rendered a cogent result, with IPSS total scores of the tadalafil and finasteride treatment versus the placebo/finasteride being -5.5 versus -4.5.  With mild side effects such as headache, indigestion and back pain, results from this study appear to show the tadalafil and finasteride drug combination to be safe, efficacious and generally tolerable.

LGM Pharma provides TEVA API tadalafil, CAS number 171596-29-5, as well as finasteride, CAS number 98319-26-7 for research and development purposes. Clients can be assured of continuous support throughout the R&D process, as well as quality API products.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.

Alogliptin Shines in Three Recent FDA Approvals

Alogliptin is a current newsmaker in the pharmaceutical industry. On January 25, 2013 Takeda announced that Alogliptin, CAS# 850649-62-6, was approved alongside Metformin HCl, CAS# 1115-70-4, in the novel type 2 diabetes medication Kazano. As an efficacious and highly selective DPP-4 inhibitor, Alogliptin, when combined in this single dose tablet with metformin HCI effectively aids patients, alongside dietary and lifestyle changes. The easy once a day dosing schedule, in one tablet, makes Kazano a preferable choice for many patients. Adverse effects of Kazano may include upper respiratory tract infections, mild diarrhea, headache and mild back pain.  For many patients with type 2 diabetes the side effects are outweighed greatly by the benefits of this dynamic combination of alogliptin and metformin. Metformin has been a gold standard member of the biguanide class of medications, and it is typically a first-line therapy in addition to diet and exercise for patients with type 2 diabetes. The addition of alogliptin with metformin makes for a formidable combination, by helping to regulate blood glucose levels and improve pancreatic beta-cell function.

“The FDA approved these three formulations of alogliptin, to be taken alongside a dietary and exercise program to control type 2 diabetes.”

The FDA approval of Kazano was based on positive findings from the clinical trials of alogliptin and metformin, which involved over 4,000 patients.  Results from studies showed that when alogliptin was administered with either metformin or Pioglitazone, CAS# 112529-15-4, patients experienced significant improvements in their glycemic control, as compared to monotherapies.  In the same class of drugs as Januvia, which generated sales of roughly $3.3 billion in 2011, alogliptin is slated to succeed. In fact, three formulation of alogliptin were approved in late January 2013 by the FDA:  Nesina, which are fixed dose alogliptin tablets; Oseni, which combine both alogliptin and pioglitazone; and the aforementioned Kazano, which is the alogliptin and metformin hydrochloride tablet. The FDA approved these three formulations of alogliptin, to be taken alongside a dietary and exercise program to control type 2 diabetes. These approvals are based on data from separate studies for all 3 formulations.  There were 14 clinical trials of alogliptin as a monotherapy, which involved 8,500 patients with type 2 diabetes. Results from these 14 trials were noteworthy, producing hemoglobin A1C reductions of 0.4 to 0.6 percentage points at 26 weeks when compared with a placebo. The alogliptin and pioglitazone combination was involved in 4 clinical trials, which included a little over 1,500 patients. Results from these studies indicated additional A1C reductions of 0.4 to 0.6 percentage points over pioglitazone monotherapy, and 0.4 to 0.9 percentage points over alogliptin alone.  Dosages of these 3 formulations of alogliptin, all developed and marketed by Takeda are: Nesina (alogliptin) 6.25 mg, 12.5 mg, and 25 mg Tablets; Kazano (alogliptin and metformin HCl) 12.5 mg/500 mg and 12.5 mg/1000 mg Tablets; and Oseni (alogliptin and pioglitazone) 25 mg/15 mg, 25 mg/30 mg, 25 mg/45 mg, 12.5 mg/15 mg, 12.5 mg/30 mg, and 12.5 mg/45 mg tablets.

LGM Pharma provides alogliptin for research and development purposes, and offers clients continued support throughout the R&D process. Type 2 diabetes is the most common form of diabetes affecting patients globally, and the United States alone has over 23 million people suffering from this condition. Continued research and development of new and innovative treatments to combat this ever growing patient population is not only prudent, but also extremely necessary.

Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e)+A13(1). Any patent infringement and resulting liability is solely at buyer risk.