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

FDA Announces Approval of Gileads Once-A-Day Pill Sofosbuvir

Sofosbuvir 1190307-88-0 FDA ApprovalOn December 6th, 2013 the FDA announced the approval of Gilead’s once-a-day pill Sofosbuvir, marketed as Sovaldi. The approval comes shortly after an FDA advisory committee awarded Gilead breakthrough therapy status for the once-a-day pill Sofosbuvir at the end of October 2013 (see previous Sofosbuvir article). The FDA committee also unanimously recommended the approval of Sofosbuvir in conjunction with Ribavirin and Pegylated Interferon for treatment naïve patients with chronic hepatitis C who have the specific genotype 1 and genotype 4 infections.

The once-a-day pill Sofosbuvir is designed to treat the main forms of hepatitis C that affect U.S. patients. This highly anticipated approval comes as the FDA recommends people born between 1945 and 1965 get tested for hepatitis C. Baby boomers are five times more at risk to have the disease than other age groups – even more so than younger people who share needles or have unprotected sex with hepatitis C infected individuals.

Sofosbuvir is the first in a new class of nucleotide polymerase inhibitors that doesn’t require interferon injections. This once-a-day pill pushes the cure rate much higher than before.

As a nucleotide analogue, Sofosbuvir has demonstrated safe and formidable effects in four Phase 3 trials coined FISSION, FUSION, NEUTRINO and POSITRON. The POSITRON study specifically showcased the benefits of Sofosbuvir in patients who were unable or unwilling to take adjunctive interferon. Patients with genotypes 1 and 4 hepatitis C infections will still need to be treated with peg interferon, but the concomitant use of Sofosbuvir makes a shorter treatment time available, specifically 12 weeks duration, creating a lesser probability of adverse effects. Patients with the hepatitis genotype 3 infections displayed success in the FUSION trial after a full 16 weeks of treatment with Sofosbuvir. While a 12 week course of treatment did reveal positive data, the percentage of genotype 3 patients finding relief grew substantially with the extended course of treatment.

Gilead has announced that it would sell the Sovaldi 12-week treatment for $84,000. Patients with a less common form of hepatitis C might require a 24 week treatment of the drug, upping the cost to $168,000. Existing hepatitis C drugs on the market average between $25,000 and $50,000 per treatment.

Next year Gilead plans on filing for FDA approval of a combination pill containing Sofosbuvir and Ledipasvir, another antiviral drug, that could become the first all-oral regimen for the most common form of hepatitis C, long viewed as the holy grail of treatments by drug makers. Similar development efforts are underway from competitors like Abbott Laboratories, Bristol-Myers Squibb Co., Vertex Pharmaceuticals and others.

LGM Pharma provides the Sofosbuvir CAS# 1190307-88-0 API 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.

FDA Grants Sofosbuvir Breakthrough Therapy Designation

Sofosbuvir 1190307-88-0 Breakthrough Therapy StatusThe end of October 2013 saw a nod from the FDA given to Gilead’s New Drug Application for Sofosbuvir. As a greatly needed treatment for hepatitis C Sofosbuvir has proven to be effectual and tolerable in a number of studies. Sofosbuvir is marketed by Gilead Science, Inc. and is clearly set up for success in the pharmaceutical arena. With roughly 170 million cases of hepatitis C around the world, the Sofosbuvir breakthrough therapy designation is crucial to fulfill the need for novel and effective treatments. The expanding patient population in the United States infected with chronic cases of hepatitis C hovers around 4 million people. Additionally, there are a substantial number of new patients diagnosed with hepatitis C each year in the U.S., with almost 30,000 new American diagnoses each year. The Advisory Committee of the FDA clearly supported Gilead’s Sofosbuvir with a unanimous vote of support, granting Sofosbuvir breakthrough therapy designation status. The FDA committee also unanimously recommended the approval of Sofosbuvir in conjunction with Ribavirin and Pegylated Interferon for treatment naïve patients with chronic hepatitis C who have the specific genotype 1 and genotype 4 infections.

As a nucleotide analogue, Sofosbuvir is designed as a once daily treatment which has demonstrated safe and formidable effects fighting the hepatitis C virus. Studies included four Phase 3 trials coined FISSION, FUSION, NEUTRINO and POSITRON. The POSITRON study specifically showcased the benefits of Sofosbuvir in patients who were unable or unwilling to take adjunctive interferon. Patients with genotypes 1 and 4 hepatitis C infections will still need to be treated with peg interferon, but the concomitant use of Sofosbuvir makes a shorter treatment time available, specifically 12 weeks duration, creating a lesser probability of adverse effects. Patients with the hepatitis genotype 3 infections displayed success in the FUSION trial after a full 16 weeks of treatment with Sofosbuvir. While a 12 week course of treatment did reveal positive data, the percentage of genotype 3 patients finding relief grew substantially with the extended course of treatment.

