Counting the pills
The basic criteria for an efficient contraceptive
drug are reliability, effectiveness and reversibilty. In the absence
of a wholly satisfactory contraceptive for women, and none at all
for men, the market will always remain hungry for the perfect pill.
Aashruti Kak traces the moves of the contraceptive market
the time when the first contraceptive pill found its way in the world market
till now, there have been a surplus of contraceptives available-- injectables,
vaccines, patches, emergency contraception, spermatocides, implants, pills and
others (condoms, vaginal rings and intrauterine devices)--giving women an array
Globally and domestically, the market for contraceptives
comprises hormone-based products, barrier products, intra-uterine device (IUD)
products and other methods. Joy Chatterjee, Assistant Product Manager--Product
Management Team, Mankind Pharma, says, "Hormone-based products, being a
publicly funded sector, form the largest sector, and has outdone barrier products,
which comprised the largest sector in 2004. The former continues to perform
well, particularly with oral contraceptives, while the latter is currently experiencing
difficulties in terms of deflationary pressure on prices, which is affecting
According to the report titled ContraceptivesA Global Strategic Business
Report published by Global Industry Analysts, the world market for contraceptive
implants/injections is forecast to grow the strongest in Asia-Pacific over the
period 2000 to 2015, and will reach $359.60 million by the year 2015. The world
oral contraceptives market is dominated by the United States and Europe with
a combined 75.82 percent share estimated in the year 2007.
While India has the second-largest population in the world, the market for hormonal
contraceptives is small, because of a low contraceptive-prevalence rate (CPR)
(42.8 percent) and a high reliance to sterilisation. Female and male sterilisation
comprises more than 80 percent of contraceptive use, states an assessment report
produced in March 2006 by the United States Agency for International Development
(USAID). In addition, the report states that there has been little growth in
the CPR; the majority of what growth there has been involves sterilisation,
resulting in a flat market for hormonal contraceptives.
Further, the report states that the Indian hormonal-contraceptive market is
bifurcated into high-priced products, dominated by multinational corporations'
(MNCs) brands, and a low-end market, dominated by products that are free or
subsidised by the government or site management organisations (SMOs).
What is steering the market?
at this contraceptive market, education, income and lifestyle of age group
of 18 to 40 years are the major growth drivers in India. Contemporary mindset
of different ethnic and religious age groups and awareness of male contraceptives
is also an issue in acceptance"
- Dr R B Smarta
Interlink Marketing Consultancy
The idea of planned parenthood had already caught up with
the Indian population, but now it is on a fast track as education levels are
rising and people are becoming more career oriented and have prioritised their
lives over conception.
Also, society is changing and people are becoming sexually
active at an earlier age. This impacts the teenage pregnancy rate, and also
the occurrences of sexually transmitted infections (STIs), which are increasing
at alarming rates. "Looking at this contraceptive market, education, income
and lifestyle of age group of 18 to 40 years are the major growth drivers in
India. Contemporary mindset of different ethnic and religious age groups and
awareness of male contraceptives is also an issue in acceptance," says
Dr R B Smarta, Managing Director, Interlink Marketing Consultancy.
The ease with which a method is used by consumers also has one of the biggest
influences on the market world over. The most comfortable mode is through oral
administration, and hence, oral pills are one of the most widely used contraceptive
methods across the world. Because injectables are inconvenient to use and IUDs
are not affordable for all and may have other misgivings attached to them, they
fall back in the list. Another method that seems effortless, and hence, appealing
is a contraceptive patch. In India, Ortho Evra patch, a Johnson&Johnson
product is available in this category.
Playing the game
be accepted in the long run, a method has to be reliable, safe and reversible.
Of the methods that are over 99 percent reliablepills, tubectomy and
IUDsmost have significant effects on the woman's health. If new methods
contraception were to be made available, men can be encouraged to try them"
- Joy Chatterjee
Assistant Product ManagerProduct Management Team
The leading global players operating in the industry include
Ansell, Barr Pharmaceuticals, Bayer Schering Pharma, Female Health Company,
Church & Dwight, Conceptus, Condomi Health International, Ortho-McNeil Pharmaceutical,
Schering-Plough, Organon USA, SSL International, Wyeth, Warner Chilcott, and
Pfizer among others.
