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

Paliperidone Approved as Quarterly Therapy for Patients with Schizophrenia

Paliperidone Palmitate Approved as Quarterly Therapy for Patients with SchizophreniaThe FDA gave the green light in late May 2015 with their approval of a quarterly dosing schedule of Paliperidone Palmitate, also known as Invega Trinza. Marketed by Janssen Pharmaceuticals this novel dosing regimen is the first ever quarterly dosing therapy for patients with Schizophrenia. Paliperidone is dispensed to patients via an intramuscular injection every three months, offering patients freedom from daily medications. This novel administration not only helps to insure patient’s medication adherence, but it also takes the stress of remembering daily, weekly and monthly medications away. The only prerequisite for patients seeking to take this medication is an adequate, once a month therapy with Invega Sustenna for at least four months prior to beginning Invega Trinza (Paliperidone).

A comprehensive phase III maintenance trial determined the efficacy and safety of the Paliperidone three-month formula, comparing it with a placebo in regard to delaying the time gleaned before a relapse of schizophrenic symptoms returned. This randomized study included a three-week screening phase; a lengthy seventeen-week flexible dosing phase; an open-label transition phase; a double-blind phase which was open ended and a twelve-week open-label maintenance phase. Approximately 305 patients between the ages of 19 and 70 years of age participated in this successful study. The patients were assigned at random to receive either three months of Paliperidone Palmitate or a placebo, via injection. The group of patients who were administered the Paliperidone showed a distinct advantage in terms of time until a relapse of symptoms, as compared to the patients who received the placebo. A staggering 93 percent of patients who were dosed with Paliperidone (Invega Trinza) did not experience a significant return of schizophrenia symptoms while on the three-month dosage. There were some reports of minor side effects, such as akathisia, headache and slight weight gain.

As a chronic and very severe brain disorder Schizophrenia occurs in about one percent of the U.S. population. More than 21 million people around the globe suffer from Schizophrenia. Manifestation of Schizophrenia and the first “episode” is usually around 21 years of age for males and about 27 years of age for females. Men far outnumber the patient population with a Schizophrenia diagnosis by age 30. The good news is that this potentially debilitating condition is treatable with accurate diagnosis and proper medication and care.

LGM Pharma can assist clients as a supplier/distributor of the API Paliperidone, CAS #144598-75-4 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.

Sonidegib FDA Approved as Once Daily Treatment for Locally Advanced Basal Cell Carcinoma

Sonidegib FDA Approved for Locally Advanced Basal Cell CarcinomaOn July 24, 2015 the FDA approved Sonidegib, marketed by Novartis AG as the once daily pill Odomzoa for the treatment of locally advanced basal cell carcinoma. Specifically for patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or who are not candidates for surgery or radiation therapy.

Sonidegib, also known as the compound LDE225, had recently captured the attention of the pharmaceutical and medical industry worldwide, due to extremely successful study data. Conducted by Novartis, the reports from a Phase 2 study have shown Sonidegib to be a top-notch drug, eradicating basal cell carcinoma in a number of patients. Dispensed as an oral treatment for patients suffering from advanced basal cell carcinoma, the study results easily met the primary endpoint, garnishing an objective response rate within six months’ time. The objective response was based on the criteria of the complete absence of advanced basal cell carcinoma, and clinically sizable tumor shrinkage. The pharmaceutical industry was poised for an earlier than planned FDA application from Novartis, based on these incredible Phase 2 results.

smoothendAs an effectual drug that inhibits a receptor coined smoothened, that regulates the hedgehog signaling pathway, Sonidegib efficiently and safely blocks tumor growth. With basal cell carcinoma accounting for over 80 percent of non-melanoma cancers, treatments for advanced stages of this form of skin cancer are urgently needed. The advent of an easy to dispense oral treatment to fight this now common cancer worldwide offers hope for a greater number of patients. Around the world there is a 10 percent incident increase of basal cell carcinoma every year, which is likely due to an aging population and greater exposure to dangerous ultraviolet rays. Basal Cell Carcinoma does not often metastasize, but more advanced cases of this regularly seen disease are manifesting. The exciting data gleaned from Novartis’s study of Sonidegib showcasing patients who achieved complete remission is nothing short of miraculous.

LGM Pharma provides Sonidegib CAS# 956697-53-3, 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.

CF Therapy Combination Lumacaftor and Ivacaftor Approved

Cystic Fibrosis Therapy Combination Lumacaftor and Ivacaftor ApprovedOn July 2, 2015 the FDA announced its approval for the potent duo of Lumacaftor and Ivacaftor to treat patients suffering from Cystic Fibrosis (CF). Coined Orkambi, which is marketed by Vertex Pharmaceuticals, this effectual treatment is specifically approved for patients ages 12 and older who have the homozygous F508 mutation of the CF transmembrane conductance regulator, or CFTR gene. Orkambi has also already attained breakthrough therapy and Orphan Drug status in the United States and it is currently awaiting an EMA review. While both Lumacaftor and Ivacaftor have not proven to be efficacious for patients with CF as monotherapy, a Phase 2 study of the combination proved these two drugs greatly improve clinical outcomes in patients who are homozygous for the Phe508del CFTR mutation.

