Report Card Background Information
Issued by the
ATAC Drug Development Committee
September 10,
2009
Abbott Laboratories
HIV Drugs:
Kaletra (lopinavir/ritonavir)
Norvir (ritonavir)
Pipeline:
Abbott has no new HIV drugs in
development though it is developing a new tablet form of Norvir. Three drugs to
treat hepatitis C virus (HCV) are in clinical development.
Demographics of clinical trials:
The FDA approval trials for Kaletra
were completed over a decade ago. The 863 trial in treatment-naïve patients
enrolled 20% women and 43% non-white participants. The 888 trial in patients
with prior exposure to a protease inhibitor enrolled 14% women and 32% non-white
subjects. Subsequently Kaletra has been studied in a wide range of populations,
including pregnant women for prevention of mother-to-child transmission of HIV.
Interactions with the HIV treatment community:
Abbott has consulted with the
European HIV treatment activist community on trial designs for HIV. It has
consulted with community representatives on HCV drug development.
Abbott holds an annual meeting with
a community advisory board and consults with individual treatment activists on
an ad hoc basis. ATAC refuses to meet with Abbott formally, due to the 400%
price increase of Norvir in 2003.
Abbott has not included members of
the community on its safety monitoring boards for clinical trials.
Access:
Abbott has a patient assistance
program (PAP) for Kaletra and Norvir to facilitate access for those who cannot
afford them. Abbott’s co-pay assistance program covers Kaletra, but not Norvir.
The Kaletra expanded access program
opened nearly one year prior to approval. Clinical trial participants continued
to have drug access after approval until other payers—or the PAP—became
available.
Abbott has provided drugs to some
outside investigators but has not provided free Norvir to government-sponsored
trials of protease inhibitors that did not involve Kaletra.
Pricing:
Kaletra is the lowest-priced
product in the HIV protease inhibitor class. Norvir is the highest. In 2003,
Abbott announced that it was increasing the price of Norvir by 400% to “reflect
its value” as a boosting agent. Norvir was approved at a much higher dose as a
protease inhibitor but is no longer used for that purpose. The boosting dose is
much lower. The re-pricing of Norvir resulted in a storm of protest from HIV
treatment activists and doctors.
Abbott has met with the Fair
Pricing Coalition prior to setting prices for new products.
Abbott kept the price of a newer
formulation of Kaletra the same as that of the formulation it replaced. A new
formulation of Norvir is expected to be approved in Fall 2009, but no price has
been announced.
Boehringer
Ingelheim
Drugs:
Viramune (nevirapine)
Aptivus (tipranavir)
Pipeline:
Boehringer Ingelheim (BI) has
several novel first-in-class HIV compounds in the preclinical development
stage. It is conducting a study on an extended release formulation of Viramune.
BI currently has a hepatitis C
polymerase inhibitor and an HCV protease inhibitor in early clinical
development.
Demographics of clinical trials:
Viramune FDA approval studies were
conducted in the early 1990s. These trials consisted of about 21% female and
30% non-white volunteers. The Aptivus pivotal trial program was conducted in
the middle part of this decade and enrolled about 15% female and 25% non-white
participants
The FDA asked for no additional studies
related to gender, race, or ethnicity at the time of Viramune’s accelerated
approval. Subsequently, for the drug’s traditional approval, the FDA requested
analyses of clinical trial data for potential factors associated with liver
toxicity, such as gender and race.
At the time of the accelerated
approval of Aptivus, BI made a post-marketing commitment to evaluate Aptivus in
diverse (racial and gender) populations and BI commenced the study. However,
due to an inadequate number of eligible patients who were willing to enroll,
the FDA subsequently released BI from its commitment and the study was
terminated.
Interactions with the HIV treatment community:
Though BI meets with selected
members of the treatment activist community, it does not meet formally with
ATAC. Therefore, the wider community of treatment activists has not had
opportunities to provide input on trial design. In the past this has resulted
in ATAC members voicing objections to trial designs after it was too late to
alter protocols.