Indian manufacturers of generic hormonal contraceptives (oral contraceptive
pills (OCPs)), emergency contraception (EC), and injectable contraceptives (ICs)
and intrauterine devices (IUDs) have a prominent role in supplying products
to family-planning programmes in many developing countries. The buyers for these
programmes are governmental or multilateral institutions, such as the United
Nations Population Fund (UNFPA); multilateral and bilateral donors; ministries
of health; and social-marketing organisations.
In India, large and small players are Hindustan Latex, TTK-LIG,
TTK-Biomed, Contech Devices, Cupid Rubber, Polar, JK Chemicals, London Rubber
Company, Win-Medicare, Famy Care, Pregna International, Pfizer, GlaxoSmithKline,
Organon India, Cipla, Mankind Pharma, Natco Pharma among others.
Pfizer imports the only injectable marketed in India, Depo-Provera (depot medroxyprogesterone
acetate--DMPA). ICs are not produced in India. Although Upjohn introduced DMPA
initially, following a series of mergers, Pfizer took it over. The report by
USAID states that Indian manufacturers have an interest in this product category,
however, and are preparing to produce and/or market DMPA domestically and overseas.
Pfizer's DMPA dominates the limited market for this product, but it is embroiled
in legal battles. German Remedies markets OCP brands Duoloton-L and Triquilar,
with the latter being the only triphasic oral contraceptive pill in the market.
The company previously marketed Net-En (nortesteone enenthate), a two-month
injectable. It also discontinued marketing ECEE-2, its EC brand. Organon markets
Novelon and Femilon OCPs and the IUD Multiload. Internationally, Organon markets
Megestron, a two-month injectable. Wyeth markets several brands of OCPs--Ovral-L,
Ovral-G, and the low-dose Loette. GSK has a low dose pill, Elogen (desogestrel
and ethinylestradiol), and Zerogen (progesterone only pill).
"Mankind has Unwanted-72 ie, levonorgestril 1.5 mg tablet in the market.
Competing with it are I-pill, pill-72 by Cipla, and Norlevo by Win Medicare.
Mankind also launched Unwanted-21 days, which is an oral contraceptive pill
for regular day to day use," says Chatterjee. Natco Pharma launched 'Tarana'
in June 2007, the first generic version of Yasmine, which is an international
brand from Bayer. This was followed by Cipla's announcement in November last
year launching a new generation oral contraceptive pill 'Crescenta', which is
a prescription drug (also a generic version of Yasmine) without regular side
effects, and will be competing with Natco's Tarana.
A history of controversies
ICs have had a troubled past in India. While it has long been known that DMPA
causes bone loss, it was discovered that osteoporotic effects of the injection
grow worse the longer DMPA is administered and they may last long after the
injections are stopped. For this reason, on November 17, 2004, the United States
Food and Drug Administration (FDA) and Pfizer agreed to put a black-box warning
on DMPA's label. ICs are associated with irregular bleeding and amenorrhea,
which are not culturally accepted in India and are a serious barrier to its
Another OTC medical abortion pill RU486, allowed by the Ministry of Health and
Family Welfare in 2002, was shrouded in controversies as it did away with the
need for medical advice to terminate pregnancy. Similar is the case with contraceptive
patches, as Ortho Evra (J&J) too is submerged in legal battles as the patch
has serious side-effects. So much so, that a few months ago the FDA upgraded
the warning on the labelling to include results of an epidemiology study that
found that Ortho-Evra users were at higher risk of developing serious blood
clots, also known as venous thromboembolism (VTE), than women using birth control
|RISUG is composed of styrene maleic anhydride (SMA)
complexed with the solvent dimethylsulfoxide (DMSO). It has two contraceptive
effects--partial blockage of the vasa deferentia and disruption of the sperm
that pass through it.
RISUG ruptures the membranes of the sperms by stressing
their ion exchange mechanisms. The membrane carries molecular keys that
are needed to attach to an egg, and packets of enzymes that are needed
to dissolve the outer coating of an egg. Without those keys or enzymes,
the sperms are functionally infertile.
