Transcript Overcoming Patent barriers to hepatitis C

Overcoming Patent barriers to hepatitis C
treatment
The Hepatitis C Treatment Revolution
Expanding Access to HIV Co-Infected and Beyond
UNITAID, MSF, WHO
IAC, Melbourne 21 July, 2014
Drugs of Interest - Hepatitis C
Sofosbuvir
Will likely be backbone of HCV all-oral pan-genotypic regimens
MSF planning to use in our treatment programs
Daclatasvir
Significantly strengthens sofosbuvir regimens and likely reduces duration
Potential component (e.g. with sofosbuvir) of pan-genotypic all oral regimen
Very good activity in genotype 3
Ledipasvir
Potential for pan-genotypic all-oral regimen (e.g. with sofosbuvir) – but need to
evaluate further studies that are on-going
potential for FDC with sofosbuvir for GT 1 and 4 – data already available
GS 5816
Very good pan-genotypic potential, but need to see results of on-going studies
Local Patents linked to Local Prices
Patent
No patent
One supplier
Multiple producers
No competition
Competition
High prices of
imported medicines
Access to low cost
generic medicines
Study by Andrew Hill – Minimum cost
to cure HCV with generic DAAs
Sofosbuvir (preventing evergreening)
DESCRIPTION
PCT Number/ PCT Publication Number (WO)
Patent No. 1
Base compound
WO2005003147A2
Patent No. 2
Structural formula and pro-drugs of nucleoside
derivatives + processes
(ex: salts, hydrates, solvates, steroisomers, and
crystalline forms)
WO2008121634A2
Patent No. 3
Process
WO2011123668A2
Patent No.4
Process for preparation of active compound
WO2011123645A2
Patent No. 5
Product byprocess
WO2010135569A1
Patent No. 6
WO2011123672A1
Specific derivative in crystalline or crystal-like form
Patent No. 7
Combinations exhibiting synergistic effects +
methods of use
WO2013040492A2
Patent No. 8
WO2013082003A1
Composition of sofosbuvir + at least one excipient
THE GROUNDS FOR OPPOSING PATENT APPLICATIONS ON SOFOSBUVIR
24 Nov 2013: opposition to the patent application
on the pro-drug
The opposition, filed at the Kolkata Patent Office by
I-MAK targets Gilead’s patent application
3658/KOLNP/2009 (WO2008/121634).
19 March 2014: opposition to
the patent application on the base compound
The opposition, filed at the Delhi Patent Office by IMAK and the Delhi Network of Positive People
(DNP+) targets Gilead’s patent application
6087/DELNP/2005
(WO 2005/003147).
Lack of novelty - The base compound has been disclosed in various earlier
patents, which already reveal the free base compound that is used
in sofosbuvir
The complete patent opposition documents are
available.
The treatment regime MSF doctors dream of!
Which DAAs
• Sofosbuvir + Daclastavir (NUC + NS5a)
• pan-genotypic
• Better treatment outcomes for patients with
advanced liver disease
In what form?
• Co-blister
• Fixed dose combination
• Pediatric formulation
The barriers
• Clinical trials - Gilead won’t cooperate with BMS
• Then we wait for sofosbuvir and daclastavir to be registered
separately
• Generic production of sofosbuvir in the pipeline
• Generic production of daclastavir? Dialogue with generic producers
needed to stimulate interest.
• Likely scenario – sofosbuvir will not be patented in India.
Daclastavir (at least compound) could be patented…(impact of new
patent regime in India)
• Challenge – how do you ensure generic supply of sofosbuvir and
daclastavir together for medical projects
What TRIPS flexibilities?
 Finding the patent applications (WHO and I-MAK)
 Filing pre-grant oppositions (starting with India)
• If and when a patent is granted on daclastavir, use of bolar provision will
protect generic companies from infringement suits for developing,
registering and pre-qualifying (BE & stability studies) of generic
formulations of daclastavir (section 107A of Indian law)
• Compulsory licensing for daclastavir (building a dossier for Indian
government and placing an order)
• Can the drug be produced in an LDC (using the LDC extension for opening
up generic supply of new DAAs patented in India
What are governments doing about this?