The FDA is looking at a possible approval of Sofosbuvir in early December 2013. LGM Pharma provides the Sofosbuvir CAS# 1190307-88-0 API 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.

Exercise is Possible for Patients Suffering from PAH with Ambrisentan

AmbrisentanPatients suffering from debilitating pulmonary arterial hypertension, or PAH, find extensive relief when treated with ambrisentan. Also known as the brand name Letairis, marketed by Gilead, ambrisentan is effectual at preventing the thickening of the blood vessels, particularly those in the heart and lungs. Ambrisentan, CAS number 177036-94-1,  treats the high blood pressure in the arteries of the patient’s lungs, lowers their blood pressure and helps the heart to pump better and more efficiently.

Ambrisentan is available in oral tablets, both 5 and 10 milligrams. Typically taken orally with or without food, the initial dose for the majority of patients is 5 milligrams once a day. The dose may be increased if needed on a case by case basis to 10 milligrams once a day. Side effects may include vomiting, headache, constipation, stomach pain, sinus pain and sore throat. Due to the risk of serious birth defects, Letairis is currently only offered to patients through a program called LEAP, or Letairis Education and Access Program, in the United States. This is not the standard worldwide. As Letairis approaches the end of it’s patent December 30, 2014, researchers are seeking to develop generic formulations of this unique product to provide greater options for patients.

One of the distinct benefits of ambrisentan is how effective it is at improving the ability of patients to exercise, and also preventing the PAH condition from getting worse. The patient population suffering from untreated pulmonary arterial hypertension experiences symptoms such as shortness of breath, especially when exercising, exhaustion, fainting, dizziness and swelling of the extremities, specifically the legs and arms. Ambrisentan aids patients by blocking the effects of a substance called endothelin, a small peptide hormone which is made by the body in greater then normal amounts in patients with PAH. This excess endothelin causes the blood vessels to constrict and leads to an overgrowth of the muscle in the walls of the blood vessels in the lungs. Efficacious at blocking the action of endothelin, ambrisentan is a boost for the health and activity of people in this patient group. There have been gratuitous amounts of studies completed regarding ambrisentan, primarily sponsored by Gilead, which indicated significant benefits to patients who received the drug. These aforementioned studies were mainly short term, and randomized, however there were also several long term open label trials as well. Data recorded from both short and long term trials demonstrated clearly that ambrisentan improves exercise capacity and delays clinical worsening in PAH patients. Other benefits to the administration of ambrisentan include a low incidence of liver toxicity, a lowered incidence of interactions with other drugs, including anticoagulants, and a potent bioavailability which allows even low doses for a therapeutic effect. LGM Pharma is a provider of the API ambrisentan for research and development purposes.

 

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.

Adefovir Dipivoxil Effective Treatment for Patients with Chronic Hepatitis B

Adefovir DipivoxilAdefovir dipivoxil, CAS number 142340-99-6, is a nucleotide analog reverse transcriptase inhibitor, or “ntRTI”. Previously called bis-POM PMEA, adefovir dipivoxil is used is the treatment of chronic hepatitis B. Also produced under the trade names Hepsera and Preveon, adefovir dipivoxil is approved by the FDA for treatment in patients with active cases of chronic hepatitis B.  Adefovir dipivoxil acts as a blocker to the enzyme reverse transcriptase, thus inhibiting the ability of this enzyme to reproduce in affected patients. LGM Pharma is a provider of adefovir dipivoxil for research and development purposes, and provides support for clients throughout the research and development process.

Irving Millman

Photo courtesy of Fox Chase Cancer Center
Irving Millman, a microbiologist whose work led to the creation of a vaccine against hepatitis B that is credited with saving millions of lives, died on April 17, 2012 in Washington. He was 88.

Adefovir dipivoxil has proven it’s efficacy, as well as safety, in clinical studies. In a Phase 2 trial, adefovir dipivoxil proved to be a strong competitor when tested against lamivudine-resistant strains of the hepatitis B virus. The aforementioned trial randomly chose 515 patients with chronic hepatitis B, and also positive for the hepatitis B e antigen. These patients were given an oral tablet of 10 milligrams, 30 milligrams or a placebo of adefovir dipivoxil. After 48 weeks of testing, patients who received either the 10 or 30 milligram dose showed an increase of the HBeAG antibodies. Patients also displayed reduced serum HBV DNA and alanine aminotransferase levels, as well as improved liver function.

The trade name of adefovir dipivoxil, Hepsera (or Preveon), made by Gilead, was the first nucleotide analog to be approved for the indication of chronic and active hepatitis B in patients. Additional research in phase 3 trials of Hepsera indicated improvement in liver function for 64% of patients studied, as compared to 33% of patients who received a placebo. While these are all positive results, there have been side effects noted. Notable negative effects of adefovir dipivoxil include weakness, headache, nausea, abdominal pain, diarrhea and dyspepsia. Severe side effects are not common, but possible. These include lactic acidosis and nephrotoxicity.

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.