March 2018 Catch Up: What’s Been Happening in the Pharm World?

What drugs hit in 2017? How did approvals compare to 2016?

By Michael Jorrin, "Doc Gumshoe", March 14, 2018

[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investment ideas. His ideas, thoughts and words are his own, and you can see all his past pieces here.]

In comparison with 2016, which was on the whole a rather sluggish year in terms of signal events such as new drug approvals from the FDA, 2017 started off with a burst of activity which continued right through the year.   While there were only 22 approvals in 2016, in 2017 there were a total of 55 new approvals.   Of these, 46 were what the pharmaceutical industry calls “simple molecular entities,” 6 were biologics, 2 were CAR-T gene-tinkering procedures, and one was a new shingles vaccine.   In case you’re wondering, the term “biologics” is used to categorize a class of drugs that are not synthesized in the lab from other chemicals, but are generated by living cells of some kind, such as yeast, some bacteria, or, with increasing frequency, from Chinese hamster ovaries.   This makes them more expensive and difficult to duplicate.   Biologics have turned out to be the drugs that most effectively treat some autoimmune diseases such as rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis.

The disease state in which the greatest number of drugs gained approval was cancer.   Fourteen drugs in total got the accolade in this category.   In almost all cases, the cancers for which drugs were approved were quite narrowly defined.   For example, Idhifa (enasidenib), from Celgene/Agios was approved for treatment of relapsed or refractory acute myeloid leukemia (AML), and Responsa (inofuzumab ozogamicin) from Pfizer got the nod for treatment of relapsed or refractory acute lymphoblastic leukemia (ALL).   Yescarta (axicabtagene ciloleucel), which Gilead got when they acquired Kite, was approved for treatment of relapsed or refractory large B-cell lymphoma, and Calquence (acalabrutinib), from AstraZeneca, for mantle cell lymphoma.   Kisqali (ribociclib), from Novartis, and Verezenio (abemaciclib), from Eli Lilly, gained approval for both HR-positive and HER-2 negative breast cancer – a somewhat broader indication – but Nerlynx (neratinib), from Puma Technology, got the nod only for recurrence of HER-1 positive breast cancer.

Merck KGaA and Pfizer have teamed up in the development of Bavencio (avelumab), which has so far won approval in two niches – Merkel cell carcinoma, which is quite rare, and also advanced urothelial carcinoma, which is a common bladder cancer.   In addition, they have gotten some positive results in several other cancers – non-small-cell lung cancer, ovarian cancer, and kidney cancer.      Bavencio is a check-point inhibitor, targeting the programmed cell death ligand PD-L1, which is normally active in suppressing autoimmune function.   Thus Bavencio can be said to enable programmed cell death in cancerous cells.

It goes without saying that when a pharmaceutical outfit gets a drug approved for a narrow niche, that is by no means the culmination of their hopes and ambitions.   It’s more like a firm foothold at the base of a steep climb to a summit, which would be approval for treatment, either alone or in combination with other agents, of a much larger range of cancers.   And, indeed, this is a distinct possibility.

In previous homilies, I have discussed how of necessity pharmaceutical companies go about designing clinical trials in the cancer area.   It would be stupid – the only word for it! – to try launch a clinical trial in which a new candidate drug went up against an established first-line cancer drug in the treatment of a common class of cancers.   For one thing, the trial would never, never, never get approval from the FDA.   What, are you proposing to do a clinical trial in which half the subjects, all of whom are in the clutches of a deadly disease, are denied treatment with the best drug currently available?   No dice!   It becomes a good deal more feasible if the proposed study population consists of patients who have failed treatment with the first line drug, and perhaps also with a couple of drugs after that.   So the pharmaceutical company is left with a patient population for the trial that is, by definition, harder to treat, and also, due to the unfortunate circumstance that they have failed previous treatments, considerably sicker.

If, under those circumstances, the candidate drug demonstrates some even mildly positive results, there is reason to suppose that in easier-to-treat patients who are in earlier stages of the disease, the candidate drug might achieve significantly more positive results, and this does sometimes happen.   The pharmaceutical companies definitely pin their hopes on that.

