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

New Trametinib and Palbociclib Combo Drug for Melanoma Being Studied

Pfizer and GlaxoSmithKline Combat Melanoma

New Trametinib and Palbociclib Combo Drug for Melanoma Being Studied

An announcement was made by pharmaceutical giants Pfizer and GlaxoSmithKline at the end of November 2013 regarding their agreement to combine efforts in researching a novel melanoma treatment. The clinical study the two companies have commenced involves adult patients with unresectable, metastatic melanoma. This partnership will be a Phase I/II trial designed to determine the effects of Pfizer’s investigational treatment, Palbociclib when added to GlaxoSmithKline’s Trametinib. The MEK inhibitor Trametinib is currently on the market as the brand name Mekinist, as it was approved in early 2013 for the treatment of advanced melanoma.  As an oral inhibitor of both CDK 4 and CDK 6, Palbociclib has already been granted breakthrough status by the FDA in April of 2013, as a treatment for metastatic breast cancer. Both pharmaceutical companies are eager to evaluate the potential anticancer therapy that the combination of these two formidable products renders.

The combination study evaluating Trametinib and Palbociclib is open-label and seeking to determine the best recommended combination regimen of both drugs. As a dose escalation study, this trial of Trametinib and Palbociclib will also evaluate the effects of this dynamic duo of melanoma drugs regarding safety, tumor biomarkers and anti-cancer activity in specific patient populations. These specific groups of patients with metastatic melanoma include people with the BRAF V600 wild type melanoma, as well as those patients with NRAS mutations.

A startling 1 in 50 Americans has a lifetime risk of developing melanoma. Young adult women have experienced a surge in cases-over 50 percent since 1980. Additionally, the American Cancer Society estimates that roughly 77,000 Americans will be diagnosed with melanoma this year, and 9,500 of these patients will not survive. Research and development of medications to treat this growing patient population is necessary and urgent. LGM Pharma provides the APIs Trametinib CAS# 871700-17-3 and Palbociclib CAS# 571190-30-2 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.

Eplerenone for Acute ST-Segment Elevation Myocardial Infarction

EplerenoneExciting results were revealed in Mid-March of 2013 when the REMINDER trial touted the success of Eplerenone for treating acute ST-Segment Elevation Myocardial Infarction, also known as STEMI. The results from this study were presented at the 62nd Annual Scientific Session of the American College of Cardiology, by Pfizer, who markets Inspra which is the brand name of Eplerenone. The patent for Inspra expires for Pfizer on December 8, 2019. This double-blind and randomized trial included 1,012 patients who had an acute ST-segment elevation myocardial infarction, or STEMI. The patients in the study received between 25 and 50 milligrams of Eplerenone or a placebo, alongside optimal standard therapy. The patients who were dosed within the first 24 hours of symptom onset, especially those participants dosed within the first 12 hours of symptom onset, had a significant reduction in both heart failure and mortality as compared to the placebo group.

As a steroid nucleus-based mineralcorticoid receptor antagonist, Eplerenone is currently indicated in the United States to treat left ventricular systolic dysfunction, certain types of congestive heart failure and specific cases of hypertension. The European Union has also approved Eplerenone, along with best standard therapy, to reduce the risk of death from cardiovascular events in patients with NYHA class II heart failure. Japan has approved Eplerenone for the treatment of acute hypertension only. Patients who have known or prior cases of hyperkalemia should not be administered Eplerenone.  People who have type 2 diabetes and microalbuminuria must be monitored if dosed with Eplerenone due to a heightened risk of renal insufficiency. Side effects reported by patients include dizziness, fatigue and mild diarrhea.

LGM Pharma provides Eplerenone 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.

Zmax is Azithromycin to the Max

InfluenzaThe patent for the omnipotent Zmax is set to expire for Pfizer on May 30, 2017. This is extremely relevant for research and development as a generic formulation of this cogent drug, specifically azithromycin, can now be produced. Azithromycin is indicated for mild to moderate infections including acute bacterial sinusitis in adults due to haemophilus influenzae, moraxella catarrhalis or streptococcus pneumonia; community-acquired pneumonia in adults and pediatric patients who are six months of age or older due to chlamydophila pneumonia; haemophilus influenza; mycoplasma pneumoniae and streptococcus pneumonia. LGM Pharma provides API Azithromycin cas number 83905-01-5, as well as the TEVA API Azithromycin for research and development.