BI offered a small group of
selected activists input on some studies of Viramune and on the Aptivus RESIST
trial. Though a few community members were asked to provide advance input on
the SPRING trial, there was no opportunity for the general ATAC membership to
express opposing ideas until after the trial launched. BI has not met with ATAC
since 2004, despite several invitations to do so.
BI does seek some community input
through yearly community advisory board meetings. Some ATAC members have
attended these meetings, though not formally as representatives of ATAC. They
report that the advisory board focuses primarily on existing products and
marketing concerns and does not offer the opportunity for significant
discussions about clinical trial design during the planning stages.
Access to medications:
BI has a patient assistance program
(PAP) for patients who lack insurance coverage for pharmaceuticals and who meet
certain household income levels. BI did not have a co-pay assistance program at
the time these grades were assigned, but says it is launching such a program
later in 2009.
Drug access has been continued for
clinical trial participants until a drug is approved and other payers—or the
PAP—become available.
BI collaborates with NIH-funded
clinical research networks to make its medications available for clinical
trials.
Pricing:
Although Viramune is priced lower
than Sustiva or Intelence, regular price increases have been taken, resulting
in the second highest annual rate of increase (>10%) for any HIV medication.
Aptivus is the second highest
priced protease inhibitor. But since it must be taken with Norvir, the combined
price of the two drugs makes Aptivus/Norvir the most expensive protease
inhibitor component of a regimen.
BI continues to meet with the Fair
Pricing Coalition regarding drug pricing.
Price freezes for both Aptivus and Viramune remain in effect for all state AIDS
Drug Assistance Programs to help ensure that the products are accessible to HIV
patients in need.
Bristol-Myers Squibb
Drugs:
Zerit (stavudine)
Sustiva (efavirenz)
Videx (didanosine)
Reyataz (atazanavir)
Atripla (efavirenz, tenofovir, emtricitabine) [joint
venture with Gilead]
Pipeline:
Bristol-Myers Squibb (BMS)
currently has an HIV integrase inhibitor and an entry inhibitor in very early
phases of testing. The company also has three hepatitis C compounds in phase I
studies.
Demographics of clinical trials:
BMS has been conducting clinical
trials of HIV drugs since the late 1980s. Early trials were conducted almost
entirely in white male populations, though subsequent trials have recruited
more women and people of color. Roughly 30% of participants in the recent
CASTLE study were women. This was an international study and there were
significant numbers of African Americans in the study as well. Previous studies
sponsored by BMS have been less successful in recruiting women and people of
color, though no worse than those of most other companies.
Interactions with the HIV treatment community:
In the past, BMS consulted
frequently with the HIV treatment activist community, though not always with
sufficient advance notice to allow changes in protocols if necessary. This
cooperation lasted through the development of Reyataz (atazanavir) in the early
2000s. Subsequently, BMS stopped meeting with the DDC and only recently began
meeting again. The company has not yet formally committed to meeting prior to
the launch of phase II and phase III studies.
BMS holds advisory boards yearly
that include members of the community that the company selects. Though drugs in
the pipeline have been discussed at a few meetings, most have focused on HIV
treatment education, marketing, and public policy.
BMS has not included members of the
community on its safety monitoring boards.
Access:
BMS has a patient assistant program
(PAP) to facilitate access to its marketed medicines for those who cannot
afford them. BMS also offers a co-pay assistance program. It also has a co-pay
assistance program for people with private insurance who use Atripla. It covers
co-pay costs whenever they exceed $50 per prescription, up to a maximum of $200
per prescription per month. This co-pay plan requires one of the largest
initial out-of-pocket patient contributions of all the existing programs but Gilead’s, which has the same criteria.
Drug access has been continued for
clinical trial participants until a drug is approved and other payers—or the
PAP—become available.
BMS provides its drugs to outside
investigators. BMS’s expanded access programs have had launch dates that range
from only a few months prior to approval to approximately one year prior to
approval.