It makes good business sense for pharmaceutical companies to devote resources to the development of new cancer agents.   Leaving the statistics aside, cancer scares people a lot more than heart disease does, and “curing cancer” is a common battle cry in the health-care field.   One doesn’t hear drug companies or hospitals proclaiming that they are launching a drive to “cure heart disease.”   Of the 55 agents approved in 2017, only one had any relationship with cardiac issues.   That one, Giapreza (angiotensin II) from La Jolla Pharma, got the thumbs up as a drug for adults in shock who manifest dangerously low blood pressure; the angiotensin gets their heart to contract a bit more vigorously.   We have to recognize that quite a lot of progress has been made in addressing cardiac-related issues, ranging from elevated cholesterol and blood pressure to dealing with cardiac arrhythmias and even up to and including heart transplants.   Unfortunately, comparable progress has not been made in treating cancers.

In the infectious diseases are, there were only seven drugs that could be classified as antimicrobials/ antibiotics, and of these, only one was approved as being broadly effective in a class of infections.   That one was Baxdela (delafloxacin), a fluoroquinolone from Melinta Therapeutics, which got the nod for treatment of acute bacterial skin and soft tissue infections (ABSSSI).   This is a broad and somewhat difficult category, since the pathogens that cause these infections often mutate into drug-resistant variants, including the notorious methicillin-resistant S. aureus and resistant E. coli types.   Baxdela is effective versus both gram-positive and gram-negative pathogens, and is currently in a Phase 3 trial in community-acquired bacterial pneumonia.    The other antimicrobials won their approval in quite narrow niches, such as Chagas disease, bacterial vaginosis, complicated urinary tract infections, impetigo, and the like.

At the end of this section, I am including a longish table listing all the 2017 approvals in chronological order, with (in some cases) estimated dollar figures for projected sales and cost to patients.   But before we get to that, there are a few more subjects in connection with the 2017 approvals that deserve a word or two.

What accounts for the surge in FDA approvals in 2017?

There are those who point their fingers directly at the FDA, leaping to the conclusion that the regulators have become easier and more friendly to the pharmaceutical companies.   Their reasoning is that the FDA has looked On High and decided that the winds were blowing in the direction of a more business-friendly regulatory environment.   Certainly in a general sense the breezes were pointing the weathervane in a somewhat different direction, but I don’t get a clear indication that the FDA was much influenced by those wandering breezes.   A lot of the work of overseeing the tedious progression of a candidate drug through the approval process takes place at a workmanlike level that considers the NDA (new drug application) in meticulous detail which has little to do with top-down policy decisions.   And, in case you’ve forgotten, even in 2017 the regulatory landscape was littered with the wreckage of drugs that failed or were rejected by the FDA.

Another possibility is that pharmaceutical companies had been going slow in 2016 and previous years in response to the push-back concerning high drug prices.   As it turned out, a lot of the heat was focused on a few outliers who raised the prices of previously inexpensive existing drugs by large factors.   One example is the out-and-out malefactor Martin Shkreli, who raised the price of Daraprim from $13.50 to $750 per tablet.   Shkreli, by the way, has been convicted on three of eight charges of securities fraud and has just been sentenced to seven years in the hoosegow.   Raising the price of Daraprim – not a newly-discovered drug by any means – was not involved in the charges against him, but his history did not elicit any sympathy from the judge.

Pharmaceutical executives have been fairly quick to distance themselves from Shkreli, and it may have been handy to be able focus the outrage on a single figure, or a single drug company.   Valeant, for example, hugely raised prices on drugs it had acquired such as Nitopress, Isuprel, and Syprine, which in combination with accusations of other shady dealings, did great harm to the company.   This created an opportunity for pharmaceutical companies to say, “We are not Martin Shkreli!   We are not Valeant!   We work hard and lavish colossal sums developing drugs that have the potential to be life-saving for millions of people, and we’re only trying to keep our immensely valuable enterprises solvent!”

In general, there has not been much resistance to the price tags on new drugs, especially if they treat potentially fatal diseases.   For example, Roche’s Hemlibra (emicizumab) won its approval for treating hemophilia A in patients who do not respond to the standard treatment, which is a blood factor (recombinant factor VIII).   Many of these patients are children who could, if not receiving treatment, easily bleed to death from routine playground mishaps.   Because the consequences of non-treatment are dire and the potential patient population is, fortunately, fairly small, health insurers are going along with the projected price tag, which is $482,000 in the first year of treatment and $448,000 per year thereafter.

Which brings us to another crucial question:

How much will these new drugs cost?