Generic competition or tiered pricing
short term gain – long term pain
300000000
250,000,000
Total Cost of Treating 50000 patients
250000000
200000000
150000000
100000000
50000000
Generic
competition
45,000,000
900$
5000$
10,000,000
0
1
2
Cost of new DAA
3
Marketing authorization/Registration status in India
•
Registration in developed countries - On the two drugs (sofosbuvir & simeprevir)
despite having completed phase II trials (phase 3 data is awaited), were considered for
accelerated approval by the USFDA & EMA as they appear to offer significant advantages
over available therapies. Another drug daclastavir is also likely to receive approval in
August 2014.
•
Local registration - For new oral drugs to be available in the India market, first
companies (originator or Indian generic company) have to submit registration dossiers to
the Indian Drug Regulatory Authority (Drug Controller General of India). This is yet to
happen and therefore the drugs are not available locally. In India.
•
Gilead is yet to apply for registration of sofosbuvir. As per the Indian law – the Drugs &
Cosmetic Act - it is doing a local trial covering 100 patients. Therefore registration of
sofosbuvir in India is unlikely in 2014. Maybe 2015 if the Indian FDA does not delay.
•
Gilead will submit its dossier only after completion of the local trial. For other drugs like
daclastavir and simeprevir we are unaware if the companies have initiated any steps to
register these drugs or conducting clinical trials in India. Generic companies too could
initiate the registration process but till now no company has stepped forward to do so.
• More and more patients failing current
treatment regimen (Peg inf+Ribavirin) are
being prescribed new DAAs (Sofosbuvir) and
asked to import from US if possible (cost
26,000 canadian $ for 28 tablets)
• Cases of denial of treatment starting to emerge
(human rights issues).
Compassionate use
• What is the option for patients who need new HCV
drugs immediately: Compassionate use allows the
possibility to use (outside of clinical trials) by a clinician
a new drug yet unregistered in India for patients suffering
from a life threatening disease and for whom
conventional therapies have failed.
• In other words, when no other treatments are available to
a seriously ill patient, clinicians can sometimes use a new,
unapproved drug. Such provisions are mainly used by
Indian clinicians for diseases like cancer to provide access
to treatments that are still under development and that
have not yet received marketing authorization in India.
Compassionate use
• For patients who have either failed or cannot tolerate
treatments based on interferon injections and are in urgent
need of treatment there are legal safeguards in the Drugs &
Cosmetic Act that allow access to new drugs which are yet
to be registered in India.
• Please note that Indian law does not directly recognize the
concept of compassionate use but clearly allows for use of
new unregistered drugs imported under a special license in
small quantities for life threatening diseases or such disease
requiring therapies for unmet medical needs.
Compassionate use
There are three steps to this process:
• Step 1
• Applying to the company for compassionate use – does the
company accepts the request for compassionate use for this we
must identify whether the company (for sofosbuvir it is Gilead,
for simeprevir its is Janssen and for daclastavir is it BMS) have
a Compassionate Use program open to process requests.
• Gilead’s criteria for CU –only those who have had liver
transplant are eligible
• Janssen setting up a compassionate use programme for Asia
• Daclastavir - BMS - ?
Compassionate use
•
•
•
•
•
•
•
•
Step 2
Once the company responds affirmatively then the patient must apply to the Drug
Controller General of India for permission –
The new unregistered drug can be imported under Rule 36 (import of drugs for
personal use), by filing and submiting form 12A (Application for the issue of a
permit to import small quantities of drugs for personal use). Form 12A is to be
filled by the patient (attaching the prescription of the doctor.)
the DCGI grants permission under 12B (Permit for the import small quantities of
drugs for personal use.
Apply for waiver of custom tax to MoH
If granted this will be sufficient to legally import the drugs.
Step 3
Once the drug has been dispatched by the company, the import shipment
(consignment of the drug) has to be custom cleared and picked up from the
airport with the original Import Permit (12B Form) and other necessary
documents.