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

From 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 of choices.

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 value levels."

According to the report titled Contraceptives—A 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?

"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" - Dr R B Smarta Managing Director 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

"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" - Joy Chatterjee Assistant Product Manager—Product Management Team Mankind Pharma

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 use.

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 pills.

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.

RISUG

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.

aashruti.kak@expressindia.com