Not all of the pharmaceutical companies have actually placed their new drugs on the market at this time nor yet announced what they would charge, but from what is now known, these drugs will not be cheap.   They will not even be moderately priced.   They will be Very Expensive, and in many cases their prices will be justified, if we can use that word without a blush, by the same general line of reasoning that justified Roche’s near half-a-million per annum price for its hemophilia drug.   For instance, Gilead’s Vosevi, which is a combo of previously well-established hepatitis C drugs, sells for about $25,000 a bottle, but since these drugs usually knock out hep C once and for all, there hasn’t been much fuss about the price.

Red flags are raised when there is a big price differential between the US and other countries.   For example, Marathon’s Emflaza (deflazacort) was approved to treat Duchenne muscular dystrophy, which also affects the young and is a severely disabling disease affecting a relatively small patient population.   The drug, deflazacort, is not newly discovered – it is a steroid introduced in 1969, and is used to treat a number of diseases including rheumatoid arthritis, lupus, and other immunologic conditions.   Marathon has priced it at $89,000 and then sold it to PTC Therapeutics, which cut the price to $35,000.   In the UK, however, one can buy a pack of 60 tablets for about $21.   This has caused raised eyebrows, to say the least.

Which 2017 drug approval gets the Blue Ribbon?

It would have to be Kymriah (tisagenlecleucel), from Novartis, approved for the treatment of acute lymphoblastic leukemia (ALL).   This is the first CAR-T agent to reach the market, but not the last, we hope.   It was formerly designated CTL 019, and on August 17, 2017, Doc Gumshoe wrote this about it:

“One of the pharmaceutical companies that is out in front is Novartis (NVS), which was awarded breakthrough status by the FDA on July 7 2014 for its CAR-T agent CTL 019, which it is developing in collaboration with the University of Pennsylvania.   In a study in children and young adults with recurrent or refractory ALL, 36 of 39 patients attained complete remission.   Novartis is a cancer powerhouse, with nine patented cancer drugs besides Gleevec, and many more in various stages of development.”

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Kymriah won approval for the treatment of B-cell ALL in children and young adults.   It will also be quite pricey – a course of treatment will run $475,000.   This does appear to be justified, and I use the term without quotation marks, by the exceedingly complicated procedure employed to create the agent.  Novartis has said that it will not charge patients who do not respond to treatment and points out that some bone marrow transplants are more expensive.

The treatment process takes about three weeks, specifically customized for each patient.   T cells from the patient are extracted from the patient’s blood, and the cells are modified by the new drug through a process that inserts a gene into the T cell.   The gene carries a chimeric antigen receptor (CAR) that targets the leukemia cells.

Novartis just barely beat Kite Pharma to the finish line.   Kite (recently gobbled up  by Gilead) got approval for a Yescarta (axicabtagene ciloleucel) not long after Kymriah got the FDA accolade.   Yescarta is also a T-cell modifier, approved for adults with relapsed or refractory large B-cell lymphoma.   The projected price for treatment with Yescarta is $373,000.

How do pharmaceutical companies calculate their prices?   And how should they?

It’s obvious that the price of the drug can’t just be based on what it costs the pharma company to manufacture the drug.   By a huge margin, the cost of developing the drug – from the first glimmer of hope that a particular molecular entity might have a beneficial effect all the way through lab research, clinical trials, and shepherding the drug through regulatory approval – greatly exceeds the actual cost of manufacturing the finished product.   Nor can the market price be based only on the sum of those two costs, because of the fairly high proportion of busts that pharmaceutical companies are required to stomach.   Sometimes these busts wallop the company after they have spent a billion or more in bringing the drug to the point where it’s time to test it against the competition.   And sometimes safety concerns compel the recall of a drug – most recently, for example, AbbVie and Biogen yanked their multiple sclerosis drug Zinbryta because of reports of serious inflammatory brain disorders including encephalitis, so there’s a billion or so down the drain.

So where it winds up is that the pharmaceutical companies will charge “what the market will bear.”   And this varies widely.   No matter how much it costs to develop, a drug that “sort of” controls hay fever or acne won’t support an exorbitant sticker price.   But a drug that reliably prevents little kids from bleeding to death from a minor cut, or definitively cures a disease that would otherwise be a life-long deadly threat is another matter.

“What the market will bear” depends to a great extent on whether the health insurers decide to cover the drug.   Not many private citizens are able to pony up the price of many newly-marketed drugs out of their own bank accounts, and insurers will look carefully at such matters as what other drugs might be available to manage that condition, what are the effects of that condition on patients, how many persons are affected by that condition, and who those patients might be.   In some cases, pharmaceutical companies make special arrangements for patients who cannot afford to pay for their drugs out of pocket and do not have insurance coverage.   And, of course, many people all over the world simply cannot get the drugs they need, and in some cases, need desperately.