Two successful Phase 3 studies led the FDA to their positive opinion of Lumacaftor and Ivacaftor. Coined TRAFFIC and TRANSPORT these trials were comprehensive and multinational. As double-blind, placebo-controlled, randomized and parallel-group studies, both Lumacaftor and Ivacaftor proved to be effectual, tolerable and safe. The studies were designed to evaluate primarily the efficacy of Lumacaftor and Ivacaftor in combination for patients with the homozygous Phe508del CFTR mutation form of CF. Safety was a secondary objective of the study. The patients in these studies were assigned to one of three random groups and given one of the following doses:

  • 600 milligrams of Lumacaftor once a day in combination with 250 milligrams of Ivacaftor every 12 hours for 24 weeks.
  • 400 milligrams of Lumacaftor every 12 hours in combination with 250 milligrams of Ivacaftor every 12 hours for 24 weeks.
  • A Lumacaftor-matched placebo every 12 hours in combination with an Ivacaftor-matched placebo every 12 hours for 24 weeks.

There were a total of 1,122 patients who underwent randomization, specifically 559 in the TRAFFIC study and 563 in the TRANSPORT study. At least one dose of the study drug or the placebo drug was dispensed to 1,108 patients. Both studies of the Lumacaftor/Ivacaftor combination elicited viable clinical changes as early as 15 days into the studies, and showed a sustained efficacy through the 24 week mark. In both studies the percentage of patients who had a relative improvement in the percentage of predicted FEV1 of 5% or higher was demonstrative in the patients who received Lumacaftor and Ivacaftor, as compared to the patients who received the placebo. Additionally, clinically significant reductions of protocol-defined pulmonary exacerbations were found in the patients who were dosed in both Lumacaftor–Ivacaftor trial groups. The reporting of adverse events was similar in both the Lumacaftor/Ivacaftor and placebo groups, with common complaints being a higher than normal creatine kinase level, rash and bronchospasms.

Cystic Fibrosis ManifestationsAs a genetic disease associated with high rates of early-onset mortality Cystic Fibrosis affects roughly 30,000 patients in the United States. Of these patients almost 30 percent are homozygous for the F508 mutation. The recent approval of Lumacaftor and Ivacaftor as Orkambi is an encouraging development which is greatly needed for this patient population.

LGM Pharma can assist clients as a supplier/distributor of the Lumacaftor CAS# 936727-05-8 API and the Ivacaftor CAS# 873054-44-5 API 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.

Sacubitril and Valsartan Combo Entresto is FDA Approved

Entresto LCZ696 (Valsartan/sacubitril)  FDA approved July 7, 2015Entresto, the novel combination therapy which combines Sacubitril and Valsartan, was FDA approved on July 7, 2015. Previously known as the investigational compound LCZ696, Entresto received an FDA nod to reduce the risk of both hospitalization and cardiovascular mortality in patients with chronic heart failure, especially those with a reduced ejection fraction and an NYHA Class II-IV diagnosis.

Perhaps the biggest news-maker from this FDA nod is the novel molecule Sacubitril, getting it’s first FDA approval. Sacubitril is an effectual first-in-class neprilysin inhibitor. Combined with the angiotensin receptor antagonist Valsartan, Entresto shined in comprehensive studies.

The FDA decided to quickly approve Entresto, which is marketed by Novartis, after receiving results from a vast study coined PARADIGM-HF. This study has proven to be the largest clinical trial ever conducted in patients with heart failure to date. The FDA’s decision is based on results from the 8,442-patient who were enrolled in this trial, which proved Entresto was both clinically and statistically superior to Enalapril, a standard ACE inhibitor used for heart failure therapy. Entresto drove the risk of cardiac mortality and hospitalization from heart failure down by 20 percent in the trial, meeting the primary study endpoint. Adverse effects from Entresto were not deemed severe, and included dizziness, cough, and lowered blood pressure, as well as higher than normal potassium levels, which could affect patients with preexisting kidney disease.

A staggering six million people in the United States are suffering from heart failure, with nearly half of these patients also exhibiting the reduced ejection fraction form of this disease. Patients diagnosed with chronic heart failure endure repeated hospital visits, fluid retention, breathlessness, extreme fatigue and face a high risk of mortality. The ageing population both in the U.S. and worldwide will undoubtedly lead to more cases of heart failure being diagnosed, and experts predict a hefty eight million Americans will be diagnosed with heart failure by 2030.

Entresto has been approved in three dosage strengths: 24/26 milligrams, 49/51 milligrams, and 97/103 milligrams of Sacubitril/Valsartan, respectively. The NEJM has referred to these dosages as 50 milligrams, 100 milligrams, and 200 milligrams for clinical trial literature purposes regarding the PARADIGM-HF results. The optimal dose for patients with heart failure who have a reduced ejection fraction and are classified as having a NYHA Class II-IV diagnosis is 97/103 milligrams of Entresto twice a day by mouth.

LGM Pharma can assist clients as a supplier/distributor of the API Entresto LCZ696 (Valsartan/sacubitril) CAS# 936623-90-4 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.