With a unique one time dose of 2 grams, for all adult patients regardless of weight, this easy dose is simple and singular in nature. Pediatric patients six months of age and older are typically dosed a single dose of 60 mg/kg (equivalent to 27 mg/lb) body weight. The idea of one dose of antibiotic which provides complete therapy is appealing to patients and practitioners alike. Dr. Joseph Feczko, chief medical officer at Pfizer, states, “A single, high-dose antibiotic is an important advance in treating certain types of sinusitis and pneumonia in adults.” He also adds, “Results showed that one dose of Zmax was as effective as currently available treatments that must be taken for seven to ten days.” Side effects are mild, and may include diarrhea, nausea, abdominal pain and headache.

AzithromycinAzithromycin (Zmax) must be administered as a single dose of approximately 2 grams, at least one hour before or two hours after eating a meal. In the first 24 hours after a dose of azithromycin/Zmax the amount of drug that gets into the tissue is three times higher than a standard dose of immediate-release azithromycin. The immediate-release azithromycin is recognized as the brand name Zithromax, and it is effective by “front loading” or providing high drug levels earlier in the course of infection when the bacterial burden is believed to be highest. The innovation in the azithromycin/Zmax formulation is the microsphere technology which allows for the release of this medication in the small intestine, rather than in the stomach, lending to a more favorable side-effect profile. Additionally, the long half-life and high tissue penetration makes it conceivable for this form of azithromycin to deliver an entire course of therapy as a single dose.

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.

 

 

Migraine Sufferers Find Relief with Eletriptan Hydrobromide

MigraineEletriptan Hydrobromide, CAS number 143322-58-1, is a medication indicated for the acute treatment of migraine with or without aura in adults. Known as Relpax, which is marketed by Pfizer, the patent expiration for Eletriptan Hydrobromide is on December 26, 2016 (Patent Use Code U – 876 – TREATMENT OF MIGRAINE WITH OR WITHOUT AURA). Available in 20 milligram and 40 milligram tablets, eletriptan hydrobromide has been shown to be more effectual with the higher dosage of 40 milligrams. Doses of 80 milligrams in trials were deemed efficacious, but led to a greater instance of adverse effects. The maximum recommended dose of eletriptan hydrobromide is 40 milligrams. Common side effects of eletriptan hydrobromide are dizziness, nausea, weakness, drowsiness, and pain or pressure sensations in the chest or throat.

eletriptan hydrobromide CAS No: 177834-92-3The efficacy of eletriptan hydrobromide, or Relpax, for the acute treatment of migraines was evaluated in eight double-blind, placebo-controlled and randomized studies. All eight studies used 40 milligrams as a dosage amount, and seven studies evaluated an 80 milligram dose as well. In addition, two of the eight studies included a 20 milligram dose. These outpatient studies included adults, with only one study involving adolescents ages 11 to 17. The patients in the seven adult studies were mostly female, specifically 85 percent of patients. Caucasian patients were also the majority in these studies, with 94 percent of the patients being of this race. The mean age of patients was 40 years of age, although the patient age range was from age 18 to age 78. All of the patients in these studies were told to treat their headache if it was moderate or severe in nature. Some patients also experienced symptoms alongside their migraines, such as nausea, vomiting, photophobia and phonophobia. Patients were assessed two hours after their dosage of eletriptan hydrobromide, and up to 24 hours after their dose. Results from the seven adult studies revealed that the percentage of patients who achieved a headache response 2 hours after treatment with eletriptan hydrobromide was significantly greater when compared to patients who received a placebo. The study involving adolescents also indicated a positive response rate for patients who were dosed with eletriptan hydrobromide.

There are more than 37 million Americans who suffer from migraines. Approximately 3.2 million Americans have chronic migraine, which is defined as migraine or tension-type headaches 15 or more days a month. According to the World Health Organization, migraines are responsible for at least 1 percent of the total U.S. medical disability burden. These statistics are serious, and indicate an urgent need for research and development of medications to treat this disabling condition. LGM Pharma provides API Eletriptan Hydrobromide for research and development purposes. Clients can be assured of complete support from LGM Pharma 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.