Pharmaceutical companies routinely offer discounts to health insurers and providers such as hospitals, and these discounts have been increasing in size.   An analysis by Wells Fargo showed that the average sale rebate and allowance (how the discounts are referred to in the trade) has increased from 28% to 41% since 2012.   Some pharmas have increased their discounts at faster rates, including Eli Lilly, Johnson & Johnson, and Merck.

Is there another way to price drugs such that the individuals who need the drugs are able to get them, while at the same time providing enough money for the originating drug company to do the necessary research and development to keep the drug pipeline flowing?   Pricing drugs on the basis of outcome – or, at least partly on the basis of outcome – as Novartis has done with Kymriah  –  may be a partial solution.   Government programs to aid with the financing of drug development may be worth exploring.   And, of course, programs such as Medicaid to help the less affluent afford the medical care, including drugs, that they need.   I cannot imagine, however, that it would work well to have a single government behemoth handling the entire drug development universe.

… and who were the big winners?

Hands down, Novartis took the prize, with three new drug approvals, all in the cancer area.   AstraZeneca also did quite well, with three winners.   Several pharmas put two of their candidates across the finish line, including  Gilead, Pfizer, Novo Nordisk, Roche, Sanofi/Regeneron, and Valeant.   Roche’s Ocrevus (ocrelizumab) for multiple sclerosis is projected to bring Roche a sweet $4.1 billion return.

As you look over the list of new drug approvals below, you’ll notice a robust presence from the established players – the notorious Big Pharmas.   The biotechs show up, but in terms of scoring regulatory approval, they still have a way to go.

Chronological List of 2017 Drug Approvals

Drug name Company  Disease for which approval was granted Sales 


Cost of treatment 


Synergy Pharmaceuticals Chronic idiopathic constipation $1.0 – 1.5 B ?


Amgen Secondary hyperthyroidism NA


Marathon Duchenne muscular dystrophy $100 M $89,000


Valeant Psoriasis NA NA

(telotristat ethyl)

Lexicon Carcinoid syndrome diarrhea $350 M $61,000 to $72,000

(allergen extract)

Merck to ALK-Abello Dust mite allergy NA NA


Novartis HER-2 negative breast cancer $1.6 B NA


Newron Parkinson’s disease $500 M NA


Pfizer/Merck KGaA Bladder cancer, Merkel-cell carcinoma $4 B NA


Shionogi/Purdue Opioid-induced constipation NA NA


Tesaro Ovarian, fallopian tube, peritnoneal cancer $1.9 B NA


Sanofi/Regeneron Atopic dermatitis $3 B $37,000


Roche Multiple sclerosis $4.1 B $65,000 (with discounts)


Teva Huntington’s chorea $700 M $60,000


Neurocrine Tardive dyskinesia $1.3 B NA

(cerlipnase alpha)

BioMarin CLN2 disease $100 – $200 M $486,000


Ariad/Takeda ALK pos NSC lung cancer $1B + NA


Novartis AML $260 M NA


Radius Health Osteoporosis in postmenopausal women $450 M NA


AstraZeneca Urothelial carcinoma (advanced bladder cancer) $2.8 B NA


Mitsubishi Tanabe Amyotrophic lateral sclerosis (AML) NA $145,524 before discounts


Sanofi/Regeneron Rheumatoid arthritis $1 B $39,000

(nonacog β pegol)

Novo Nordisk Hemophilia β NA NA


Octapharma Congenital fibrinogen deficiency NA NA


Melinta Therapeutics Acute bacterial skin & soft tissue infections $400 M NA

(C1 esterase inhibitor

CSL Behring Hereditary angioedema NA NA


Portola Prevention of venous thromboembolism $1.7 B NA


J & J Plaque psoriasis $1.5 B NA


Puma Technology HER-2 pos breast cancer recurrence $1.25 B + NA

(sofosbuvir, velpatasvir, voxilaprevir)

Gilead Hepatitis C $1.1 B $24,920  (per bottle)


Celgene/Agios Relapsed/refractory AML $500 M $24,872 (per month)

(glecaprevir, pibrentasvir)

AbbVie Hepatitis C $1.25 B $26,400 (per treatment course)

