Antimicrobial-resistant pathogens now claim almost 50,000 lives each year just in the US and Europe.
The Wellcome Trust has warned -
"We are failing to contain the rise of resistance, and failing to develop new drugs to replace those that no longer work."
A progress report by the Transatlantic Taskforce on Antimicrobial Resistance in May noted -
[ Developing new drugs alone will not be sufficient to address the growing resistance problem ... the efficacy of existing drugs needs to be preserved. Promoting the appropriate use of antimicrobial agents - use that maximises therapeutic effect while minimising the development of AMR ... is key to reducing selective pressure that leads to the development of resistance. ]
The treatment of pulmonary infection by tablets or injections is far from ideal. Gradual delivery of antibiotics via the bloodstream creates the ideal conditions for antimicrobial-resistant bacteria to emerge.
With infection by mycobacteria the problem is exacerbated by their ability to inhabit the pulmonary macrophages whose job it is to destroy bacteria. Infection by antimicrobial-resistant Mycobacterium Tuberculosis (TB) or Nontuberculous Mycobacteria (NTM) is treated for a minimum of eighteen months.
However on June 18 the FDA awarded Breakthrough Therapy status after 29 of 52 patients with chronic antimicrobial-resistant NTM infection tested negative during treatment with amikacin delivered via inhaled liposomes, 15 of whom did so after just one month.
Amikacin and the other aminoglycosides are classed as Crtically Important Antimicrobials by the World Health Organisation as they provide -
"Sole or limited therapy as part of treatment of ... Multi-Drug Resistant (MDR) tuberculosis."
The analysts are pretending not to have made the connection between efficacy in NTM and efficacy in TB.
MDR-TB infection Worldwide is estimated at 630,000. Just 30,000 using Arikayce will increase the current market valuation by a multiple of ten.
For those looking for another Apple - update as of Friday September 19:
On August 11 the Company guided via a preliminary prospectus that it intended to offer "up to $80,000,000 of shares", with underwriters having an option to purchase an additional $12,000,000 of shares within 30 days.
On August 18 the Company announced that it had issued shares to the value of $115,143,750, including the exercise of the option in full, at $11.25 per share.
From the 18th to the 20th the share price never dropped below $13.31, and was $13.50 or higher for most of the time.
Doesn't that seem rather generous on the part of bidders targeting ten million freshly issued shares - to offer new owners an immediate profit of 20%?
The Company now has sufficient cash to fund operations at the current burn rate until the second half of 2016.
Barring a problem with the marketing authorisation application, Arikayce is due to be launched in Europe in the second half of 2015.
Friday's closing price of $13.21 x 49,511,389 shares gives a present valuation of $654,045,449.
12,000 patients x $30,000 would generate annual sales of $360,000,000.
A multiple of 18.17 would deliver a valuation of $6,541,200,000.
How likely is it that doctors treating at least 12,000 of the 12,000,000 with TB Worldwide will have the funding to substitute Arikayce for one (or more) of the antibiotics responsible for the cumulative toxicity of the present regimens?
A Q1 snapshot of pharmas valued $4 billion - $9 billion with positive earnings:
Company ..... Market value ... Multiple ... Q1 sales x 4 ... Q1 v 2013 ... Q1 v Q4
PCYC ........ 9,260,454,870 ... 19.39 ...... 477,508,000 ....... +84% ......... -3%
BMRN ........ 8,914,668,090 ... 14.71 ...... 606,208,000 ....... +11% ........ +3%
JAZZ .......... 8,405,163,576 ..... 8.51 ...... 987,676,000 ...... +13% ......... +5%
SLXP ......... 8,576,659,274 ..... 5.58 .... 1,537,496,000 ...... +65% ....... +49%
TARO ......... 6,224,852,021 ..... 8.31 ...... 748,800,000 ........ +2% ........ -12%
MDVN ........ 5,834,953,246 ... 16.73 ...... 348,756,000 ...... +28% ........ -10%
QCOR ........ 5,672,223,163 ..... 6.24 ...... 908,416,000 ...... +14% .......... -6%
CBST ......... 4,643,326,216 ..... 4.44 ... 1,044,932,000 ......... -1% ........ -13%
UTHR ......... 4,475,054,784 ..... 3.87 ... 1,157,612,000 ........ +4% ......... +0%
ITMN .......... 4,520,936,978 ... 37.33 ...... 121,096,000 ...... +72% ....... +18%
Presumably a few would have had higher sales multiples but for disappointing Q1 numbers. SLXP has a low multiple primarily because an acquisition delivered the bulk of the recent increase in sales.
The confirmation that the EMA considers the Arikayce NTM data adequate evidence of efficacy opens the door also to off-label sales in MDR-TB (starting this time next year, assuming accelerated assessment).
Provided the strain is not amikacin-resistant, and funding permitting, Arikayce seems an obvious choice over injections that cause kidney damage and loss of hearing.
And the big players definitely wouldn't want retail investors to realize just yet that the risk/benefit argument for Arikayce trumps that of EVERY antibiotic currently available to a Worldwide TB population of 12,000,000.
12,000 using Arikayce at $30,000 per course would generate sales of $360,000,000.
A market value of $6,510,747,650 - ten times Friday's valuation - would require a sales multiple of 18.09.
If the EMA does grant accelerated assessment it will be confirmation it sees more here than just a better therapy for two small patient populations.
At least we know for sure the EMA views Arikayce as a better way of using amikacin -
[ The sponsor presented early clinical data showing better lung penetration and lower incidence of side effects as compared to the existing intravenous formulation. The Committee considered that this can translate into a clinically relevant advantage for patients affected by nontuberculous mycobacterial lung disease, as there are well-known and documented side-effects of the existing intravenous formulation that limit its use. ]
The FDA's decision to request an additional study was myopic at best when one considers the decision to approve bedaquiline for MDR-TB, subject to a confirmatory study, on the basis of Phase II culture conversion data.
In that case the FDA was prepared to overlook an unexplained substantially higher mortality rate in the patients on bedaquiline compared with those in the placebo arm, with the following rationale -
[ Nonetheless, treatment for resistant TB is complex, costly, toxic and prolonged, requiring at least 5 second-line drugs for up to 2 years. Second-line drugs include injectable drugs (amikacin, kanamycin, capreomycin) and oral fluoroquinolones (FQs) and other second line drugs; the optimal use of which has not been well studied in randomized controlled trials, and whose safety when used in concert with various doses and regimens is not sufficiently described. ]
Given the FDA's expressed concerns regarding the unquantified safety risk posed by co-administration of several drugs in MDR-TB, one would have thought it obvious that the Arikayce NTM data are "reasonably predictive" of a clinical benefit in MDR-TB - promising the removal of one or more drugs with the potential to contribute to cumulative liver toxicity.
I doubt the physicians treating these patients will overlook that aspect.
Exactly, aapl will be the first 1T company! Believe it or not. It is predestined, at this point it would take something catastrophic to prevent this inevitability. Just take your rickshaw and move along there is nothing for you here.