Pricing:
Reyataz was the first drug launched
by BMS since Zerit (Sustiva was launched by Dupont). Reyataz was launched at a
price significantly higher than its nearest competitor, Kaletra. The price of
Atripla was the same as the price of Sustiva and Truvada combined. BMS has
taken annual price increases of approximately 6% on its drugs.
BMS has met with the Fair Pricing
Coalition prior to launching new drugs and also to discuss price increases of
approved drugs and the development of a co-pay assistance program.
Gilead Sciences
Drugs:
Viread (tenofovir)
Emtriva (emtricitabine)
Truvada (tenofovir/emtricitabine)
Atripla (efavirenz/tenofovir/emtricitabine) [joint
venture with BMS]
Pipeline:
Gilead has an active HIV development pipeline that includes an
integrase inhibitor; a combination, four-drug single-pill regimen; a boosting
agent and drugs to treat hepatitis C virus. It also develops and studies other
products for people with HIV-related infections, for HIV-related cancers, and
for prevention of HIV infection. Gilead provides drugs for trials of Viread and
Truvada as pre-exposure prophylaxis and as topical microbicides. After grades
were assigned, Gilead announced a joint venture with Tibotec to develop a co-formulated
tablet containing rilpivirine/tenofovir/emtricitabine.
Demographics of clinical trials:
Gilead has made efforts to enroll
and retain women, people of color and people with HCV coinfection in its
trials, but the numbers enrolled are not representative of the demographics of
the epidemic.
Interactions with the HIV treatment community:
Gilead has met with the treatment activist community to obtain
input and recommendations on its clinical trial designs. This has usually,
though not always, occurred early enough to change protocols when necessary.
Gilead scientists and marketing executives are accessible via a
variety of avenues including regular meetings with ATAC. The company has its
own community advisory board that is consulted on protocol design and marketing
issues. Gilead responds in a timely manner to written correspondence.
Gilead consults with community members on trial designs and
development plans.
Access:
Gilead has a patient assistance
program (PAP) to facilitate access to its marketed medicines for those who
cannot afford them. It also has a co-pay assistance program for people with
private insurance who use Truvada, Emtriva, Viread, or Atripla, that will cover
co-pay costs whenever they exceed $50 per prescription, up to a maximum of $200
per prescription per month. This co-pay plan requires one of the largest
initial out-of-pocket patient contributions of all the existing programs but
BMS’s, which has the same criteria.
Drug access has been continued for
clinical trial participants until a drug is approved and other payers—or the
PAP—become available.
Gilead opened expanded access
programs prior to approval of its drugs. It has provided free drugs to the
NIH’s AIDS Clinical Trials Group (ACTG) and to other clinical research networks,
and recently supplied Truvada for a Kaposi’s sarcoma trial in resource-limited
settings in Africa.
Pricing:
Gilead has followed industry
precedent and has not priced new medications substantially higher than others
in the same class, though annual price increases taken for Viread have been
higher (roughly 11%) than any other HIV drug.
Gilead has shown a willingness to
consult with the community on pricing. Gilead has an agreement with the Fair
Pricing Coalition to freeze the price charged to state AIDS Drug Assistance
Programs until December 31, 2010, although a price increase was taken before
the 2008 agreement went into effect.
Gilead has priced co-formulations
or reformulations no higher than the combined price of the component drugs.
GlaxoSmithKline
Drugs:
Retrovir (zidovudine, AZT)
Epivir (lamivudine, 3TC)
Ziagen (abacavir)
Combivir (zidovudine/lamivudine)
Trizivir (abacavir/zidovudine/lamivudine)
Epzicom (abacavir/lamivudine)
Lexiva (fosamprenavir)
Pipeline:
GlaxoSmithKline (GSK) currently has
two integrase inhibitors in development, one of which is entering phase IIb
studies. It also recently acquired a second-generation non-nucleoside reverse
transcriptase inhibitor (NNRTI) from Idenix that is in phase II testing. GSK
does not currently have any experimental hepatitis drugs in human testing.