Primate studies have shown that RISUG is readily reversible,
but reversal has not yet been tested officially in humans. The compound
can be removed by flushing the vasa deferentia with an injection.
Slight swelling of the testes was reported in the clinical
trials with no associated pain, which resolved within two weeks of the
injection with no treatment. RISUG does not cause the common side effects
of a vasectomy--granulomas and an autoimmune response. RISUG does not
cause these side effects because it does not fully block the vasa deferentia.
For 'her' and 'him'?
There are certain stereotypes about men which are generally a source of skepticism
about the practicability of new male contraceptives. Many believe that men are
too irresponsible or untrustworthy to participate in family planning, while
others may believe that men will not use a method of contraception that requires
trips to the doctor or uncomfortable injections. This is one reason why most
drug R&D in this segment is targeted towards women. However, according to
Chatterjee, there are studies that show that men want access to better contraceptives.
For instance, in a study of British men in 1998 featured in the British Journal
of Family Planning, 80 percent men placed a hypothetical male pill as one of
their top three contraceptive choices.
"If men are presented with safe and reliable, and most importantly, a reversible
contraception, it is unlikely that men will reject a method just because it
involves a drug or a medical procedure," says Chatterjee. He continues,
"As far as women are concerned, there is still no entirely satisfactory
long-term female contraceptive, because to be accepted in the long run, a method
has to be reliable, safe and reversible. Of the methods that are over 99 percent
reliable--pills, tubectomy and IUDs--most have significant effects on the woman's
health. If new methods of male contraception were to be made available, men
can be encouraged to try them."
So, if men are ready, what is preventing the pharma industry from developing
a male contraceptive? The truth is that many of these methods have little profit
potential and are not being pursued or publicised by pharma companies.
There is always a possibility that a drug used for a particular indication can
be effective in other diseases as well. Such drugs have come to light over years
of search for an appropriate male contraceptive drug, but either they have been
researched upon to an extent and aborted, have irreversible effects or have
not been pursued at all, even by the same companies that own those drugs. For
instance, Nifedipine, which is a calcium channel blocker used to treat high
blood pressure and migraine, was tested for its contraceptive effects and proved
in the year 2000 by researchers in New York. It was found that the drug mechanism
produced infertility within one month of taking the drug, which could be reversed
within three months of discontinuing it. Irrespective of this revelation, the
drug dropped off the contraceptive therapy radar..The drug is manufactured by
six major pharma companies, including Pfizer (Procardia), Aventis (Cardizem)
and Bayer (Adalat).
One reason why that may be the case is that manufacturers may not want men to
know about nifedipine's contraceptive effects or they could easily lose market
share in future hypertension prescriptions if the controversy were made public.
Second, patents on formulation of nifedipine have expired. Other drug companies
have begun manufacturing generic nifedipine, undercutting the drug's price;
hence, large drug companies have little incentive to invest in developing it
as a contraceptive.
From the most promising of all discoveries, Reversible Inhibition of Spermatozoa
Under Guidance (RISUG-developed by Professor Sujoy Guha from Indian Institute
of Technology) has so far shown the most potential in the hunt for an effective
male contraceptive mechanism. "RISUG is an injectable compound that partially
blocks the vas deferentia (tubes that carry sperm), providing effective contraception
for up to 10 years per dose. It is effective immediately, has few side effects,
and has proven to be reversible in primate studies," says Chatterjee. This
contraceptive has completed phase I and II clinical trials in India (Guha 1997).
RISUG entered phase III clinical trials in India in 2002 but was discontinued
due to certain concerns and hang ups regarding the validation of toxicological
tests the clinical trials were stalled. In 2007, Marksans, which holds a manufacturing
agreement with RISUG's inventor and the Government, was able to deliver a batch
of RISUG produced to the World Health Organization's Good Manufacturing Practice
(WHO GMP) standards, to be used in clinical trials. Once the process and its
efficiency minus the side effects are proved, it will open an entire new market
of contraceptives for men. Effective drugs will come and go. The fact remains
that unless there is a ready market for a male contraceptive pill, pharma companies
will not make any moves. What we really need are more studies on all experimental
male contraceptive methods known so far. Only once the R&D is on the way
will we hit upon the actual worth of these drugs.