(inofuzumab ozogamicin)

Pfizer Relapsed/refractory ALL $1 – 2 B NA

(human immunoglobulin)

Kamada/Kedrion Rabies NA NA

(meropenem, vaborbactam)

The Medicines Co. Complicated UTI $400 M NA


Chemo Group Mundo Sano & Drugs for Neglected Diseases Foundation Chagas disease NA NA


Novartis B-cell ALL in children & young adults NA $475,000


Symbiomix Therapeutics Bacterial vaginosis $100 M NA


Bayer Relapsed follicular lymphoma $600 M NA


Eli Lilly HR-pos, HER-2 neg breast cancer $1.3 B NA

(axicabtagene ciloleucel)

Kite/Gilead Relapsed/refractory large B-cell lymphoma $2 B $373,000

(zoster vaccine)

GlaxoSmithKline Shingles $1 B NA


AstraZeneca Mantle cell lymphoma NA $14,259 per month

(latanoprostene bunod solution)

Valeant Open-angle glaucoma/ocular hypertension NA NA


Merck Prevent cytomegalovirus after bone-marrow transplant $370 M NA


AstraZeneca Severe asthma $2.1 B $38,000, then $28,000 for six doses

(vestronidase alfa-vjbk)

Ultragenyx Mucopolysaccharidosis type VII $75 M $375,000 per patient/year


Roche Hemophilia A $2 B $482,000 in year 1, $448,000 py thereafter


NovoNordisk T2DM $2.7 B NA


Medimetriks Impetigo from S. aureus/Strep pyogenes NA NA

(netarsudil solution)

Aerie Pharm Open-angle glaucoma/ocular hypertension $443 M NA

(voretigene neparovec-rzyl)

Spark Therapeutics RPE65 mutation associated retinal dystrophy $381 M $1 M


Pfizer, Merck T2DM $2 B NA

(macimorelin acetate)

Aeterna Zentaris Diagnosis of adult growth hormone deficiency $70 M NA

(angiotensin II)

La Jolla Pharma Low blood pressure in adults with shock $500 M NA

As you glance over the list, you might notice that many of the suffixes of the chemical (non-trademarked) names of these drugs are similar.   Might they mean something, or are those just nonsense syllables strung together to confuse us?   Well, for example, the drugs ending in – ib are inhibitors of a physiologic agent that contributes to a disease process.   Those ending in mab are monoclonal antibodies, frequently biologics, that are primed to attack and disable invaders.   The suffix cin tells you that the drug is an antibiotic, the suffix vir that it’s an antiviral, and so on.   The other parts of the name may provide clues as to what the drug’s ancestry is.   Drug companies are understandably reluctant to reveal exactly what’s in their products, or how their products are manufactured, and sometimes refuse to sell their drugs to anyone but the patients to whom they are prescribed, to prevent competitors from copying their drug and marketing generic versions, despite regulatory protection.   But the competition figures it out pretty quickly, just the same.

Where does Doc Gumshoe come out?

My sober, reasoned conclusion on all this is that on the whole, the big increase in new drug approvals is good news.   Today’s outrageously expensive drug, approved for a tiny sliver of the patient population, will be increasingly used in combination with other drugs, and in a greater number of patients.   Consequently, it will drop in price, perhaps at first just a bit.   But before long, it will be reasonably priced, and eventually, dirt cheap.   Great numbers of patients may benefit.   Also, some drugs that were introduced with fanfare and then dismissed as being no better than the old hat drugs may be found to deliver genuine benefit.   Take Praulent, Sanofi/Regeneron’s PCSK9 inhibitor.   That class of cholesterol-lowering drugs was under a bit of a cloud due to the failure of Amgen’s Repatha (also a PCSK9) to come through with a benefit in terms of decreased mortality.   (It lowered LDL-cholesterol just fine, but patients on Repatha didn’t seem to get any benefit in terms of decreased mortality.)   But in the ODDYSEY trial, Praulent delivered 15% reductions in cardiac mortality and also in all-cause mortality, perhaps putting that class of agents back in the sunshine.   All in all, there seem to be rays of sunshine over the whole pharmaceutical field.

* * * * * * *

I intended this chapter of the utterances of Doc Gumshoe to cover a much greater number of relative small news items, but that single topic of the day swelled up out of control and took up the whole piece.   I’ll return to the news next time – and there are quite a few of them.   Thanks to all, Michael Jorrin (aka Doc Gumshoe)