Demographics of clinical trials:
GSK has been conducting studies of
HIV drugs for longer than any other company. Early studies largely reflected
the demographics of the epidemic in the United States at the time. However as
the demographics of the epidemic have changed, women and people of color were
underrepresented in recent studies:
· HEAT study: 18% female, 36% African American, 20% Hispanic
· KLEAN study: 22% female, 31% African American, 8% Hispanic
· ARIES study: 17% female, 32% African American, 18% Hispanic
The majority of studies by
pharmaceutical companies do not have sufficient numbers of women and
racial/ethnic minorities to draw statistically significant conclusions about
the comparative efficacy and safety in these populations.
Interactions with the HIV treatment community:
At the time these grades were
assigned, GSK was not consulting with ATAC or members of the treatment activist
community in a manner that would allow adjustment to study protocols prior to
enrollment. After grades were assigned, GSK announced it was agreeing to a
community request to modify a trial protocol for a dose finding study of its
integrase inhibitor.
GSK does not have a formal
community advisory board. Instead, the company holds one annual meeting for a
mixed group of community educators and activists to present information about
its approved drugs and educational seminars about recent HIV science, treatment
education, and HIV-related social concerns. Though the company usually
discusses the results from recently completed trials and the status of research
on new drugs, these meetings have not allowed for input on trial design. GSK
has not formally met with the DDC in more than five years.
GSK has not included community
members on its safety monitoring boards.
Access:
GSK has a patient assistance
program (PAP) to facilitate access to its marketed medicines for those who
cannot afford them. GSK also has a co-pay assistance program.
Drug access has been continued for
clinical trial participants until a drug is approved and other payers—or the
PAP—become available.
Expanded access programs for its
experimental drugs were launched ranging from a few months prior to approval to
approximately one year prior to approval.
Pricing
GSK last set initial drug prices
with the approvals of Ziagen and Lexiva. On average, these drugs were priced
nearly one-third higher than existing drugs in their classes at the time of
approval. When Epzicom was launched its price was equivalent to the price of
Ziagen and Epivir combined. Average yearly price increases have been about 6%,
higher than for several other HIV drugs, but not as high as increases taken by
the worst offenders.
GSK has met with the Fair Pricing
Coalition prior to launching drugs and to discuss subsequent price increases.
GSK has priced co-formulations or
reformulations no more than the price of the combined price of the component
drugs.
Merck
Drugs:
Isentress (raltegravir)
Crixivan (indinavir)
Pipeline:
Merck is conducting clinical
research on second-generation integrase inhibitors, second-generation NNRTIs,
and protease inhibitors that do not require boosting. It has basic research
programs focusing on latency and persistence and a novel target called RNAseH;
it continues to work on an HIV vaccine; and it has filed with the FDA for
approval of the use of Gardasil for HPV in men.
Merck has an HCV protease inhibitor
and an HCV polymerase inhibitor in development.
Demographics of clinical trials:
Merck’s FDA approval trials for
Isentress included 12% female, 12% African American and 16% Hispanic
volunteers. No difference in safety and efficacy was reported in women or
people of color, though there were insufficient numbers to make statistically
significant conclusions for these populations.
Interactions with the HIV treatment community:
Merck regularly meets with the
treatment activist community, both with ATAC and through its standing advisory
board. It seeks input on clinical trial design early enough to change protocols
when necessary.
Merck has not included members of
the community on its safety monitoring boards.
Access:
Merck has a patient assistance
program (PAP) to facilitate access to its marketed medicines for those who
cannot afford them. The eligibility criterion for income is 500% of the federal
poverty level. The company has a co-pay reimbursement program that covers any
amount paid by patients over $30 and up to $400 per month for Isentress.
Drug access has been continued
for clinical trial participants until a drug is approved and other payers—or
the PAP—become available.
