Drugs In The Pipeline For 2013 And Beyond
In 2011, when the world's best-selling drug went off patent, the era of Pfizer's Lipitor began to close. Lipitor was just one of a number of blockbuster drugs losing patent protection this year and last, to wit: Eli Lilly's antipsychotic Zyprexa, Johnson and Johnson's antibiotic Levaquin and ADHD medicine Concerta, AstraZeneca's antipsychotic Seroquel, Merck's asthma drug Singular, and Takeda's diabetes drug Actos.
The coincidence of so many top-selling meds losing patent protection within such a short time frame led to the term 'the patent cliff.' The metaphor captures some of the panic drug companies feel as they lose their exclusive grip on blockbuster medications. So what's a poor pharmaceutical company to do when faced with losses in the millions if not billions?
Of course the first option for drug companies is to somehow stave off patent expiration. There are a variety of strategies for this, leading some, with a rather cynical take, to call it 'evergreening.'
But even testing the drug on children (an automatic 6-month patient extension) won't stave off the inevitable forever.
'The pipeline' refers to a biotechnology company's research and development progress and, for pharmaceutical companies, treatments that are already in clinical trials awaiting FDA approval. What's in the pipeline helps establish a company's investment potential, so it's important that there's a lot cooking in there--and that there's good press about what's coming through, as well.
Pfizer gets a lot of coverage in the financial papers--even if some of it turns out to be misguided.
For example, Pfizer got the media coverage all drug companies desire on May 4 from Seeking Alpha, a stock market blog that provides free stock market analysis. A piece entitled "Pfizer: Alzheimer's Drugs Will Carry Stock To New Highs In 2013” had a subheading "strong pipeline."
Turns out that was too optimistic, as Pfizer's Alzheimer’s drug--along with Johnson and Johnson's--both failed to produce. But many stock analysts still hold hope that Pfizer has a new 'cash cow’ coming down the pipeline.
Daily Finance notes that Pfizer currently has 87 drugs in its pipeline. While its true that most are in the early stages, 11 are ready to be reviewed by the FDA.
That number puts it ahead of most of its rivals, with Eli Lilly, a close second, having 63 drugs in Phases 1-3, plus one currently being reviewed. Bristol-Myers Squibb has 46 drugs in development, 7 under review, Merck has 35 drugs in Phase 2 or 3 with two under review, and Johnson and Johnson has 18 drugs that are already in Phase 3 clinical trials or up for FDA approval.
But, of course, as the journal points out, "Quality trumps quantity. . . . One or two blockbusters can be better than several lower-revenue drugs."
So what does Pfizer have up its sleeve that might begin to fill the very big shoes of Lipitor?
Well, the company has diversified the therapeutic areas under research, with 26% of R&D efforts going toward oncology treatments, 20% to neuroscience and pain, 17% to cardiovascular and metabolic diseases, 14% to inflammation and immunology, 5% to vaccines, and 18% toward 'other.'
Pfizer has several medicines for diabetes alone coming up, in Phase I and Phase II trials, almost all meant to treat type 2 diabetes.
But, notes Seeking Alpha, its blockbuster potential in this area is limited by the existing treatments of Merck and Sanofi. 10% of Sanofi's total sales come from Lantus, a diabetes drug useful for both types 1 and 2, and Merck made $1.3 billion off its Januvia franchise in the first quarter of this year alone.
So hopes are pinned on Pfizer's tofacitinib, currently under FDA review, as the treatment with the potential to earn $1 billion or more in sales, easing the gaping wound left by Lipitor. Tofacitinib prompts such high hopes because it might possibly treat rheumatoid arthritis, psoriasis, and irritable bowel syndrome. Some analysts have pinned this as the cash cow Pfizer so badly needs to replace treatments lost to the patent cliff.
If it gets approved, Tofacitinib would be first treatment for rheumatoid arthritis (RA) in a new class of medicines (known as Jenus kinase, or JAK, inhibitors), and the first JAK inhibitor approved for rheumatoid arthritis.
Tofacitinib showed statistically significant improvement compared to placebo in decreasing the symptoms of RA (as measured by 20% improvement in the American College of Rheumatology scale), in improving physical function (as measured by mean change in Health Assessment Questionnaire-Disability Index), and in leading to remission (as measured by Disease Activity Score 28 ESR).