Merck launched an expanded access
program for Isentress early during its phase III trials.
Pricing:
Isentress was the first-in-class
integrase inhibitor. Merck followed the recommendations of the Fair Pricing
Coalition (FPC), pricing Isentress in line with the most recently marketed
protease inhibitor. Merck meets with the FPC prior and after drug approval in
regard to price increases.
Pfizer
Drugs:
Selzentry (maraviroc)
Viracept (nelfinavir)
Rescriptor (delavirdine)
Pipeline:
Pfizer has several HIV drugs in
development, including a second-generation NNRTI and a second-generation CCR5
antagonist, both in phase II trials, and a drug boosting agent in phase 1
trials.
Pfizer has several HCV compounds,
an HCV polymerase inhibitor (phase II) and a toll-like receptor 7 (TLR-7)
agonist in early development.
Demographics of clinical trials:
Pfizer’s MOTIVATE trials for
treatment experienced patients enrolled 11% women and 15% non-white
participants. For its Selzentry expanded access program (EAP), Pfizer recruited
physicians treating large numbers of women and people of color and provided
additional support to these sites to encourage participation. The EAP enrolled
approximately 20% women. The MERIT study in treatment-naive patients enrolled
approximately 28% women and 45% people of color.
Interactions with the HIV treatment community:
Pfizer has made its scientists,
marketing directors, and community liaisons accessible to the treatment
activist community at various phases of the drug development process and after
approval. Correspondence is provided in writing in a timely manner.
Pfizer has met with ATAC on a
regular basis. It regularly conducts advisory boards in the United States, Europe and internationally.
Community members have served on
safety monitoring boards and as reviewers of protocols and educational
materials.
Access:
Pfizer has a patient assistance
program to help with reimbursement for Selzentry and to provide information on
obtaining tropism testing. Pfizer does not currently offer co-pay assistance
for its HIV medications.
The maraviroc expanded access
program was initiated in a timely fashion, and clinical trial participants
obtained continued access to maraviroc through commercial channels, patient
assistance programs and roll-over studies (in certain locations).
Pricing:
Annual price increases for Pfizer’s
older Viracept (nelfinavir) and Rescriptor (delavirdine) have been low (~3%).
Pfizer set the price of Selzentry (maraviroc) around the price of the most
expensive protease inhibitors.
Pfizer has worked with and
continues to engage with the Fair Pricing Coalition on pricing.
Roche
Drugs:
Fuzeon (enfuvirtide)
Invirase (saquinavir)
Pipeline:
Roche has ended active research on
new HIV drugs, though it continues to market Fuzeon (enfuvirtide) and Invirase
(saquinavir). Roche is developing several HCV drugs, including an HCV protease
inhibitor, R7227, currently in phase I, in partnership with Intermune; an HCV
nucleoside polymerase inhibitor, R7128, currently in phase II, in partnership
with Pharmasset; and an HCV polymerase inhibitor in partnership with Metabasis.
Demographics of clinical trials:
The TORO trials for Fuzeon enrolled
less than 10% women and less than 11% non-white individuals; numbers too small
to define safety and efficacy in those populations with statistical certainty.
Interactions with the HIV treatment community:
Roche met with treatment activists
during the development of Fuzeon, but formally met with ATAC only about six
months prior to approval, by which time the Fuzeon protocols were well underway
and could not be substantially altered or improved. Roche currently engages in
only minimal HIV community relations activities. Roche meets frequently with
HCV treatment advocates.
Roche used patients as pawns in
their negotiations with state governments. Soon after the launch of Fuzeon,
Roche refused to expand its patient assistance program in states that declined
to add Fuzeon to their AIDS Drug Assistance Program (ADAP) formularies. All
state ADAP programs now offer Fuzeon.
Access:
Roche’s patient assistance program
(PAP) facilitates access to Fuzeon for those who cannot afford it.