Joel Kremer, MD, chief of medicine at Albany Medical College in N.Y., after analyzing the data, commented, "Tofacitinib appears to reduce the signs and symptoms of rheumatoid arthritis very quickly. We hope that after carefully considering the benefit/risk equation, this compound will provide an additional valuable treatment option for patients who have experienced inadequate response to prior treatments."
Pfizer also believes its blood thinner Eliquis, which it is developing with Bristol-Myers Squibb (see below) could be a big money-maker.
BMS held the patent on blood-thinner Plavix, one of the top 10 best-selling drugs of all time. In fact, in 2010 Plavix earned BMS and its co-marketer Sanofi-Aventis more than $6.1 billion in U.S. sales alone.
Plavix lost patent protection in May and went from almost 35% of BMS's sales to 25% in the last quarter alone--and further declines are sure to follow.
So BMS and Pfizer are holding out hope that blood thinner Eliquis (apixaban) could be a blockbuster. One analyst believes the potential market for the drug is $2.5 billion a year.
Initial responses to the clinical trials were effusive in their praise. One heart blog wrote, "In cardiology, apixaban may be the golden mean of anticoagulation, achieving the ideal balance of reduced strokes and deaths without causing any additional bleeding complications."
The Phase III clinical trials were large in scope, comparing Coumadin (warfarin), the most widely used blood-thinner today, with Eliquis. Hopes were that the treatment would not be too inferior to Coumadin--but researchers were overjoyed when the drug was not just not inferior, but actually superior in efficacy.
The drug trials found that Eliquis yielded a significant reduction in mortality, and reduced the risk of bleeding.
SeekingAlpha claims that by 2015 the drug could be worth nearly $3.5 billion, which would, indeed, make it the blockbuster BMS needs.
Eli Lilly has been hit hard by that patent cliff. Antipsychotic Zyprexa (olanzapine), which once earned $5 billion a year, came off patent in 2011, and its revenue plummeted. Its next largest drug is antidepressant Cymbalta, due to lose patent protection at the end of 2013. Humalog, its 4th largest drug, is also due to come off patent in late 2013.
Clearly, Lilly needs a strong future. Of Eli Lilly’s 63 drugs in the pipeline, 27 are in Phase I, 23 in Phase II, 12 in Phase III, and one, Liprotamase, for cystic fibrosis, is under regulatory review.
Biologically engineered Liprotamase is really a pancreatic enzyme replacement drug, which will also help those with pancreatitis and those who've had a pancreatectomy. It was acquired when Lilly purchased Alnara Pharmaceuticals Inc for $380 million, and was one of the main drugs in Alnara's pipeline at the time.
The FDA rejected approval of the drug initially, claiming its risks outweighed its benefits, and that it didn't increase fat absorption as much as similar treatments. The FDA requested an additional clinical trial.
But Lilly was undeterred, believing it has a strong chance at making a go with Liprotamase.
Eiry Roberts, a Lilly vice president, said in the statement, “Lilly is looking forward to further discussion with the FDA to address the items outlined in the letter and provide the requested information as quickly as possible."
The drug is meant to complete with Abbott Laboratories' Creon, Johnson & Johnson's Pancreaze, and Eurand NV’s (based in Amsterdam) Zenpep.
Two particularly hopeful treatments in terms of revenue potential farther down the pipeline are dulaglatuide, a once-weekly treatment for diabetes in Phase clinical 3 trials and Ixekizumab a treatment for psoriasis, which is in Phase II trials.
Dulaglatuide works by stimulating cells to release insulin only when blood sugar levels are high.
Gwen Krivi, Ph.D., vice president, product development, Lilly Diabetes, said of the drug, “We believe dulaglutide, if approved, can bring significant benefits to people with type 2 diabetes.”
In fact, it might help to control both diabetics' blood sugar and their high blood pressure.
Eli Lilly CEO John Lechleiter believes the drug has the potential to be a blockbuster. Lilly could be ready to seek approval by 2013.
Dulaglatuide isn't the only diabetes drug in Lilly's pipeline. The as-yet-unnamed insulin-like treatment, LY2963016, if approved, could be competition for Sanofi's diabetes treatment Lantus. EvaluatePharma writes of the drug, "The long-acting anti-diabetic is the [company's]. . . most valuable R&D product, and given its biological similarity to Sanofi’s Lantus success will be expected."
There's a way to go, though. The molecule is now being tested both in type 1 and type 2 diabetics. The studies include 600 type 2 subjects and 400 type 1 patients, comparing the treatment with Lantus. Lilly is hoping for results--and good ones--by year's end or by 2013.
Aside from diabetes care, Eli Lilly has another drug for which it has high hopes. Ixekizumab, an injection, treats psoriasis, a skin disease with itchy, red, scaly patches. The disease is one of the most common skin conditions in the world, affecting approximately 7.5 million people in the U.S. alone.
In a study of 142 patients, significantly more patients achieved improvement in their psoriasis than with placebo. 40% had their psoriasis plaques completely clear up. Notably, researchers found no serious adverse effects with the drug.
In Phase III studies, ixekizumab is also currently being evaluated for other indications, like psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis, a type of arthritis of the spine.
According to Seeking Alpha, Merck has "fantastic pipeline of new drugs, which should soon add demonstrably to its sales."
Merck is currently filing New Drug Applications or providing more data to the FDA for at least 4 treatments the company believes it can get approved before the end of 2013. They include Atozet, an investigational medicine for high cholesterol, Bridion, an anesthesia-related drug already approved in the European Union, Vintafolide, a form of targeted chemotherapy, and Suvrexant.
Suvrexant, for insomnia, together with the heart drugs Tredaptive, Vorapaxar, and anacetrapib [see “Merck is 'all heart' over the next few years"] due out in the next few years holds great promise for Merck. The sleeping drug has a potential $2 billion market (18 million U.S. patients.
In 2013 Merck is expected to submit AIT Ragweed (allergy), AIT grass (allergy), both Tredaptive and Vorapaxar, and Odanacatib, to treat osteoporosis, which affects approximately 200 million women.
FierceBiotech writes that "Suvorexant, which gained little attention while in clinical development, joins osteoporosis drug odanacatib, the anesthesia-reversing Bridion, an anti-hardening of the arteries drug dubbed Tredaptive and a vaccine called V503 as among the pharma giant's brightest hopes."
Abbott stands to be hit hard due to the patent cliff, as it loses patent on its Humira and Keletra treatments in the next couple of years.
Humira treats rheumatoid arthritis and is the world’s best-selling drug in the autoimmune market with an estimated market share of over 30%, with revenues expected to top $10 billion by 2013. Keletra, whose patent will expire in 2016, is an antiviral used to treat HIV, and holds an 8% market share in the $18 billion HIV antiviral market.
By 2016 both drugs will be off patent--and Abbott will need some highly promising treatments to maintain its stature and economic clout.
Currently Abbott has over 20 compounds in Phase II or Phase II clinical trials. Perhaps its most promising is a hepatitis C regimen, which can be taken orally, as opposed to the current injectable treatments.
Viral hepatitis is one of the main causes of chronic liver disease in the U.S. There are approximately 19,000 new infections each year in the US. More than 3 million people are chronically infected with hepatitis C virus in the US and around 170 million people worldwide. According to Abbott, over 350,000 people die from hepatitis C-related liver diseases each year.
Abbott's experimental drug regimen suppressed the hepatitis C virus in the majority of patients in their latest clinical trial. So Abbott is focusing its planning on a combination of three drugs (ABT-450, ABT-267, ABT-333) that are now moving into larger, late-stage clinical trials.
In fact, the trial was so successful that the treatment knocked out the virus in 99% of patients with the liver disease. Assuming newer trial results are strong, and they receive FDA approval, they'd like to start selling the drug therapy in 2015.
With the market for new hepatitis C treatments possibly reaching the $20 billion mark by 2020, a number of companies are in a race to find the best one.
With 11 treatments in Phase I trials, 8 in Phase II, and 13 in Phase III, Bayer has a strong pipeline.
By far the most interest currently, given that the latest reports came out October 21st, is rociguant (BAY 63-2521), which has had good news from its ongoing Phase III clinical trials of the treatment for pulmonary arterial hypertension, also known as PAH. PAH is a progressive condition that overburdens the heart.
Trials indicate subjects had improved heart function and could better tolerate physical exercise. Patients on riociguat improved their walking distance by 36 meters on average, while those on placebo showed no improvement.