The TORO trial participants had
access to the treatment after the study and up to the point that it could be
covered by third-party payers. The Fuzeon PAP was launched immediately after
the TORO trial ended, but expanded only in those states that covered the drug
through an ADAP program.
Pricing:
Upon its launch Fuzeon became the
highest-priced HIV drug in any class. Roche consulted with the Fair Pricing
Coalition prior to approval, but priced the drug far higher than the community
felt was fair or necessary.
Tibotec
Drugs:
Prezista (darunavir)
Intelence (etravirine)
Pipeline:
Tibotec has a number of HIV drugs
in development, including rilpivirine, a second-generation NNRTI that will
likely be the next HIV drug to receive FDA approval. Tibotec is also
researching a new HIV protease inhibitor, novel formulations of its existing
drugs and a new pharmacokinetic boosting agent.
The company is developing an HCV
protease inhibitor (telaprevir) in collaboration with Vertex and a
second-generation HCV protease inhibitor (TMC435) in collaboration with
Medivir.
The company has donated TMC120 for
development as a microbicide and is developing a novel anti-tuberculosis drug
for use in the developing world.
After grades were assigned, Tibotec
announced a joint venture with Gilead to develop a co-formulated tablet
containing rilpivirine/tenofovir/emtricitabine.
Demographics of clinical trials:
Tibotec has a slightly better than
average record for enrolling women and people of color in its FDA approval
trials:
· POWER 1, 2, and 3: approximately 12% women, 26% nonwhite
· DUET: approximately 10% women, 30% nonwhite
· TITAN: 25% women, 45% nonwhite
· ARTEMIS: 30% women, 60% nonwhite
As with other companies, Tibotec’s
trials for treatment-naive patients enrolled significantly more women and
people of color than trials for treatment-experienced people. The recently
completed GRACE study recruited 67% women and 84% people of color. Though the
FDA asked for a post market study in a diverse population Tibotec’s GRACE
design went further than the FDA required.
Interactions with the HIV treatment community:
Tibotec has sought extensive
consultation with the treatment activist community on drug development issues
and has sought community review of informed consent documents, trial protocols,
marketing materials and drug access policies. In some cases trial designs were
well advanced at the time the company sought community input, but in other
cases the company made timely requests for meaningful input about research
direction and broad design issues. In one case Tibotec proceeded with the DUET
study despite activist warnings that it could provide some participants with
less than the minimum of two active drugs required for reliable HIV
suppression.
Tibotec uses community advisory
boards in an ad-hoc fashion, determined by its objectives and the expertise
sought. It meets with ATAC on a regular basis.
Tibotec has included community
members on most of its safety monitoring boards.
Access:
Tibotec’s patient assistance
program (PAP) facilitates access to its marketed medicines for those who cannot
afford them. Tibotec’s co-pay assistance program covers the first 80% of
out-of-pocket co-pay expenses up to $100 per Tibotec product per month; this is
a more generous program than that of some companies, but less generous than
others. The PAP and co-pay programs are featured prominently on company
websites and in other marketing materials.
Tibotec launched large, broadly-available
expanded access programs for its experimental drugs.
Drug access has been continued for
clinical trial participants until a drug is approved and other payers—or the
PAP—become available.
Tibotec has provided drugs to
clinical trials networks (including royalty-free drug donations for microbicide
development) and company executives recently advocated with parent company
Johnson & Johnson to provide Doxil (doxorubicin) for a Kaposi’s sarcoma
cancer trial in a resource-poor setting.
Pricing:
Tibotec has priced its drugs
somewhat lower or equivalent to other drugs in respective classes, even though
there was evidence that Tibotec’s drugs were superior to those of the
competition in potency or tolerability. The company has responded to
price-freeze agreements and price increases have been average for this market.
Tibotec meets regularly with the
Fair Pricing Coalition and has honored its commitments on restrained pricing.
The company has worked with state
AIDS Drug Assistance and Medicaid programs to keep new dosage forms of its
products cost-neutral for these payers.