Professor Hossein Ardeschir Ghofrani of University Hospital Giessen, the principal investigator, was quite pleased with the results and explained the value of the measurement. "The six-minute walk distance test is a well-validated clinical measure in patients with PAH, and therefore, the results of the PATENT-1 trial are encouraging. . .These data from the PATENT study suggest that riociguat may be a potential treatment option both for patients who have never been treated for PAH as well as for those who have received prior treatment."
Although Bayer put forth no sales estimate for the treatment, analysts predicted 2017 sales from riociguat of $480 million.
3 Schizophrenia Compounds From Smaller Companies
Three smaller companies are both putting their hopes on new drugs to treat schizophrenia, an illness that affects 1% of the general population. Given that there are over 2.1 million cases in the U.S., a new, effective drug has blockbuster potential.
A small Israeli company, BioLineRx, is sitting on something exciting in its pipeline--so much so that shares in the company jumped 11% in early October after results from a new clinical trial were released.
It's a new drug for the treatment of schizophrenia. It has demonstrated efficacy, without the extrapyramidal symptoms (EPS), which include akathisia, parkinsonism, and abnormal muscle tone and spasms, common with first-generation antipsychotics like Haldol and Thorazine, and also without the metabolic side effects from the second-generation antipsychotics, like Zyprexa and Seroquel. Additionally it may improve cognition, a tremendous boon in schizophrenia treatment.
BloombergBusinessweek reported that compound BL-1021 was even more effective than the well-established Risperdal (risperidone), and patients had significant cognitive improvement while taking it. BioLineRx writes, "Trial results indicate that patients treated with the 20-30mg dose of BL-1020 exhibited a clinically relevant and statistically significant improvement of 9.27 points [on a cognitive test] as compared to the placebo group (6.01 points) and the risperidone group (6.2 points)."
On September 24, the U.S. Patent and Trademark office gave a patent to BL-1020, which will last through 2031.
Additional data from clinical trials is expected next year.
Omeros Corp filed an Investigational New Drug Application for its schizophrenia drug OMS824, which means they had successfully completed all the preclinical trials. Seeking Alpha claims this drug also has the potential to be a blockbuster.
PDE10 is an enzyme found in the brain in patients with diseases that affect cognition, including schizophrenia and Huntington's disease. Cognitive dysfunction is a major contributing factor to disability in these illnesses. OMS824, according to YAHOO! Finance, "inhibits PDE10 and is being developed for the treatment of cognitive disorders, including schizophrenia where OMS824 could also have a beneficial effect on the positive and negative symptoms of the disease."
In early October the FDA cleared the application, allowing Omeros to begin Phase I clinical trials, which study healthy subjects, evaluating the drug for safety and tolerability. Omeros is hoping to have initial data before the end of the year.
Alexza Pharmaceuticals Ink focuses on acute treatments for central nervous system conditions.
Its major innovation is the Staccato system technology, which vaporizes a drug into an aerosol that can then be inhaled for rapid system delivery, significantly increasing therapeutic onset.
The products are rapidly absorbed into the patient's circulatory system within three-to-five minutes of respiration. While it's true that intravenous drugs are faster, this treatment is non-invasive.
Alexza has been working for years on its treatment for the acute agitation of schizophrenia or bipolar disorder I called ADUSAVE (Staccato loxapine).
The drug successfully completed two Phase 3 trials: a 344-patient trial for schizophrenia and a 314-patient trial for bipolar disorder. Results from both were more than satisfactory.
The FDA has sent the treatment back twice over safety concerns, but Alexza is convinced that the third time is a charm, and hopes for approval by December of this year. They aim big, too.
Alexza's CEO and president, Thomas King, is unguardedly optimistic about the treatment's earning potential. He says, "In the US, Adasuve will be approved for use in a hospital setting to treat agitation in adult patients with schizophrenia and bipolar I disorder. . . .We believe that the Adasuve market potential in this hospital setting is more than $200mm per year."
Of course all of these companies hold out high hopes for the drugs in their pipeline--they have dedicated years and millions of dollars to getting them there. But it is only the rare lucky few drugs that make it out of the pipeline, into the market, and create revenues that fully satisfy pharmaceutical companies still smarting from losing patent on their biggest sellers.